Skin Infections, infestations and other skin conditions

Seborrheic keratoses (SKs) are very common benign epithelial skin tumors encountered in the adult population. Seborrheic Keratosis is a skin condition in which there is brown to black color skin gowth which is slightly raised. It originates in the epidermis, and a proliferation of immature keratinocytes is present.

 

Seborrhoeic keratosis (or seborrheic keratosis) is also called basal cell papilloma, senile wart, brown wart, wisdom wart, or barnacle.  The descriptive term, benign keratosis, is a broader term that is used to include the following related scaly skin lesions:

  • Seborrhoeic keratosis 
  • Solar lentigo
  • Lichen planus-like keratosis (which arises from a seborrhoeic keratosis or a solar lentigo).
 

Seborrheic keratoses are harmless and not contagious. They don't need treatment, but you may decide to have them removed if they become irritated by clothing or you don't like how they look.

 

The name is misleading, because they are not limited to a seborrhoeic distribution (scalp, mid-face, chest, upper back) as in seborrhoeic dermatitis, nor are they formed from sebaceous glands, as is the case with sebaceous hyperplasia, nor are they associated with sebum — which is greasy.

 

The precise cause of seborrhoeic keratoses is not known.

Seborrhoeic keratoses are considered degenerative in nature. As time goes by, seborrhoeic keratoses become more numerous. Some people inherit a tendency to develop a very large number of them. The various observations seen in seborrheic keratosis are:

  • Eruptive seborrhoeic keratoses can follow sunburn or dermatitis.
  • Skin friction may be the reason they appear in body folds.
  • Viral cause (eg human papillomavirus)
  • Stable and clonal mutations or activation of FRFR3, PIK3CA, RAS, AKT1 and EGFR genes are found in seborrhoeic keratoses.
  • Seborrhoeic keratosis can arise from solar lentigo.
  • FRFR3 mutations also arise in solar lentigines. These mutations are associated with increased age and location on the head and neck, suggesting a role of ultraviolet radiation in these lesions.
  • Seborrhoeic keratoses do not harbour tumour suppressor gene mutations.
  • Epidermal growth factor receptor inhibitors (used to treat cancer) often result in an increase in verrucal (warty) keratoses.

Variants of seborrhoeic keratoses

Variants of seborrhoeic keratoses include:

  • Solar lentigo: flat circumscribed pigmented patches in sun-exposed sites
  • Dermatosis papulosa nigra: small, pedunculated and heavily pigmented seborrhoeic keratoses on head and neck of darker-skinned individuals
  • Stucco keratoses: grey, white or yellow papules on the lower extremities
  • Inverted follicular keratosis
  • Large cell acanthoma
  • Lichenoid keratosis: an inflammatory phase preceding involution of some seborrhoeic keratoses and solar lentigines.

 

Diagnosis of Seborrheic Keratosis

It is difficult to identify the lesion of Seborrheic Keratosis by naked eye is difficult. The lesion is confused with warts, (pigmented) basal cell, carcinoma, pigmented Bowen’s disease, (verrucous) melanoma, extramammary Paget’s disease, common warts, acanthosis nigricans, and Seborrheic Keratosis like lesions localized to tattoo1.

Although most Seborrheic Keratosis have a maximum diameter of less than 4 cm, sometimes giant lesions develop that raise some possible differential diagnoses, including Buschke–Löwenstein tumors1.

The diagnosis of Seborrheic keratosis can be made with confidence with a high resolution dermascope, through which the lesions of Seborrheic keratosis exhibit the typical dermoscopic findings of fissures and ridges, hairpin vessels with white halo, comedo-like openings, and milia-like cysts.The histopathologic counterparts of the dermoscopic findings are papillomatous epidermis, enlarged dermal capillaries, pseudo-horn cysts, and intraepidermal cysts. Dermoscopy is of practical
value in differentiating Seborrheic keratosis from malignant melanoma1.

Diagnostic findings on dermascopy shows a disordered structure with multiple orange or brown clods (due to keratin in skin surface crevices), white milia-like clods, and curved thick ridges and furrows forming a brain-like or cerebriform pattern.

 

Dermoscopy showing fissures and ridges, sharp demarcation, and moth-eaten border5

Dermoscopy findings in Seborrheic keratosis 5
1 Comedo like openings
2 Fissures and Ridges
3   Millia like cysts
4  Sharp demarcation and network like structure
5 Moth eaten border
6 Fingerprint structures
7 Hair pin blood vessels

Seborrheic Keratosis of the genitalia is a rare entity13, 14. It has been frequently mistaken as genital warts and differentiation is made only on histopathology12.There have been reports of Human papilloma virus in the lesions of Seborrheic keratosis. Seborrheic keratoses situated in the anogenital region often resemble condylomata acuminata, clinically and histopathologically, yet they are benign neoplasms of unknown cause, in contrast to condylomata acuminata, which are hyperplasias induced by human papillomavirus (HPV). To put an end to this controversy now it is postulated that lesions which have  but these “Seborrheic Keratoses” That Contain Human Papillomavirus Are Condylomata Acuminata6. A pathogenic relationship between HPV and genital SK by showing: 1) a high rate of virus detection in these lesions, with a strong predilection for HPV6, and 2) scarcity of genital HPV types in most of the remaining non-SK cutaneous genital lesions and in the extragenital Seborrheic Keratosis. HPV cannot be found in a minority of genital Seborrheic Keratosis using highly sensitive techniques, and therefore, other presently unknown factors may also be implied in the pathogenesis of these lesions8.Thus Genital seborrheic keratoses are human papillomavirus-related lesions8. The genital lesions rather be called as seborrheic keratosis like lesions because of their relation to low risk human papilloma virus. Genital seborrheic keratosis is invariably associated with HPV infection8, 9, 13.

 

Symptoms

A seborrheic keratosis usually looks like a waxy or wartlike growth. It typically appears on the face, chest, shoulders, back, spine and groin. Seborrhoeic keratoses can arise on any area of skin, with the exception of palms and soles. They do not arise from mucous membranes. You may develop a single growth, though multiple growths are more common. They appear to stick on to the skin surface.

A seborrheic keratosis:

  • Ranges in color from light tan to brown or black, Skin coloured, yellow, grey, light brown, dark brown, black or mixed colours
  • Is round or oval shaped
  • Has a characteristic "pasted on" look
  • Is flat or slightly raised with a scaly surface, Flat or raised papule or plaque, Smooth, waxy or warty surface
  • Ranges in size from very small to more than 1 inch (2.5 centimeters) across (1 mm to several cm in diameter)
  • May itch

 

 

 

Medical Management

Ammonium lactate (Lacsoft cream) and alpha hydroxy acids have been reported to reduce the height of seborrheic keratoses.  Superficial lesions can be treated by carefully applying pure trichloroacetic acid and repeating if the full thickness is not removed on the first treatment.

The US Food and Drug Administration (FDA) approved a concentrated hydrogen peroxide 40% solution (Eskata) for adults with raised seborrheic keratosis. The solution is available within an applicator pen and is administered in a medical office setting by a healthcare professional4.HP40 may act not only through its direct oxidation of organic tissues, generation of reactive oxygen species, and local lipid peroxidation but also by the generation of local concentrations of oxygen that are toxic to Seborrheic Keratosis cells7, 10.

 

Surgical Management

 

Methods used to remove seborrhoeic keratoses include:

  • Cryotherapy (liquid nitrogen) for thinner lesions with carbon dioxide (dry ice) or liquid nitrogen,
  • Curettage and/or electrocautery / Electrodesiccation / electrodesiccation and curettage / curettage alone (If a biopsy is not desired).
  • Ablative laser surgery / dermabrasion surgery
  • Shave biopsy (shaving off with a scalpel) - Shave biopsy or excision using a scalpel, The shave biopsy provides histologic material for accurate diagnosis and removes the lesion in a cosmetically acceptable manner at the same time. After a shave biopsy is obtained, a curette can be employed to smooth and remove any remaining keratotic material.
  • Focal chemical peel with trichloracetic acid

 

Long-Term Monitoring

Follow-up for patients with multiple seborrheic keratoses is important because malignant tumors can develop elsewhere on the body (or rarely within a seborrheic keratosis). New seborrheic keratoses develop as people age. The Sign of Leser–Trélat is a rare finding of sudden eruption of seborrhoeic keratoses associated with malignancies, like gastrointestinal adenocarcinoma or melanoma15,16.

 

Differential Diagnosis of Seborrheic keratosis11

  • Acrochordon
  • Acrokeratosis Verruciformis of Hopf
  • Actinic Keratosis
  • Arsenical Keratosis
  • Basal Cell Carcinoma
  • Bowen Disease
  • Bowenoid Papulosis
  • Confluent and Reticulated Papillomatosis
  • Cutaneous Horn
  • Cutaneous Manifestations of HIV
  • Cutaneous Melanoma
  • Cutaneous Squamous Cell Carcinoma
  • Dermatosis Papulosa Nigra
  • Epidermal Nevus Syndrome
  • Epidermodysplasia Verruciformis
  • Erythroplasia of Queyrat (Bowen Disease of the Glans Penis)
  • Genital Warts
  • Guttate Psoriasis
  • Lentigo
  • Melanocytic Nevi
  • Nevus Sebaceus
  • Nongenital Warts
  • Pemphigus Erythematosus
  • Plaque Psoriasis
  • Premalignant Fibroepithelial Tumor (Pinkus Tumor)
  • Prurigo Nodularis
  • Sign of Leser-Trelat
  • Stucco Keratosis
  • Warty Dyskeratoma

 

References

  1. Wollina U. Recent advances in managing and understanding seborrheic keratosis. F1000Res. 2019 Aug 28;8:F1000 Faculty Rev-1520. doi: 10.12688/f1000research.18983.1. PMID: 31508199; PMCID: PMC6719672.
  2. Fernandes KAP, Martinez DCS, Nobre AB, Campos-do-Carmo G. Collision tumor: pigmented Bowen's disease and seborrheic keratosis. An Bras Dermatol. 2018 Sep-Oct;93(5):737-739. doi: 10.1590/abd1806-4841.20187117. PMID: 30156629; PMCID: PMC6106659.
  3. Salah B, Mahseeri M, Al-Ali Z, Gaith A, Aldwan T, Al-Rawashdeh B. Giant perianal Seborrheic keratosis: A case report. Int J Surg Case Rep. 2018;51:296-301. doi: 10.1016/j.ijscr.2018.09.001. Epub 2018 Sep 12. PMID: 30243263; PMCID: PMC6148732.
  4. Robertson S, Franko J. Hydrogen Peroxide 40% (Eskata) for Seborrheic Keratosis. Am Fam Physician. 2019 Nov 15;100(10):643-644. PMID: 31730314.
  5. Alapatt GF, Sukumar D, Bhat MR. A Clinicopathological and Dermoscopic Correlation of Seborrheic Keratosis. Indian J Dermatol. 2016 Nov-Dec;61(6):622-627. doi: 10.4103/0019-5154.193667. PMID: 27904179; PMCID: PMC5122276.
  6. Li, Juan M.D.; Ackerman, A. Bernard M.D. “Seborrheic Keratoses” That Contain Human Papillomavirus Are Condylomata Acuminata, The American Journal of Dermatopathology: August 1994 - Volume 16 - Issue 4 - p 398-405 (abstract).
  7. Baumann LS, Blauvelt A, Draelos ZD, Kempers SE, Lupo MP, Schlessinger J, Smith SR, Wilson DC, Bradshaw M, Estes E, Shanler SD. Safety and efficacy of hydrogen peroxide topical solution, 40%(w/w) in patients with seborrheic keratoses: results from two identical, randomized, double-blind, placebo-controlled, phase 3 studies (A-101-SEBK-301/302) Journal of the American Academy of Dermatology. Volume 79, Issue 5, November 2018, Pages 869-877.
  8. Tardío JC, Bancalari E, Moreno A, Martín-Fragueiro LM. Genital seborrheic keratoses are human papillomavirus-related lesions. A linear array genotyping test study. APMIS. 2012 Jun;120(6):477-83. doi: 10.1111/j.1600-0463.2011.02853.x. Epub 2012 Jan 12. (abstract).
  9. Talia KL, McCluggage WG. Seborrheic Keratosis-like Lesions of the Cervix and Vagina: Report of a New Entity Possibly Related to Low-risk Human Papillomavirus Infection. Am J Surg Pathol. 2017 Apr;41(4):517-524. PMID: 27792064. (Abstract).
  10. Wollina U. Seborrheic Keratoses - The Most Common Benign Skin Tumor of Humans. Clinical presentation and an update on pathogenesis and treatment options. Open Access Maced J Med Sci. 2018;6(11):2270-2275. Published 2018 Nov 23. doi:10.3889/oamjms.2018.460
  11.  emedicine.medscape.com Seborrheic Keratosis by Arthur K Balin, MD, Medical Director, The Sally Balin Medical Center for Dermatology.
  12. Sudhakar N, Venkatesan S, Mohanasundari PS, Thilagavathy S, Elangovan P. Seborrheic keratosis over genitalia masquerading as Buschke Lowenstein tumor. Indian J Sex Transm Dis AIDS. 2015 Jan-Jun;36(1):77-9. doi: 10.4103/0253-7184.156736. PMID: 26392661; PMCID: PMC4555906.
  13. Part M, Svecová D, Brezová D, Breza J. Giant seborrheic keratoses on penis. J Sex Med. 2014 Dec;11(12):3119-22. doi: 10.1111/jsm.12676. Epub 2014 Aug 19. PMID: 25135108. (Abstract).
  14. Thakur JS, Thakur A, Chauhan CG, Diwana VK, Chauhan DC. Giant pedunculated seborrheic keratosis of penis. Indian J Dermatol. 2008 Jan;53(1):37-8. doi: 10.4103/0019-5154.39743. PMID: 19967020; PMCID: PMC2784587.
  15. Chakradeo K, Narsinghpura K, Ekladious A. Sign of Leser-Trélat. BMJ Case Rep. 2016;2016:bcr2016215316. Published 2016 Apr 8. doi:10.1136/bcr-2016-215316.
  16. Gori N, Esposito I, Del Regno L, D'Amore A, Peris K, Di Stefani A. Leser-Trélat sign as a rare manifestation of cutaneous melanoma. Dermatol Reports. 2020;12(1):8665. Published 2020 Jul 6. doi:10.4081/dr.2020.8665
 

GENITAL WARTS

 

A wart is a small growth with a rough texture that can appear anywhere on the body, it looks like a small cauliflower. All warts are caused by Human Papilloma Virus (HPV).

 

 

Genital Warts-Standard Treatment Guidelines

Warts occuring on external genitalia are called genital warts. External genital warts are also known as condylomata acuminata. They are one of the most common forms of sexually transmitted diseases. Genital warts are single or multiple soft, painless, flat, papular, or pedunculated growths which appear around the anus, vulvovaginal area, penis, urethra and perineum. May also appear as keratinized papules. Common sites are

  • Men: under the foreskin, on the shaft
  • Women: around the introitus
  • Both: On the anogenital epithelium,within the anogenital tract.

High-risk human papillomaviruses (HPV 16 & 18 serotypes) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. 

They are caused by a small DNA virus, a papillomavirus belonging to the papovavirus group, which cannot be cultured. Genital warts differ from skin warts histologically and antigenically. Genital warts are nearly always transmitted by sexual contact; autoinoculation from hand to genitals is unusual. The infectivity of sexually acquired warts is about 60%; the incubation period is long, varying from two weeks to eight months.

Genital warts are often asymptomatic and painless. Patients may give a history of suddenly noticing them or noticing them only once their sexual contact has acquired them. Women are more likely to be unaware of warts because it is harder for them to examine their genitalia. Warts flourish in warm, moist conditions, particularly if a discharge or other infections are present.

In men they may be found on the glans and shaft of the penis, prepuce, fraenum and coronal sulcus, urethral meatus, scrotum,
anus, and rectum. Even though anal warts usually occur after anal intercourse they may occur without this. In women the commonest site of infection is the introitus and vulva, but warts may also affect the vagina and (as flat warts) the cervix. Other infected sites may be the perineum, anus, and rectum.

 

Cutaneous (skin) HPV types

Most HPV types are called cutaneous because they cause warts on the skin, such as on the arms, chest, hands, and feet. These are common warts, not genital warts.

 

Mucosal (Genital or Anogenital) HPV types

The other HPV types are considered mucosal types because they invade and live in cells on mucosal surfaces. The mucosal HPV types are also called genital (or anogenital) HPV types because they often affect the anal and genital area. These types can also infect the lining of the mouth and throat.   Mucosal HPV types generally don’t grow in the skin or parts of the body other than the mucosal surfaces.

 

Low-risk mucosal (genital) HPV types:

HPV types that tend to cause warts and rarely cause cancer are called low-risk types. Low-risk genital HPV infection can cause cauliflower-shaped warts on or around the genitals and anus of both men and women. In women, warts may appear in areas that aren’t always noticed, such as the cervix and vagina.

 

High-risk mucosal (genital) HPV types:

HPV types that can cause cancer are called high-risk types. These types have been linked to certain cancers in both men and women. Doctors worry about the cell changes and pre-cancers these types cause because they are more likely to grow into cancers over time.

Ministry of Health and Family Welfare, Government of India has issued the Standard Treatment Guidelines for Genital Warts. Following are the major recommendations :

Read more at Medical Dialogues: Genital Warts-Standard Treatment Guidelines http://speciality.medicaldialogues.in/genital-warts-standard-treatment-guidelines/

 

Mucosal (genital) HPV is spread mainly by direct skin-to-skin contact during vaginal, oral, or anal sexual activity. It’s not spread through blood or body fluids. It can be spread even when an infected person has no visible signs or symptoms.

Anyone who has had sexual contact can get HPV, even if it was only with only one person, but infections are more likely in people who have had many sex partners. 

The virus can also be spread by genital contact without sex, but this is not common. Oral-genital and hand-genital spread of some genital HPV types have been reported.

You DO NOT get HPV from:

  • Toilet seats
  • Hugging or holding hands
  • Swimming in pools or hot tubs
  • Sharing food or utensils
  • Being unclean

 

Causative organism

  • Caused by Human Papilloma virus (HPV) Type 6 or 11 (90% cases).
  • HPV types 16, 18, 31, 33, and 35 found occasionally and associated with high-grade intraepithelial neoplasia.
  • HPV is a highly contagious virus and is transmitted predominantly through oral, anal, and genital sexual contact
  • Sexual contact with an HPV-infected individual results in a 75-percent chance of contracting the virus and developing condylomata acuminata.
  • HPV types 6 and 11 rarely give rise to cervical cancers and are thus considered low-risk subtypes. Infection by these genotypes is responsible for 90 percent of the cases of genital wart formation. In contrast, HPV types 16 and 18 are strongly associated with cervical dysplasia and are therefore considered to be high risk, oncogenic subtypes. Evidence for infection by these genotypes is found in up to 70 percent of squamous cell carcinomas (SCC) of the cervix. Human Papilloma Virus (HPV) types 31, 33, 45, 51, 52, 56, 58, and 59 are typically thought to be of intermediate risk since they are often found in association with squamous neoplasms, but have been rarely linked to cervical Squamous cell cancer.
  • Patients with condylomata Acuminata may be infected simultaneously by multiple HPV strains.
  • HPV is a group of nonenveloped, double-stranded deoxyribonucleic acid (DNA) viruses belonging to the family Papovaviridae.
  • Viral replication is restricted to the basal cell layer of surface tissues. The virus will penetrate both the cutaneous and mucosal epithelium in search of the appropriate cellular host. It will subsequently invade and infect the basal keratinocytes of the epidermis. The mucosa can be infected anywhere along the genital tract, including the vulva, vagina, cervix, and perianal regions in females as well as the penile shaft, scrotum, periurethral, and perianal regions in males. Infected regions will be marked by a proliferation of viral DNA and the formation of a warty papule or plaque.
  • Low-risk HPV subtypes will remain separate from the host cell DNA and thus undergo replication independently. In contrast, high-risk HPV subtypes will incorporate their DNA directly into the host cell’s genetic material. The integration of viral and host cell DNA often results in the dysregulation and uncontrolled activation of the E6 and E7 genes, which promotes the transcription of oncoproteins. These will bind and inactivate tumor suppressor genes p53 and Rb, leading to increased cell proliferation and a greater risk of malignant progression
  • Condylomata Acuminata may increase in number and size or, alternatively, undergo a spontaneous regression. Approximately 30 percent of all warts will regress within the first four months of infection. Unfortunately, the majority of genital warts will recur within three months of infection, even after undergoing the appropriate treatments. Significant risk factors for long-term wart persistence include host immunosuppression, infection with high-risk HPV subtypes, and an older patient age. Conversely, the presence of CD4+ lymphocytes in the dermis and the epidermis is generally thought to be associated with elevated rates of spontaneous regression, highlighting the critical role played by the immune system in determining the course of viral infection.

 

Clinical Presentation (Signs and Symptoms)

  • Once infected with HPV, the virus typically requires an incubation period ranging anywhere from 3 weeks to 8 months prior to clinical manifestation.
  • Physical symptoms begin approximately 2 to 3 months after initial contact. The virus, however, is also capable of lying dormant within epithelial cells for prolonged periods of time. Infection may thus persist undetected for the duration of an individual’s lifetime with no manifestation of clinically apparent warts
  • The manifestation of the Human Papilloma virus (HPV) is development of the viral warts. These warts are usually asymptomatic but depending on the size and anatomic location, can be painful or pruritic.
  • Genital warts typically present on the moist tissues of the anogenital area, although they may occasionally develop in the mouth or the throat after oral sexual contact with an infected partner. Condylomata Acuminata have a highly variable appearance and may be flat, dome-shaped, cauliflower-shaped, or pedunculated.
  • Genital Warts can persent individually, as a solitary keratotic papule or plaque, but are more frequently found in large clusters. Often genital warts begin as small, nondistinctive 1 to 2mm flesh-colored papules on the skin and may retain this presentation for the duration of the infection. Alternatively, Condylomata Acuminata may grow as large as several inches in diameter, leading to the painful intercourse. The warty contour may also vary in color and appearance, ranging from white to pink, purple, red, or brown and from flat to cerebriform or verrucous.
  • Lesions are rarely considered to be painful; however, they are often associated with severe discomfort, burning, and pruritis. Moreover, larger lesions may be subject to bleeding and irritation upon contact with clothing or during sexual intercourse.
  • Both low-risk (subtypes 6 and 11) and high-risk (subtypes 16 and 18) HPV subtypes have also been associated with the very low-grade, well-differentiated squamous cell carcinoma known as verrucous carcinoma (VC). Verrucous carcinoma is divided into clinico-pathological types based on the anatomic area of involvement: oral florid papillomatosis (oral cavity), giant condyloma of Buschke and Löwenstein (anogenital area), and carcinoma cuniculatum (palmoplantar surface)
  • Females are at risk for progression to grade 2/3 cervical intraepithelial neoplasm (CIN) and, if left untreated, can eventually develop invasive cancer of the cervix.
  • Penile cancer, which is 10 times less common than cervical cancer, also has a high correlation rate with high-risk HPV infection and history of genital warts.

 

Warts on the prepuce

 

warts on the glans penis

 

Buschke–Löwenstein tumor or Giant condyloma acuminatum  is a rare cutaneous condition characterized by an aggressive, wart-like growth that is a verrucous carcinoma on the penis. The causative organism is Human Papilloma Virus (HPV). Due to their size, these tumors can be locally invasive and destructive, they destroy adjacent structures from compression. In general these masses are benign, but the potential for malignant transformation to squamous cell carcinoma (SCC) exists in the long term, as does the rare risk for metastasis. Buschke-Löwensteoin tumors are frequently associated with HPV subtypes 6 and 11.

Treatment involves surgical resection. Although penile sparing is the goal, total penectomy may be required. They have high recurrence rates.

 

Uretheral Warts

The human papilloma virus can also infect the urethera and form uretheral warts. They present a special problem for management since they can grow into the urethera or project out of the uretheral meatus (urinary opening). Fulgration of the warts in the urethera has risk of uretheral stricture and require cystoscopic / uretheroscopic fulgration. Long standing HPV infection of the urethera can cause uretheral cancers11, 12.

warts coming out of the uretheral meatus

 

Differntial diagnosis

DIFFERENTIAL DIAGNOSIS

Read more at Medical Dialogues: Genital Warts-Standard Treatment Guidelines http://speciality.medicaldialogues.in/genital-warts-standard-treatment-guidelines/
DIFFERENTIAL DIAGNOSIS

Read more at Medical Dialogues: Genital Warts-Standard Treatment Guidelines http://speciality.medicaldialogues.in/genital-warts-standard-treatment-guidelines/
  • Seborrhoeic keratoses
  • Lichen planus and nitidus
  • Molluscum contagiosum
  • Condyloma lata (syphilis)
  • Bowenoid papulosis
  • Pearly penile papules
  • Fordyce’s spots

(Pearly penile papules (PPP) are most common lesions confused with warts. The nodules are lined in symmetrical rows and are located most commonly on the corona of glans penis)

Pearly Penile Papules (PPP) are often confused with warts

 

PREVENTION AND COUNSELING

General measures as applicable to all patients with suspected Sexually Transmitted Infections

  • Blood Test for HIV, Syphilis and Hepatitis B.
  • Sexual abstinence during the course of treatment to minimize transmission. (or Avoid unprotected intercourse)
  • It is important to complete the treatment regimen (Specially for an ulcer/sore). No open ulcers / sore to be present on private parts.
  • Educate and counsel patient and sex partner(s) regarding (Reproductive tract infections) RTIs/ (Sexually transmitted infections) STIs, genital cancers, safer sex practices.
  • Both partners must be treated for the suspected organisms / Sexually transmitted diseases like chlamydia, syphilis, urinary tract infections, etc.
  • It is best to use barrier contraception like condoms.
  • Immunization against Hepatitis B and HPV.
  • Condoms can offer some protection from HPV infection, but HPV might be on skin that’s not covered by the condom. And condoms must be used every time, from start to finish. The virus can spread during direct skin-to-skin contact before the condom is put on, and male condoms don’t protect the entire genital area, especially for women. The female condom covers more of the vulva in women, but hasn’t been studied as carefully for its ability to protect against HPV. Condoms are very helpful, though, in protecting against other infections that can be spread through sexual activity.

    It’s usually not possible to know who has a mucosal HPV infection, and HPV is so common that even using these measures doesn’t guarantee that a person won’t get infected, but they can help lower the risk.

Key counseling messages to be conveyed to all patients diagnosed with HPV infection

  • Correct and consistent male condom use lowers the chances of giving or getting genital HPV, but it does not protect fully. There is always a risk of condom rupture or slipping of condom.
  • Treatments are available for the conditions caused by HPV but not for the virus itself.
  • enital HPV infection is very common and can also be spread by oral, anal and sexual contact.
  • It usually has no signs or symptoms until the warts manifest themselves.
  • The types of HPV causing genital warts (HPV type 6 &11 ) are different from the ones causing anogenital cancers (HPV types 16 & 18).
  • Warts do not affect a woman’s fertility or ability to carry a pregnancy to term, but is large can cause difficulty in Vaginal Delivery.
  • To lower the chances of getting infection, limit the number of partners.

HPV vaccines.

Two types which offer protection against the HPV types 16 and 18 that cause 70% of cervical cancers.

  • Gardasil: quadrivalent vaccine which also protects against the types 6 and 11. Three doses (0.5 ml IM at 0,2 and 6 months) Most effective when all three doses have been administered before any sexual contact.
  • Cervarix: bivalent vaccine against Type 16 and 18 (0.5 ml IM at 0,1 and 6 mths).

 

Low-risk human papillomavirus subtypes versus high-risk human papillomavirus subtypes

 

LOW RISK: HUMAN PAPILLOMAVIRUS

SUBTYPES 6 AND 11

HIGH RISK: HUMAN PAPILLOMAVIRUS

SUBTYPES 16 AND 18

Main pathologic association 75-90% cases of genital warts

70% cases of all invasive cervix cancer

 

Pathogenesis Remain separate from host cell DNA, undergo independent replication

Integrate viral DNA with host's genome promoting transcription of oncoproteins that inactivate tumor suppressor genes

Associated with which types of verrucous carcinoma

 

Oral florid papillomatosis Buschke-Lowenstein tumor

 

Oral florid papillomatosis
Vaccination HPV4 HPV2
HPV4

HPV 4: Gardasil (Merck & Co.), HPV2: Cervarix, (GlaxoSmithKline)

 

 

Gardasil (HPV9, Merck & Co.).

The recombinant, quadrivalent vaccine was intended for the prophylactic treatment of girls and young women 9 years though 26 years of age for the prevention of the following pathologies caused by HPV types 16 and 18: cervical, vulvar, and vaginal cancer, and condyloma acuminata. In addition, HPV4 is indicated for the prevention of precancerous or dysplastic lesions caused by HPV 6, 11, 16, and 18. Gardasil triggers the formation of host antibodies to the HPV subtypes, which are directly responsible for approximately 90 percent of genital warts and 70 percent of cervical cancers. Gardasil injections are administered in three separate doses and appear to be 99-percent effective in preventing genital wart formation in patients naïve to HPV infection.

 

Click here for more details about nonavalent HPV (Vaccine Gardasil -9)

Cervarix (HPV2, GlaxoSmithKline)

The vaccine for use in females ages 10 though 25 years. Cervarix is directed against two oncogenic types, HPV 16 and 18, which are associated with cervical cancer, cervical intraepithelial neoplasia grade 1 or worse, and adenocarcinoma in situ. The efficacy of HPV2 has been proven against HPV 16- or 18-related cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, which was 93 percent (95% CI 79.9–98.3). Comparable to the HPV4 safety data, injection-site pain, redness, and swelling were reported significantly more in the HPV2 group as compared to placebo. Fatigue, headache, and myalgia were the most common general symptoms. The dosing and administration schedules are similar to HPV4 where the second dose is administered 1 to 2 months after the baseline dose, and the third dose is administered six months after the baseline dose.

Overall, the American Cancer Society and Advisory Committee on Immunization Practices recommend routine vaccination of girls age 11 or 12 years with three doses of either HPV2 or HPV4. The vaccination series can be started beginning at the age of nine.

 

Latest being Gardasil - 9 vaccine which is active against 9 serotypes of HPV virus and there has been change in recommendation for vaccination for women and men.

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

This vaccine can prevent most cases of cervical cancer if given before a girl or woman is exposed to the virus. In addition, this vaccine can prevent vaginal and vulvar cancer in women, and can prevent genital warts and anal cancer in women and men.

In theory, vaccinating boys against the types of HPV associated with cervical cancer might also help protect girls from the virus by possibly decreasing transmission. Certain types of HPV have also been linked to cancers in the mouth and throat, so the HPV vaccine likely offers some protection against these cancers, too

Dosage -
If it is begun before age 15, boys and girls get two doses of HPV vaccine; the second vaccination should be given six to 12 months after the first dose.
 
If it's not given by then, the CDC recommends girls ages 15 to 26 and boys ages 15 to 21 receive three doses; the last two should be given one or two and then six months after the first.
 
Gay, bisexual and other men who have sex with men, transgender individuals and immunocompromised persons (including those with HIV infection) up to age 26 should also receive the vaccine regimen, according to CDC recommendations.
 

All HPV infections involve the transmission from one infected individual to another through direct skin-to skin-contact. This may occur through skin-to-skin transmission via the epidermis due to direct contact of a plantar wart virus with broken skin, sexually during intercourse, or orally during sexual activity or kissing. Symptomatic HPV infection is only the tip of the iceberg. Asymptomatic shedding is much more common in women with HIV/AIDS and asymptomatic shedders carry high potential for spreading the virus. Asymptomatic HPV/DNA shedding from perianal region seems to be very common.

There was no consistent evidence that condom use reduces the risk of becoming HPV DNA – positive (subclinical HPV infection). On the other hand, the risk for genital warts, CIN 2-3 and invasive cervical cancer were reduced by condom use.

 

Penile wart in the coronal sulcus of penis

 

Investigations for Human Papilloma virus (HPV)

  • COLPOSCOPY / Aceto-white test: Application of 3%–5% acetic acid, which causes HPV-infected genital mucosa to turn white in color on COLPOSCOPY in females.

  • LIQUID BASED CYTOLGY (LBC) - for detecting HPV infection in women
  • HPV DNA testing (PCR): Not recommended on a routine basis as test results would not alter clinical management of the condition.

  • BIOPSY - in suspicious lesions to rule out pre-cancerous lesions

 

Biopsy in Indicated in the lesions in the following conditions

  • the disease worsens during therapy
  • the warts are pigmented, indurated, fixed, bleeding, or ulcerated.
  • the diagnosis is uncertain
  • the patient has comprised immunity
  • the lesion is atypical
  • the lesions do not respond to standard therapy
  • The lesion shows a high risk of atypia

 

Screening for HPV virus

Screening for human papilloma virus is recommended only in women for vagina / cervix. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer (with high risk behaviour).

 

Screening in Women

PAP Test

A Pap test is used to find cell changes or abnormal cells in the cervix. Cells are lightly scraped or brushed off the cervix. The slides are stained with Papanicolaou stain and looked at under a microscope to see if the cells are normal or if changes can be seen. The Pap test is a gold standard test for screening of cervix for pre-cancerous cells or early cancer cell (CIN).

The American Cancer Society recommends that women between ages 21 and 29 should have a Pap test every 3 years (at ages 21, 24, and 27) to test for cervical cancer and pre-cancers, while it recommends that women aged 30 to 65 have an HPV test with their Pap test (co-testing) every 5 years to test for cervical cancer.The most common abnormal Pap test result seen is called ASC-US, these ASC-US cells usually are not pre-cancer, but they aren’t quite normal either. If there are ASC-US cells in your Pap test result, an HPV test may be done to see if HPV is causing the cell changes.

The recommendation for gap of 3 years / 5 years is recommended because cell changes in the cervix happen very slowly. It usually takes more than 10 years for cell changes to become cancer. Pap tests have been done every year (annually) in the past, but now it is known that Pap tests are not needed every year – every 3 years is enough.

 

Human Papilloma test (HPV) TEST in females

HPV is a virus that can cause cervix cell changes. The HPV test checks for the virus, not cell changes. The test can be done at the same time as the Pap test, with the same swab or a second swab. Pap test plus an HPV test (called co-testing) is the preferred way to find early cervical cancers or pre-cancers in women 30 and older.

Liquid based Cytology (LBC)

A newer technique for detecting Human Papilloma virus in females is liquid based cytology HPV testing. Liquid Based Cytology (LBC) is a new technique for collecting cytological samples in order to detect cervical cancer. With conventional cytology a smear taker takes a sample that is applied directly to a slide for microscopic investigation. With LBC, samples are collected in liquid vials and the slide is prepared semi-automatically at the laboratory. Potentially the advantages of LBC include a reduction in the number of inadequate slides and increased sensitivity of the test

The other tests that can be done to detect HPV lesions in females is Acetic acid test (Vineger) with colposcopy. It helps to detect flat lesions which cannot be detected by naked eye examination. 

Colposcopy and acetic acid test

Colposcopy is an outpatient procedure using a low-powered microscope, the colposcope. Colposcopy is the examination of the cervix, vagina, and in some instances the vulva after the application of acetic acid solution; coupled with obtaining colposcopically directed biopsies of all lesions suspected of representing neoplasia. Colposcopic findings are graded according to degree of acetowhite lesion, surface contour, mosaic pattern, and punctuation. Greater abnormalities of these parameters are related to severity of the lesions.

Acetic acid test

  • Soaking acetic acid into suspicious lesions can enhance the degree of suspicion in lesions without classic features.

  • The method involves applying a 3–5% acetic acid–moistened gauze pad for 5-10 minutes on suspected lesions of the penis, cervix, labia, or perianal area.

  • Inconspicuous, flat, genital lesions that might be difficult to assess become visible. Genital warts, dysplastic, and neoplastic tissues turn white (acetowhite).

  • False-positive results are common and can result from anything that causes parakeratosis (e.g., candidiasis, psoriasis, lichen planus, healing epithelium, sebaceous glands).

  • The acetic acid test should not be used for routine screening.

  • It can be used for visualizing subclinical genital HPV-associated lesions, identifying lesions for target biopsy, and for demarcating lesions during surgical therapy.

 

 

What does HPV postive test mean

Cervical HPV infection and a normal Pap test result - it means that there is genital human papilloma virus (HPV) presence, but no cell changes were seen in the Pap test. There are 2 options:

Repeat test for HPV and Pap test again in 12 months.

In most cases, re-testing in 12 months shows no sign of the virus, as body immunity would have taken care of the virus. or If the virus does go away and Pap test is normal, then normal screening with PAP test and HPV should be done as recommended every three years from 25  to 49 years of age and every 5 years above 50 years of age.

If the virus is still there or changes are seen on the Pap test, you’ll need more testing. As another option, testing specifically for HPV-16 or both -16 and -18 (the 2 types that are most likely to cause cervical cancer) is done.

If testing shows that you have HPV-16 and/or -18, more testing will be needed  for precancerous cells.

If the test doesn’t show infection with HPV-16 and/or -18, then repeat testing in 12 months with both an HPV test and a Pap test.

Screening in men

Despite the morbidity associated with anogenital condylomas and the mortality associated with anal, penile, and cervical carcinoma as a direct consequence of human papillomavirus (HPV), the routine screening for HPV in immuno competent men is not recommended. However, the high-risk populations of men who have sex with men and men who test positive for human immunodeficiency virus (HIV), in whom HPV infection is pervasive and persistent, may benefit from screening. Therefore, HPV screening, including anal cytology, should be considered for these men in settings where appropriate follow-up, including high-resolution anoscopy, is available. But still there is no recommendation for Human Papilloma virus (HPV) test for men at this time, nor is there any approved HPV test to find the virus anywhere besides the cervix, including the mouth or throat.

The HPV sample collection which yields the most diagnostic sensitivity involves running an emery board across the skin at multiple sites followed by a wet Dacron swab to collect cells. Although 3 HPV DNA testing kits are commercially available for use in women (Hybrid Capture II, Cervista HPV HR and Cervista HPV 16/18), none for use in men. Therefore in men we can use the same kits for screening for HPV.

Finally there is also an argument given that , there’s no useful / advantage to test for a person’s “HPV status,” because an HPV test result can change over a period of months or years as the body fights the virus and body immunity destroys the lesions. 

 

Penile HPV Screening

Penile screening for HPV is not recommended because of the high prevalence of penile human papilloma virus (HPV) and the generally self-limited duration of infection in immuno-competent men. Little data is available regarding the natural history of HPV infection and the development of PIN (penile cancer in situ) or invasive penile cancer in (men having sex with men) MSM or HIV-positive men.  PIN (penile cancer in situ) cannot be diagnosed by cytology; any suspicious penile lesion requires biopsy for pathology. 

 

This is how the tests for the HPV sequencing and typing is reported as given in the report below.

 

This is a report from lab. showing the detection of the HPV virus and the serotyping done showing type 11 serotype.

 

Click here for The HPV and Men - fact sheet published by CDC (Communicable and Disease control Atlanta America)

 

Treatment

  • No single treatment is ideal for all patients or all warts.
  • No definitive evidence that any of the available treatments are superior to any other.
  • Spontaneous resolution of lesions may also occur.

 

Recommended regimens:

NATIONAL AIDS CONTROL ORGANISATION 's (NACO's) :

National Guidelines on prevention, management and control of Reproductive tract infections including sexually transmitted Infections  - Click here to Download PDF file

 

Treatment of Genital warts - Penile, scrotum, vulval, vaginal  and perineum

 

  • Imiquimod 5% cream or 12.5mg cream (Recommendation -Grade A)  (Imiquimod 5% or 12.5 mg cream is same as 5% imiquimod is 5mg in 100 mg cream base, that means 10 mg in 200 mg cream base or 12.5 mg in 250 mg cream base) - is a patient-applied topical immunomodulatory agent, applied at bedtime 3 times weekly for up to 16 weeks; the treatment area should be washed with soap and water 6-10 hours after the application. Imiquimod cream should be applied 3 times per week (example: Monday, Wednesday, and Friday; or Tuesday, Thursday, and Saturday) prior to normal sleeping hours, and should remain on the skin for 6 to 10 hours. Imiquimod cream treatment should continue until the clearance of visible genital or perianal warts or for a maximum of 16 weeks per episode of warts. If a dose is missed, the patient should apply the cream as soon as he/she remember and then he/she should continue with the regular schedule. However the cream should not be applied more than once a day. Imiquimod cream should be applied in a thin layer and rubbed on the clean wart area until the cream vanishes. Only apply to affected areas and avoid any application on internal surfaces. Imiquimod cream should be applied prior to normal sleeping hours. During the 6 to 10 hour treatment period, showering or bathing should be avoided. After this period it is essential that imiquimod cream is removed with mild soap and water. Application of an excess of cream or prolonged contact with the skin may result in a severe application site reaction. A single-use sachet is sufficient to cover a wart area of 20 cm2 (approx. 3 inches2). Sachets should not be re-used once opened. Hands should be washed carefully before and after application of cream. Imiquimod cream therapy is not recommended until the skin has healed after any previous drug or surgical treatment. Application to broken skin could result in increased systemic absorption of imiquimod leading to a greater risk of adverse events. The use of an occlusive dressing is not recommended with imiquimod cream therapy. Imiquimod is a synthetic agent with immune response modifying activity. Imiquimod 5% cream has been used in the treatment of a variety of skin conditions, including basal cell carcinomas and actinic keratoses. Although its precise mechanism of action remains unclear, imiquimod is believed to activate immune cells by binding to the membranous toll-like receptor. This leads to the secretion of multiple cytokines, such as interferon-α, interleukin-6, and tumor necrosis factor-α, which are critical in the induction of an inflammatory response promoting wart clearance. Imiquimod cream should be used with caution in patients with autoimmune conditions. and inflammatory conditoins. In addition, imiquimod-treated patients have been shown to have a decrease in viral load measured by HPV DNA, a decrease in messenger ribonucleic acid (mRNA) expression for markers of keratinocyte proliferation, and an increase in mRNA expression for markers of tumor suppression. As an immune response modifier (IRM), imiquimod stimulates cytokine production, especially interferon production. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. For the treatment of Condylomata Acuminata, imiquimod is applied at bedtime three times per week for up to 16 weeks. Commonly encountered local inflammatory side effects, such as itching, erythema, burning, irritation, tenderness, ulceration, and pain, have been long-standing issues with the 5% cream. Occasionally, patients may experience systemic side effects of headaches, muscle aches, fatigue, and general malaise. Wart clearance was achieved in 56 percent of patients. with a low recurrence rate (13%). Rarely, intense local inflammatory reactions including skin weeping or erosion can occur after only a few applications of imiquimod cream. Local inflammatory reactions may be accompanied, or even preceded, by flu-like systemic signs and symptoms including malaise, pyrexia, nausea, myalgias and rigors, the application of the cream should be stopped immediately.
    Click here to know more about Imiquad (Imiquimod Cream) 5% cream or (12.5mg in 0.25gm cream sachet)

 

  • Podophyllotoxin 0.05% solution or gel and 0.15% cream (Recommendation - Grade A).

    Podophyllotoxin is a purified extract of the podophyllum plant, it is a non-alkaloid toxin lignan extracted from roots and the rhizomes of podophyllum species. The toxin binds to cellular microtubules, inhibits mitotic division, and induces necrosis of warts that is within 3 to 5 days after administration. The solution is applied with a cotton swab or with a finger to genital warts twice a day for 3 days, followed by 4 days of no therapy; repeated as needed for up to 4 cycles (total wart area treated should not exceed 10 cm2, and total volume of medicaton should be limited to 0.5 mL/day). Shallow erosions occur as the lesions necrotize and heal within a few days.

    This treatment option is generally thought to be safe, effective, and can be self-administered. Podophyllotoxin is available as a solution, cream, or gel and must be applied twice daily for three consecutive days of the week, for a maximum of four weeks. Typically, the solution is recommended for penile lesions, whereas cream or gel vehicle preparations are thought to be more comfortable for application to anal or vaginal lesions. various studies have shown successful clearance rates ranging between 45 to 77 percent.  Podophyllotoxin is also associated with rates of recurrence as low as 38 percent. Warts that have not resolved after four courses should be treated by alternative means. Adverse effects tend to be fairly common, especially with the first course of therapy and include pain, inflammation, erosion, burning, or itching at the application site. Severe systemic effects of peripheral neuropathy, coma, and hypokalaemia can follow application of large quantities. During pregnancy, it is best to offer no treatment. Podophyllin is contraindicated in view of its toxicity and possible mutagenic action, and the warts usually diminish in size once pregnancy has ended. Trichloracetic acid may be used if the lesions are discrete and small and occur on the vaginal wall or vulva.

 

  • Sinecatechins 15% ointment (Recommendation - Grade A).

    Sinecatechins is a botanical extract for the treatment of genital warts, making it the first botanical extract to officially receive medical approval. The active ingredient is a green tea extract containing sinecatechins, which is thought to possess antioxidant, antiviral, and antitumor effects. Although the precise mechanism of action remains unclear, sinecatechins is thought to modulate the inflammatory response through the inhibition of transcription factors AP-1 and NF-κB, both of which are induced by reactive oxygen species. They have also been shown to downregulate the expression of cyclooxygenase-2, which has been linked to activation of the prostaglandin E2 system and subsequent epithelial dysplasia.

    Sinecatechins 15% cream is applied topically to warts three times a day for up to four months. Typically, if an improvement is not seen within a few weeks, the treatment is stopped and another option is tried. Several randomized, double-blind, placebo-controlled trials have shown sinecatechins to be significantly more effective than placebo in the treatment of genital warts, with clearance rates as high as 58 percent. Recurrence rates are also relatively low, ranging between 6 to 9 percent at 12 weeks follow up.

    This botanical extract is associated with a number of adverse effects that are thought to occur in approximately 20 percent of users. These events are generally quite mild and typically include redness, burning, itching, and pain at the site of application. More severe reactions associated with this topical product’s use, such as lymphadenitis, vulvovaginitis, balanitis, and ulceration are extremely rare, but have been reported.

 

  • Trichloroacetic acid (TCA) 80–90% solution (Grade B) 

    80 - 90 %, to be every once every two weeks. TCA is a chemically destructive acid that burns, cauterizes, and erodes the skin and mucosa. Generally prepared in 80 to 90% solutions, TCA necessitates administration by the physician. Successful treatment of warts can occasionally occur with as little as a single dose; however, more frequently, several applications are required.

    TCA is an inexpensive, cost-effective treatment that does require prolonged usage and regimen adherence. The destructive nature of the product frequently extends beyond the superficial wart to encompass the underlying viral infection providing for clearance rates that have been estimated at 70 to 80 percent with high recurrence rates of 36 percent.

    Additionally, the low danger of systemic absorption allows for safe application during pregnancy. The main side effects of acid treatments involve pain or burning during administration as well as destruction of the healthy tissue surrounding the wart. The latter can be minimized by washings with soap and sodium bicarbonate immediately following over-application, and dermal injury or scarring is rare. Occasionally, tissue destruction can result in pain, ulceration, and crust formation. High success rates and relatively low morbidity make acetic acid therapy a recommended treatment option for Condylomata Acuminata.Cryotherapy (Recommendation - Grade B).

 

  • Cryotherapy

    Cryotherapy is a process in which the abnormal tissue is frozen through the use of a cooling agent, such as nitrous oxide or liquid nitrogen. Temperatures must be exorbitantly cold so as to cause permanent dermal and vascular damage. This leads to the initiation of an immune repair response, resulting in the necrosis and clearance of the destroyed cells. Generally, this treatment is most effective when used for multiple small warts on the penile shaft or vulva.

    Cryotherapy is considered a fairly inexpensive and highly successful therapy, with a 79- to 88-percent clearance rate seen within the first three treatments. This suggests a more efficacious outcome when compared with Trichoroacetic acid (TCA). Cryotherapy has various limiting factors. Variables in administration, such as the temperature utilized and time of contact, influence efficacy of treatment. Common side effects of cryotherapy include local tissue destruction, such as painful blistering, ulceration, infection, potentially permanent scarring, and loss of pigmentation, which can be slightly more severe than that of TCA therapy.

    Additionally, as with other lesion-directed therapies, cryosurgery does not treat subclinical lesions in the surrounding skin. The recurrence rate associated has been estimated to be between 25 and 40 percent. Other disadvantages of cryotherapy are that multiple outpatient visits are required and the pain associated with its application can limit its repeated use in certain subjects. However, the effects of cryotherapy are entirely local, making it the current therapy of choice for pregnant women with multiple warts.

 

  • Electrosurgery (Recommendation - Grade B). - 

    Electrosurgery involves the use of high frequency electrical currents in the form of thermal coagulation or electrocautery to burn and destroy warty lesions. The desiccated tissue is subsequently removed by curettage. This technique is particularly efficacious when used in the treatment of smaller warts located on the shaft of the penis, the rectum, or the vulva; however, it is not recommended for large lesions as it may lead to permanent scar formation. Electrosurgery is an extremely effective technique, with randomized, controlled trials yielding clearance rates as high as 94 percent measured six weeks post-treatment. These rates, however, tend to normalize after three months, suggesting that electrosurgery is comparable to cryotherapy with regard to its long-term effectiveness. Electrosurgery is also a fairly painful procedure and local or general anesthesia is usually required. Side effects tend to be relatively minimal and are typically limited to post-procedural pain. Electrosurgery followed by imiquad is the treatment of choice for the ano-genital warts10.

 

 

 

Electro-coagulation / Electro-fulgration of warts

Click here to watch this video on youtube

 

  • Surgical excision (Recommendation - Grade B).

    One of the oldest documented treatments for the removal of genital warts, surgical excision was considered for many years to be the primary available option. It involves the physical removal of diseased tissue from the body with scissors or a scalpel, followed by suturing the remaining healthy skin together. It is associated with up to a 72-percent clearance rate, which is evident immediately and often persisting over a year later. This treatment option is suitable for very large lesions that may be causing obstruction and are ineligible or unresponsive to other forms of treatment. Examples include lesions involving the urethral meatus.

    Additionally, surgical excision remains the optimal procedure for the removal of neoplastic lesions suspected of malignant progression, which must be submitted for further histopathological examination. Surgical removal of large lesions is a painful process, which frequently results in bleeding and scar formation. The administration of local or general anesthesia is commonly recommended.

 

  • Laser ablation therapy (Recommendation - Grade B).

    Laser is light amplification by stimulated emission of radiation. Laser is a concentrated energy beam which is focused on the tissue causing it to evaporate. Commonly used laser energy sources are Carbon dioxide laser Argon Laser, Nd-YAG laser, diode laser etc. The intense light energy has the added benefit of providing immediate cauterization of any ligated vessels, ensuring a virtually bloodless procedure. The spatial confinement of the laser beam permits precise tissue ablation resulting in rapid healing with little or no scar formation.

    The efficacy of Laser therapy for Condylomata Acuminata remains debatable. Laser therapy is typically considered to be less effective than other forms of surgical treatment, with clearance rates ranging between 23 to 52 percent. Recurrence rates also tend to be elevated, reaching as high as 77 percent. Side effects are generally mild and limited to the burning of tissue surrounding the lesion. Despite these seemingly unfavorable results, the deep penetrating effect of the laser often allows for a greater and more complete viral attack than seen with other surgical treatment options. This renders it the treatment of choice for immunosuppressed individuals as well as for pregnant women with extensive lesions who remain unresponsive to TCA or cryotherapy.

    Unfortunately, laser therapy is also a rather expensive and complicated treatment option. Furthermore, vaporization of viral lesions can lead to the release of HPV DNA into the surrounding environment. Appropriate measures must therefore be undertaken in order to ensure physicians and assisting personnel are protected from infection. This necessitates the use of specific, virus-resistant masks as well as a vacuum ventilation system in the examination room. Additional risk factors for the transmission of genital warts through vaporization include treatment of malignant HPV subtypes, thinness of skin, and the degree of viral burden.

 

Genital warts may go away on their own. Also, treating genital warts may not cure a human papillomavirus (HPV) infection. The virus may remain in the body in an inactive state after warts are removed. A person treated for genital warts may still be able to spread the infection. Condoms may help reduce the risk of HPV infection.

 

Other Misc Therapies

  • Intra-lesional Vitamin D injections - Intralesional vitamin D injections

    Vitamin D has been discovered to show a modulatory and regulatory role in multiple processes involving immunity, host defense, inflammation and epithelial repair, in addition to its essential functions in the regulation of calcium homeostasis. Although the exact mechanism of vitamin D activity against warts has not been identified, the effect of vitamin D was speculated to be derived from its immune-regulatory activities, its potential role in regulation of epidermal cell proliferation and differentiation and its modulation of cytokine production. The wart to be injected was cleaned by alcohol and then injected with 0.1 mL of prilocaine (20 mg/mL). 0.2 mL of vitamin D3 (7.5 mg/mL) solution was slowly injected into the base of each wart. The maximum total amount of vitamin D3 injected into a patient in one session was 7.5 mg. The injection was done at 4 weeks interval until clearance or for a maximum of two sessions.

 

  • THUJA - Tincture of Thuja in ointment (local application) / oral drops (systemic administration) in the treatment of warts

    extract from Thuja occidentalis (White cedar tree) - T. occidentalis, an extract from white cedar (Arbor vitae or the white oak) is indigenous to eastern North America and grown in Europe as an ornamental tree. The leaves & twigs on steam distillation yield 0.6 to 1.0% camphor like essential oil called oil of thuja or white cedar leaf oil, sp.gr. 0.925, boiling point 190-206c, easily soluble in alcohol. The main constituent of the oil is d-thujone which is poisonous (W.I., 1976). It acts on the muscles of the uterus, Americans drink a tea of the inner bark to promote menstruation. Thuja also contain volatile oil, sugar, gelatinous matter, wax, resin and thujin. Volatitle oil can be distilled from leaves and used as vermifuge In folk medicine, extract from dried twig tips has been used to treat bronchial catarrh, enuresis, cystitis, psoriasis, uterine carcinomas, amenorrhea, and rheumatism. The drug contains 1.4-4% essential oil (critical factor as medicinal herb), 60% of which is thujone, which corresponds to 2.4% thujone in the whole drug. The pharmacological potential of T. occidentalis has been investigated in various in vitro and in vivo studies. It showed significant increase in interleukin 1, interleukin 6, and tumour necrosis factor alpha and caused local activation of cytokine producing cells for priming without a systemic rise. THUJA causes T-cell induction particularly of Cluster Differentiation 4 (CD 4) positive T-helper cells in connection with an increased production of Interleukin. Thus, thuja has shown definite anti-human immunodeficiency virus-1 activity. A 2-year prospective clinical and therapeutic experience of patients with HPV infection diagnosed based on cytology and or biopsy, which had recurred after treatment found that thuja helped to eradicate the papillomatous lesions. While some studies showed Thuja - 200 systemic theraphy having no effect on warts.

 

Therapies not generally recommended.

Due to low efficacy and toxicity, routine use of podophyllin, 5-fluorouracil (5-FU), and interferon therapy are not recommended for use in the primary care setting.

  • Podophyllin

    was the first topical treatment of genital warts; however, a lack of standardized drug preparation lead to samples that varied greatly in the active ingredient. This increased the likelihood for adverse skin reactions, such as burning, redness, pain, itching, or swelling. In extremely rare circumstances, over-application of podophyllin and excessive systemic absorption has been linked to the development of enteritis, bone-marrow suppression, abdominal pain, and neurological compromise. Podophyllin fails to induce a lasting remission of genital warts and is generally considered less effective than podophyllotoxin, cryotherapy, or electrosurgery when used as individual modalities.

 

  • 5 - Fluorouracil (5-FU) - 

    is one of the oldest chemotherapeutic agents and has been effectively used in the treatment of cancer for more than 40 years. Although not officially approved for use in the treatment of genital warts, topical 5-FU is still seen as a favorable option for urethral warts. The administration of 5-FU has historically been associated with highly variable response rates, and side effects tend to be slightly more severe than those of imiquimod 5% cream with comparable clearance rates yet marginally higher rates of recurrence.

 

  • Interferon therapy -

    has been used predominantly for the treatment of malignant melanoma; however, recent evidence suggests that it may be useful as either an individual or adjuvant to surgical treatment of genital warts. Interferon therapy can be administered systemically, via oral or intramuscular injection, as well as locally, via direct intralesional injections. Typically, 1 to 1.5 million units is used, and injections over three times a week for a duration of three weeks. The use of interferon therapy for the treatment of genital warts remains somewhat controversial. The rate of complete response of systemically used interferon and placebo had no perceivable difference. Due to its direct immune-boosting effects, interferon therapy is likely to promote the clearance of underlying virally infected cells in addition to targeting external lesions. This may ultimately lead to lower rates of recurrence and better long-term results, especially when used synergistically with other treatment modalities. The benefit of interferon therapy as an adjunct treatment remains unclear, with several studies indicating no advantage relative to placebo, while still others show a significant improvement in treatment results. Although this therapy seems promising, further comprehensive research is needed in order to confidently evaluate its effectiveness. Side effects generally include flu-like symptoms, such as headache, nausea, vomiting, fatigue, and myalgia. On rare occasions, systemic interferon therapy has been linked to elevated liver enzymes, bone marrow suppression, bronchospasms, and depression. Intralesional injections are associated with significant pain upon administration, hence the use of local anesthesia is frequently recommended. The use of interferon therapy is an extremely costly procedure and is typically considered the most expensive genital wart treatment. Given the ongoing controversy surrounding the effectiveness of this treatment, interferon therapy is generally considered a last-resort therapy reserved for severe cases that are unresponsive to other forms of treatment.

     

    Generic Name Brand Name
    interferon alfa-2b Intron A
    interferon alfa-n3 Alferon N
    interferon beta-1b Betaseron
    interferon gamma-1b Actimmune

     

    Interferon can kill viruses and prevent them from reproducing. It also stimulates the body's immune system to fight viruses.

    Interferon is given by injection just under the skin at the base of the wart. A common injection schedule is 3 injections a week for 3 weeks or

    2 injections a week for 8 weeks, depending on the type of interferon.

     

    Side Effects of Interferons

    Interferon injected into warts has side effects such as:

    • Fever and chills.
    • Muscle aches.
    • Pain at the injection site.
    • Utricaria
    • A temporary decrease in white blood cells, which fight infection in the body.
    • A decrease in the blood platelets (Thrombocytopenia)
    • Flu-Like Syndrome - Flu-like syndrome occurs in a majority of patients because of the "revving-up" of the immune system. It generally occurs within hours of the injection and includes fever, chills, headache, muscle and joint aches, and poor appetite.
    • Fatigue
    • Low White Blood Cell Count (Leukopenia or Neutropenia)
    • Headache
    • Nausea and/or Vomiting
    • Diarrhea
    • Mood Disturbances - Interferon alfa has been reported to cause mood disturbances, depression, anxiety, aggressive behavior, suicidal thoughts, and even suicide.
    • Low Red Blood Cell Count (Anemia)
    • Loss or Thinning of Scalp and Body Hair (Alopecia)

    Less common, but important side effects of Interferons can include:

    • Liver Toxicity
    • Allergic Reaction
    • Thyroid Problems
    • Lung Changes
    • Heart Problems
    • Rash 
    • Vision Changes - While receiving interferon alfa, some patients may develop vision or eye problems like eye pain, swelling, redness or any vision changes, including blurriness, double vision and sensitivity to light.
    • Stroke
    • Elevated Cholesterol Level
    • Sexual & Reproductive Concerns - This medication may affect your reproductive system, resulting in the menstrual cycle becoming irregular or stopping permanently. Women may experience menopausal effects including hot flashes and vaginal dryness. In addition, the desire for sex may decrease during treatment

       

     

 

 Organ Specific Wart Treatments

Cervical warts

  • The treatment modality should be changed if a patient has not improved substantially after a complete course
  • Cryo cauterization is the treatment of choice.
  • Podophyllin is contraindicated.
  • Biopsy of warts to rule out malignant change.
  • Cervical cytology should be periodically done in the sexual partner(s) of men with genital warts.
  • Electro-cautery
  • TCA

 

Vaginal Warts

  • Cryo-cuaterisation
  • TCA (Tri chloro acetic acid) 80%–90% applied to warts.
  • Electro-cautery

 

Urethral Meatus Warts

  • Podophyllin 10%–25% in compound tincture of benzoin.
  • Cryotherapy with liquid nitrogen
  • Imiquimod use
  • Electro-cautery

 

Anal Warts

  • TCA (Tri chloro acetic acid) 80%–90% applied to warts.
  • Cryotherapy with liquid nitrogen
  • Surgical removal
  • Electro-cautery
  • Immuno-modulation

 

 

Alternative Regimens

  • photodynamic therapy
  • intralesional interferon
  • topical cidofovir.

 

Special Considerations

Pregnancy

  • HPV types 6 and 11 can rarely cause respiratory papillomatosis in infants and children. Whether cesarean
  • pelvic outlet is obstructed
  • pregnancy is complete.
  • genital warts can proliferate and become friable
  • Imiquimod, podophyllin not to be used
  • Removal of warts during pregnancy can be considered, though resolution might be incomplete or poor until
  • Cesarean delivery for women with genital warts is indicated if
  • Vaginal delivery would result in excessive bleeding.
  • section can prevent this is unclear, hence this is not an absolute indication for caesarean delivery.

HIV Infection

  • Lesions are more recalcitrant to treatment
  • more likely to develop genital warts
  • Same treatment regimes to be followed, however, might not respond as well and might have more frequent recurrences after treatment
  • Squamous cell carcinomas arising in or resembling genital warts are more frequent, hence biopsy for confirmation of diagnosis in suspicious cases.
  • Screening for anal intraepithelial neoplasia by cytology recommended in HIV-infected MSM (men having sex with men)within the anogenital tract.

 

 

 Summarizing in Table format

Treatment Modalities for Genital Warts

TOPICAL

TREATMENT TYPE -

TOPICAL

MECHANISM OF ACTION ADMINISTERED BY LEVEL OF EVIDENCE CLEARANCE % RECURRENCE % COMMENTS
             
Podophyllotoxin Anti-wart lignans Patient A 45-77 % 38-65 % Home treatment
             
Imiquimod 5% cream

Induces secretion of cytokines that reduce HPV DNA viral load

Patient A 56 % 13% Lengthy duration and sporadic dosing frequency can affect compliance
             
Sinecatechins 15% ointment Possess antitumor, antiviral, antioxidant effects Patient A 58 % 6-9% Can often take 16 weeks to elicit positive response
             
5-FU Inhibits key enzyme in DNA replication Physician or Surgeon C 10 - 50% 50% Sometimes used for urethral warts
             

 

 

 

Treatment Modalities for Genital Warts

Ablative / Surgical

TREATMENT TYPE -

TOPICAL

MECHANISM OF ACTION ADMINISTERED BY LEVEL OF EVIDENCE CLEARANCE % RECURRENCE % COMMENTS
             
Tri-chloro acetic acid (TCA)  Chemically destructive acids  Surgeon B 70 %  18 % High clearance rates with relatively low morbidity
             
Cryotherapy Dermal damage induced by cold temps initiate immune response Surgeon B 79 - 88 %  25 - 40 % Treated areas can take several weeks to heal, requires multiple treatments
             
Electrosurgery

Thermal coagulation

Surgeon B 94 %  22 %

Most Effective treatment but requires local anaesthesia10

             
Surgical excision  Physical removal of diseased tissue  Surgeon B 72 %  19-29 %  For Large Lesions
             
Laser Ablation  light energy vaporizes lesions  Surgeon B 23 - 52 %  60-77 %  very costly as compared to other treatment modalities without much benefit
             
 Systemic Therapy            
             
Interferon Thearpy Interferes with viral replication Physcian C 17 - 67 % 9 - 69 % Systemic use has comparable clearance rates versus placebo Very costly treatment
             

 

 Summarizing

Current treatment options focus predominantly on removal of the external wart rather than attacking the underlying viral infection and have thus proven somewhat inadequate in achieving effective long-term results. Therapies can be categorized as topical, surgical, or immunomodulatory and can differ quite significantly in terms of cost, duration of therapy, dosing schedules, and adverse effects. As of yet, there is little evidence to suggest that one class of treatments is not more effective than another nor has a single therapy emerged as the gold standard for treatment. Selection of a therapeutic modality typically depends on the needs and desires of the individual patient.

Given the strikingly high prevalence of genital warts among the population, and the lack of adequate therapies, HPV vaccines such as HPV4 and HPV2 may play a significant role in reducing the burden of disease by preventing viral infection and transmission. Studies evaluating the effectiveness of HPV vaccines in preventing genital wart infection have shown it to be both safe and extremely successful in both sexes.

 

 

 

References

  1. Yanofsky VR, Patel RV, Goldenberg G. Genital warts: a comprehensive review. J Clin Aesthet Dermatol. 2012;5(6):25–36. 
  2. Naglaa N. El Mongya, Rana F. Hilala, Amul M. Badrb and Samah A. Alraawi. Serum vitamin D level in patients with viral warts. Journal of the Egyptian Women's Dermatologic Society: September 2018 - Volume 15 - Issue 3 - p 133-138.
  3. Kavya M, Shashikumar BM, Harish MR, Shweta BP. Safety and Efficacy of Intralesional Vitamin D3 in Cutaneous Warts: An Open Uncontrolled Trial. J Cutan Aesthet Surg. 2017;10(2):90–94. doi:10.4103/JCAS.JCAS_82_16.
  4. Joseph R, Pulimood SA, Abraham P, John GT. Successful treatment of verruca vulgaris with Thuja occidentalis in a renal allograft recipient. Indian J Nephrol. 2013 Sep;23(5):362-4. doi: 10.4103/0971-4065.116316. PubMed PMID: 24049274; PubMed Central PMCID: PMC3764712.
  5. Rajatrashmi, Sarkar M, Vikramaditya. Pharmacognostic Studies of Thuja Occidentalis Linn. - A Good remedy for warts & tumours, used in Homeopathy. Anc Sci Life. 1999;19(1-2):52–58.
  6. Sait MA, Garg BR. Treatment of Wam- A Study of One Hundred and Six Cases. Indian J Dermatol Venereol Leprol. 1985 Mar-Apr;51(2):96-98. PubMed PMID: 28164948.
  7. McGinley KF, Hey W, Sussman DO, Brown GA. Human Papillomavirus Testing in Men. J Am Osteopath Assoc 2011;111(3_suppl_2):S26–S28.
  8. Dixit R, Bhavsar C, Marfatia YS. Laboratory diagnosis of human papillomavirus virus infection in female genital tract. Indian J Sex Transm Dis AIDS. 2011;32(1):50–52. doi:10.4103/0253-7184.81257
  9. Burd EM. Human Papillomavirus Laboratory Testing: the Changing Paradigm. Clin Microbiol Rev. 2016;29(2):291–319. doi:10.1128/CMR.00013-15.
  10. Bertolotti A, Milpied B, Fouéré S, Dupin N, Cabié A, Derancourt C. Local Management of Anogenital Warts in Non-immunocompromised Adults: A Systematic Review and Meta-analyses of Randomized Controlled Trials. Dermatol Ther (Heidelb). 2019 Dec;9(4):761-774. doi: 10.1007/s13555-019-00328-z. Epub 2019 Oct 13. PMID: 31606873; PMCID: PMC6828858.
  11. Zhang M, Adeniran AJ, Vikram R, Tamboli P, Pettaway C, Bondaruk J, Liu J, Baggerly K, Czerniak B. Carcinoma of the urethra. Hum Pathol. 2018 Feb;72:35-44. doi: 10.1016/j.humpath.2017.08.006. Epub 2017 Aug 18. PMID: 28827100; PMCID: PMC5975388.
  12. Iorga L, Dragos Marcu R, Cristina Diaconu C, Maria Alexandra Stanescu A, Pantea Stoian A, Liviu Dorel Mischianu D, Surcel M, Bungau S, Constantin T, Boda D, Fekete L, Gabriel Bratu O. Penile carcinoma and HPV infection (Review). Exp Ther Med. 2020 Jul;20(1):91-96. doi: 10.3892/etm.2019.8181. Epub 2019 Nov 11. PMID: 32518604; PMCID: PMC7273896.

Read more at Medical Dialogues: Genital Warts-Standard Treatment Guidelines http://speciality.medicaldialogues.in/genital-warts-standard-treatment-guidelines/
within the anogenital tract.

Read more at Medical Dialogues: Genital Warts-Standard Treatment Guidelines http://speciality.medicaldialogues.in/genital-warts-standard-treatment-guidelines/
within the anogenital tract. Ministry of Health and Family Welfare, Government of India has issued the Standard Treatment Guidelines for Genital Warts. Following are the major recommendations :

Read more at Medical Dialogues: Genital Warts-Standard Treatment Guidelines http://speciality.medicaldialogues.in/genital-warts-standard-treatment-guidelines/
within the anogenital tract. Ministry of Health and Family Welfare, Government of India has issued the Standard Treatment Guidelines for Genital Warts. Following are the major recommendations :

Read more at Medical Dialogues: Genital Warts-Standard Treatment Guidelines http://speciality.medicaldialogues.in/genital-warts-standard-treatment-guidelines/

Anal and Peri-Anal Warts

 

What are Anal Warts?

Anal warts (condylomas) are small skin-colored or pink-colored growths or spots in or around the anus. These growths can become large and cover the entire anal area.
 
“ The word “condyloma” comes from the Greek word meaning “knob.” Any knob-like or warty growth on the genitals is known as a condyloma. The warts in HPV infection are called as condyloma acuminata or codyloma Acuminatum (while warts like growth in secondary syphilis is called as condyloma lata which can be confused with presentation of condyloma acuminata8).

Anal warts are one of the most common sexually transmitted infections in world. They are caused by a small DNA virus, a papillomavirus belonging to the papovavirus group, which cannot be cultured. Genital warts differ from skin warts histologically and antigenically. Genital warts are nearly always
transmitted by sexual contact; autoinoculation from hand to genitals is unusual. The infectivity of sexually acquired warts is about 60%; the incubation period is long, varying from two weeks to eight months.

Four distinct sub-types of Ano-genital warts have been described: condylomata acuminata (pointed warts), flat / macular lesions, papular, and keratotic lesions. The first two sub-types are mainly found on moist, non-keratinized epithelia, while the latter two usually present on keratinized epidermis. Ano-genital warts are also often referred to as genital warts, condylomata acuminata or genital verruca.

Anal/ peri-anal/ Ano-genital warts are highly infectious; approximately 65% of individuals with an infected partner develop the lesions within 3 weeks and 8 months after exposure, the median time between infection with HPV types 6 or 11 and the development of warts was 11 to 12 months among males and 5 to 6 months among young females. In rare cases, Ano-genital warts can be associated with malignant lesions, namely Buschke-Lowenstein tumors.

 

 

 Multiple Peri-anal warts (Condyloma acuminata)

 

Multiple Peri-anal warts (Condyloma acuminata)

 

 

Diagrammatic representation of Anal Warts is shown below

 

Diagram showing warts in the Anal canal and peri-anal skin (Also Anal verge)

 

 

Peri-anal and Anal Warts (Diagramatic) 

 

 

Peri-anal and Anal Warts (Diagramatic)

 

 

 

Symptoms of Anal Warts

Anal warts are a commonly transmitted sexual infection among young adults. It is a painless condition and most are unaware as there are no symptoms. There is a common complain of anal itching. Tiny spots or growths can be seen and also can be felt with fingers. When they become large, one may feel a lump or mass in the anal area. The other symptoms noticed in anal or peri-anal warts are bleeding or increased mucus discharge. pain, itching, burning, irritation, 

The infection with Human papilloma virus (HPV) can cause emotional and psychological problems with the person which includes shame, embarrassment, anger, depression and guilt. Since the Anal and Peri-anal warts are caused by ano-receptive sex, they are either not reported early either due to non-visualization or due to shame/guilt. The lesions can be handled easily when they are reported early. Presence of peri-anal lesions can cause cessation of sexual activity of patients, either through fear of transmission or embarrassment of lesions.

 

Causes of Anal warts

Anal warts are caused by a virus called the human papilloma virus (HPV).
HPV is one of the most common sexually transmitted disease (STD). There are more than 100 different types of HPV, which can infect and cause growth of warts in the different parts of the body. More than 90% of cases of peri-anal warts are caused by Human Papilloma Virus types 6 and 11. These two types do not cause cancer. It is not necessary to have an anal receptive intercourse to develop anal warts. HPV can transmit through direct contact exposure to the anal area (hand contact, secretions from a sexual partner) resulting in anal warts. Usually it takes months to develop anal warts after a HPV infection. The transmission of HPV does not necessitate clinical lesions to be present.
 

Cutaneous (skin) HPV types

Most HPV types are called cutaneous because they cause warts on the skin, such as on the arms, chest, hands, and feet. These are common warts, not genital warts.

 

Mucosal (Genital or Anogenital) HPV types

The other HPV types are considered mucosal types because they invade and live in cells on mucosal surfaces. The mucosal HPV types are also called genital (or anogenital) HPV types because they often affect the anal and genital area. These types can also infect the lining of the mouth and throat.   Mucosal HPV types generally don’t grow in the skin or parts of the body other than the mucosal surfaces but can involve anal and perianal skin surface as shown in the picture below. Mucosal (genital) HPV is spread mainly by direct skin-to-skin contact during vaginal, oral, or anal sexual activity. It’s not spread through blood or body fluids. It can be spread even when an infected person has no visible signs or symptoms.

  

Click for large image

Low-risk mucosal (genital) HPV types: HPV types that tend to cause warts and rarely cause cancer are called low-risk types. Low-risk genital HPV infection can cause cauliflower-shaped warts on or around the genitals and anus of both men and women. In women, warts may appear in areas that aren’t always noticed, such as the cervix and vagina.

 

High-risk mucosal (genital) HPV types: HPV types that can cause cancer are called high-risk types. These types have been linked to certain cancers in both men and women. Doctors worry about the cell changes and pre-cancers these types cause because they are more likely to grow into cancers over time6.

 
There is proven role of Human papilloma virus (HPV) is an etiologic factor in the development of penile cancer, penile intraepithelial neoplasia (PIN), anal cancer, and anal intraepithelial neoplasia (AIN).

Anyone who has had sexual contact can get HPV, even if it was only with only one person, but infections are more likely in people who have had many sex partners. 

The virus can also be spread by genital contact without sex, but this is not common. Oral-genital and hand-genital spread of some genital HPV types have been reported. And there may be other ways to become infected with HPV that aren’t yet clear.

You DO NOT get HPV from:

  • Toilet seats
  • Hugging or holding hands
  • Swimming in pools or hot tubs
  • Sharing food or utensils
  • Being unclean

Transmission from mother to newborn during birth is rare, but it can happen, too. When it does, it can cause warts (papillomas) in the infant’s breathing tubes (trachea and bronchi) and lungs, which is called respiratory papillomatosis. These papillomas can also grow in the voice box, which is called laryngeal papillomatosis. Both of these infections can cause life-long problems.

 

 

Risk Factors of Anal Warts

  • Multiple sexual partners
  • Anal receptive intercourse
  • Not using barrier contraceptives, such as condoms

 

 

Prevention of Anal Warts

Human papillomavirus vaccine is available that prevents the HPV infection and formation of anal warts.

Other preventive measures include:

  • Using condoms
  • Limiting sexual contact to a single partner
  • Sexual abstinence

Condoms can offer some protection from HPV infection, but HPV might be on skin that’s not covered by the condom. And condoms must be used every time, from start to finish. The virus can spread during direct skin-to-skin contact before the condom is put on, and male condoms don’t protect the entire genital area, especially for women. The female condom covers more of the vulva in women, but hasn’t been studied as carefully for its ability to protect against HPV. Condoms are very helpful, though, in protecting against other infections that can be spread through sexual activity.

It’s usually not possible to know who has a mucosal HPV infection, and HPV is so common that even using these measures doesn’t guarantee that a person won’t get infected, but they can help lower the risk 10.

 

Anogenital warts can now be effectively prevented using the quadrivalent (HPV 6, 11, 16 and 18) or nanovalent (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58) HPV vaccines; these protect against HPV types that cause anal/peri-anal/anogenital warts, cervical cancer and other types of anogenital and oral cancer. The Human Papilloma Virus (HPV) quadrivalent vaccine has shown to be up to 100% effective in preventing AGW in association with vaccine‐type HPV in women. The vaccine is also effective in 12‐ to 15‐year‐old boys and is licensed for use in both sexes. Evidence on whether the vaccination could be useful in anogenital warts treatment is not yet clear; however, there are scientific data supporting use of the vaccination in individuals previously exposed to HPV.

Click here for more details about HPV Vaccine 

 

Complications of Anal Warts

Anal warts are not life-threatening. If untreated, anal warts increase in size and can cause bleeding and discomfort. The risk of anal cancer also increases with some HPV subtypes 16 and 18. The risk of anal cancer is about 17 times higher in sexually active gay and bisexual men than in men who have sex only with women. Men who have HIV (human immunodeficiency virus) are also at higher risk of getting this cancer. Most cancers that are found in the back of the throat, including at the base of the tongue and in the tonsils, are HPV related due to oral sex.

 

Oral HPV infections - those persons doing oral sex like sucking and licking the sexual organs (cunnilingus/ fellatio/ anilingus/ rimming)  can develop oral HPV infections involving the oral cavity, throat, palate, tonsils and tongue. These HPV infections over long time can cause oral and throat cancers.

 

Diagnosis of Anal Warts

A detailed history regarding the sexual practices, anal receptive intercourse, and previous history of sexual transmitted diseases will be taken. Warts are diagnostic on appearance. Anal / peri-anal warts appear as papillomatous plaques or flat lesions and can be single or multiple in number. Lesions vary from flesh‐coloured to white, pink or brown. They typically manifest in areas of the body that are in close contact during sex: mainly on the anogenital areas such as vulva, penis, groin, perineum, perianal skin, Anal canal but also in the oral cavity (in case of oral sex). Diagnosis of clinically typical and does not require histological confirmation. DRE - Digital rectal examination is a must in Anal and Peri-anal warts to rule out intra-anal and rectal warts.

Proctoscopy is also performed to look for anal / rectal warts. In women, vaginal examination is important to rule out vaginal warts.
 
Polymerase chain reaction (PCR) for diagnosis of different HPV genotypes can be done by HPV fluid test in females or by lesion / wart biopsy in males.
 
There is no routine test for men to check for high-risk Human Papilloma Virus (HPV) strains that can cause cancer. However, and  anal Pap tests for gay and bisexual men can be done, who are at higher risk of anal cancer caused by HPV. In an anal Pap test, is done just like PAP test in females, wherein a spatula / brush is passed over anal canal and the cells isolated are sent for smear examination for any risk of malignant change.
 
Differential diagnoses that need to be excluded include normal skin variations (e.g. pearly penile papules, parafrenular glands, Fordyce spots, vestibular papillae, sebaceous cysts), other infectious or inflammatory conditions and other papules (syphilis on mucosal plates, molluscum contagiosum, lichen planus, psoriasis, condyloma lata) and benign or malignant neoplastic lesions (papillomatoses of vulva, nevi, verrucous carcinoma, invasive carcinoma, seborrhoeic keratosis, Bowen's disease, Buschke‐Löwenstein disease, pigmented or unpigmented grade 2–3 intraepithelial neoplasia, lymphangioma).

 

Patients should be reassured that if they have developed anal/ peri-anal / Ano-genital warts, appropriate treatment can clear the warts within 3 months. The anal/peri-anal lesions are of mostly sexual origin and are caused by Human Papilloma Virus (HPV) which is contagious; therefore, it is important for patients to disclose their recent sexual partners, who should be advised examination to rule out Human papilloma virus (HPV) infection. The smokers have a 27% increased risk of developing anal/peri-anal (ano-genital) warts as compared with non‐smokers. The HPV prevalence in patients who smoke is 48.2% compared with 37.5% for non‐smokers (P < 0.001). Generally, warts develop within weeks or months after acquiring Human Papilloma Virus (HPV) infection but in a significant number of cases, the virus can be dormant for months or years before warts emerge.

 

HPV Screening Through Anal Cytology

Though there is no guidelines for anal screening for HPV or anal cytology for anal cancer lesion (precancerous or abnormal anal canal cytology) but there is benefit if getting the anal Cytology for Anal cancer screening (similar to cervical cancer screening), using anal cytology (through canal brush cytology) followed by referral of patients with abnormal results to high-resolution anoscopy and subsequent treatment of biopsy-proved AIN (Anal canal Cancer in situ), may prevent the development of anal cancer.

The reported sensitivity and specificity of anal cytology relative to findings at biopsy (sensitivity, 69%-93%; specificity, 32%-59%, respectively) are similar to findings in studies comparing cervical cytology and cervical biopsy for the prevention of cervical cancer. There is definitive benefit to do annual anal cytology for MSM (men having sex with men) and any HIV-positive patients with a history of anogenital condylomas. Among patients with HIV- or HPV-related lesions, histologic signs of dysplasia are apparent in more than one-fifth of those who undergo testing. Among HIV-positive MSM (men having sex with men), the positive predictive value of abnormal anal cytology to predict anal dysplasia is approximately 95%.

Anal cytology can distinguish between the various stages of Anal Intra-epithelial neoplasia (AIN) 9.

  • Low-grade dysplastic cellular changes (AIN 1).
  • severe dysplasia (AIN 2)
  • Severe dysplasia and cancerous changes but no invasion (AIN 3), also known as carcinoma in situ, is diagnosed when 50% of the epithelial tissue is replaced with abnormal dysplastic cells.

 

Buschke–Lowenstein Tumor - Buschke–Lowenstein tumor, often called giant condyloma accuminatum, is considered by some authors as intermediate between condyloma and squamous cell carcinoma. Histologically, the tumor appears benign with papillomatosis, epithelial hyperplasia, and koilocytosis, but clinically it can behave aggressively with extensive infiltration. Typically, it is slow growing in immunocompetent individuals, but it can grow rapidly in immunocompromised individuals. Focally, these tumors can transform into invasive carcinoma; hence, early diagnosis and treatment is crucial. Common treatment approach includes radical surgical resection with tumor-free resection margins. Prophylactic HPV vaccination has been shown to reduce HPV6/11 infection and anogenital condylomata and thus is expected to prevent this tumor12, 13, 14.

 

Technique of anal Cytology for collecting the specimen

The goal of anal cytology is to identify patients with cellular changes in the epithelial cells that line the anal canal; any patients with atypia are then referred to undergo high-resolution anoscopy. No specific preparation is necessary before anal cytology, though patients should be instructed to refrain from receptive anal sex and enemas for 24 hours before testing. If a digital rectal examination is performed in conjunction with anal cytology, the cytologic sample must be obtained before lubrication is introduced into the anal canal. The standard technique used in obtaining anal cytologic specimens involves inserting a water-moistened Dacron swab into the anal canal to above the squamocolumnar transition zone, approximately 2 cm (1 inch) from the anal verge. While mild external pressure is applied to the anal wall, the swab is gently manipulated in a craniocaudal and circular motion within the canal. After several rotations, the swab should be withdrawn and immediately immersed in methanol-based preservative-transport solution.

 

High Resolution Anoscopy by high powered microscope (Anoscope / colposcope) for screening for intra-epithelial tumors of anal canal

The patient is put in jack knife position to expose anal canal. The anal canal is opened by inserting a Anal retractor (Czerny rectal speculum)

   

The anal canal is then screened segment by segment. The anal skin is treated with acetic acid 3% to see any aceto-white lesions and then treated with Lugol's iodine. Any area that does not take up the iodine is suspcious area and biopsy is taken from that area.

 

For more information about Pre-cancerous lesions of Anal Canal, Anal Intra-epithelial Carcinoma and Anal Cancer Click here

 

Treatment of Anal Warts

Treatment options include patient-applied (home-based) chemical treatments (podofilox, imiquimod), physician applied (office-based) chemical treatments (podophyllin, trichloracetic acid, interferon, green tea extract) and ablative treatments (cryotherapy, surgical removal, laser treatment). The main limitation of current therapies is the high recurrence rate after initial remission. The quadrivalent HPV vaccine demonstrated high efficacy in preventing the onset of HPV 6/11-related Ano-genital Warts in both males and females.

Treatment options are:

  • Topical medicines – putting cream or a liquid on to the warts (trichlorocetic acid, podophyllin, imiquimod).
  • Ablative techniques: Freezing (cryotherapy using liquid nitrogen), Electro-cautery (under local anaesthesia), Laser ablation (under local anaesthesia)
  • Surgical excision
  • Immuno-modulation

 

Untreated anal warts may grow and increase in size. It is, therefore, better to treat them and remove them. The treatment will depend on the size, number, and location of warts. For small warts. Untreated anal warts may grow and increase in size. It is, therefore, better to treat them and remove them. The treatment will depend on the size, number, and location of warts. 

Treatment should be individualized for each patient. Although untreated warts can resolve spontaneously, most patients want an immediate intervention to eradicate them. Treatments need to be selected on the basis of considerations such as the number, size, morphology, location and keratinization of warts, and whether they are new or recurrent.

 

Ablative techniques

Ablative techniques are commonly used to remove warts. The major frustration is the high rate of recurrence with these treatments and the need for repeat therapeutic interventions. Ablative techniques are associated with a risk of bleeding, tissue destruction, slow wound healing and scarring

 

Treatment Mode of action Schedule Clearance rate (%) Recurrence rate (%) Advantages Disadvantages
Ablative Techniques
             
Electrocautery High‐frequency electrical currents cause thermal damage to infected tissue Under local anaesthesia, base of lesion excised; repeat as required

90%

(Range:35–94%)

20%

(Range:20-25%)

90%

High recurrence rate is used alone but with immunomodulator creams the results are more than 90% remission rate

Repeat physician visits

Expertise required

Smoke evacuator needed
             
CO2 and Nd:YAG laser Laser vaporizes lesions Under local anaesthesia, protocol depends on type of laser

90%

(Range:23–95%)

 70%

(Range:2.5–77%)

Rapid results

Effective for thick lesions

High recurrence rate; in some cases even before healing of laser treatment

Costly

Substantial training & Expertise required

Pain/scarring

Smoke evacuator needed
             

 

 

Electrocautery or Cautery

Electrocautery uses high‐frequency electrical currents to destroy anal / peri-anal / anogenital lesions and requires local anaesthesia. Clinical studies have shown clearance rates of 35–94%.  As fumes from electrocautery contain contagious particles, preventative measures should be put in place to stop the virus spreading.

Electrofulgration/ electrocautery - will generate smoke/fumes which may contain human papillomavirus (HPV) particles that may be transmitted to the operator who breaths in or comes into contact with the fume. When working with HPV-related lesions, minimise the risk of transmission by -

  • Use smoke evacuator with intake nozzle 2 cm from operative site

  • Wear surgical mask (N95 is most effective) and eye protection.

 

 

Management of Ano-genital warts - part 2

Fulguration of Warts

Click here to watch this video of Fulgration of Warts on youtube

 

Management of Ano-genital warts - part 4

Fulgration of Intra-anal warts and peri-anal warts is demonstrated 

Click here to watch this video of management of Intra-anal warts on youtube

 

Laser ablation

Carbon dioxide (CO2) and Nd:YAG lasers, Argon Laser or other laser energies vaporize lesions using focused light energy; however, it is not always possible to know the extent of the infected tissue, and therefore, vaporizing large regions around the warts is not always feasible. Local anaesthesia is usually required, especially on extensive and thick lesions as it can penetrate deeply into the lesions. This treatment option is used less frequently than other therapies as it requires specialized and costly equipment, and has an increased risk of serious complications.  However, clearance rates of up to 95% have been reported in clinical studies, with a head‐to‐head comparison. It is important to note that fumes from laser treatment contain contagious particles and adequate measures should be taken to prevent the virus from spreading. Masks and smoke evacuators should therefore be used.

 

 

Surgical Management of Anal warts

 
Surgery is considered when anal warts are large or are located in the internal anus where it is difficult to apply local creams. Surgery is performed using scissors or scalpel and is particularly suited for removing large lesions causing obstruction. It can be done as an outpatient basis under local anaesthesia. (no admission is required). Though surgery is usually performed under local anesthesia but general anesthesia or spinal anesthesia may be given if warts are extensive. Clearance rates of up to 93% have been reported in clinical studies after surgical excision5.
 
In too extensive warts around anus with destruction of the anal skin or if there are dysplastic changes in the skin around anus with long standing warts (condyloma Acuminata) then one can go for excision of the skin with skin grafts or skin rotation flaps around anus7.
 
 
 
 
 

This is the clip showing surgical excision of the

Giant anal Warts (condyloma Acuminata) 

 

Click here to see this video of surgical excision of

Giant Anal warts (condyloma Acuminata) on youtube

 

 Topical Application Therapy


Treatment Mode of action Schedule Clearance rate (%) Recurrence rate (%) Advantages Disadvantages
Topical therapy
             
Trichloroacetic acid (33–50%) Acid induces a chemical burn

Applied directly to lesions;

repeat One to three times per week

  95%

(Range: 70 - 100%)

35%

(Range: 18-36%)

Rapid results

suitable for small lesions

High recurrence rate

Intense burning sensation
             
Podophyllotoxin 0.5% (alcoholic solution) 0.15% (cream) Antimitotic agent induces tissue necrosis Twice‐daily to affected areas for 3 consecutive days per week; discontinue for 4 days; repeat for up to 4 weeks

90%

(Range:45–95%)

100%

(Range:11-100%)

Easy self‐application

Very High recurrence rate

Complicated regimen

Intense application site reactions
             

 

Trichloroacetic acid (TCA; 33–50%)

Physician‐applied acidic treatment causes a chemical burn that destroys the Anal / peri-anal / ano-genital warts. The acid can be administered up to three times per week until the warts have cleared. This process requires a skilled professional to choose the appropriate lesion and duration of application but it is easy to apply and effective treatment. It has clearance rates of 70–100% reported in clinical studies. However, side‐effects such as local discomfort, burning and ulceration are common, hence the need for careful application. 

 

Podophyllotoxin 0.15% cream or 0.5% alcoholic solution

Podophyllotoxin stops division of infected cells causing tissue necrosis. It can be self‐applied by patients twice‐daily for three consecutive days, separated by a 4‐day treatment‐free period and repeated for up to 4 weeks. Patients need to carefully apply the solution to the lesions and avoid contact with healthy skin. Clearance rates from clinical studies range from 45 to 94%, with common side‐effects including pain, itching, burning, erosion and inflammation4.

 

 
 

Immunotherapies

 
Immunotherapies use stimulation of the body's own immune system to clear infected lesions.
 

Imiquimod 5% or 3.75%

Imiquimod is an immune response modifier with antiviral activity. This Toll‐like receptor 7 agonist induces the production of cytokines, which enhance the ability of antigen presenting cells to present viral antigens to reactive T lymphocytes. Imiquimod 5% has been approved for the treatment of anal/perianal/anogenital warts worldwide. Imiquimod 5% is self‐applied by the patient three nights per week for up to 16 weeks; if no improvement has occurred after 4–6 weeks, treatment can be applied daily. Imiquimod 5% may be applied for longer durations if there is a good clinical result but complete clearance has not occurred at the end of the initial treatment period. Imiquimod formulations are associated with local skin reactions such as erythema, pruritus, burning, pain and sometimes erosions. These are all signs that the immune system has been activated.  Clearance rates from clinical studies range from 35 to 75% with the 5% cream, with higher clearance rates in women than men.

Imiquimod is an immune response modifier that has potent antitumour and antiviral activity. It induces interferon-á, interleukin 1 (IL-1), and tumour necrosis factor á (TNF-á) in peripheral blood, and human keratinocytes exposed to imiquimod show an increase in mRNA for IL-2, IL-6, and IL-8. Wart clearance was associated with tissue production of interferons α, β and γ, and TNF-α 11.

 

Click here to know more about Imiquad (Imiquimod Cream) -  5% cream or 12.5 gm in 0.25gm cream sachet

 


 

Treatment Options

Anogenital warts recurrence is common and frustrating for patients and physicians. Recurrence rates with conventional ablative techniques are relatively high, since these methods only remove the visible wart without affecting the underlying HPV infection. Of currently available treatments, recurrence rates are very low with immunotherapies, imiquimod (6–19%) and sinecatechins (4–12%) as these treatments stimulate the host's immune response to clear the warts.

Studies have shown that a combination of ablative techniques followed by immunotherapy may lead to even lower recurrence rates; ablation provides rapid clearance but has high recurrence rates while immunotherapy has slow clearance rates and a lower risk of recurrence. 

Imiquimod 5% applied within 3 weeks after warts ablation (to ensure complete wound healing) was associated with a low rate of wart recurrence.

Pre‐treatment of Ano-genital warts with imiquimod to stimulate an immune reaction followed by surgery is also associated with low recurrence rates.

 

 

For other Misc. treatment options for anal warts click here

 

 

Follow Up

The anal warts can recur, even without sexual intercourse. HPV can hide in tissues for many months and can again cause new anal warts to grow. Therefore one may require a repeat treatment or surgery in case of recurrence.

 

Vaccination

Gardasil 9 is the most common vaccine used and is preventive against 9 HPV serotypes.

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

This vaccine can prevent most cases of cervical cancer if given before a girl or woman is exposed to the virus. In addition, this vaccine can prevent vaginal and vulvar cancer in women, and can prevent genital warts and anal cancer in women and men.

In theory, vaccinating boys against the types of HPV associated with cervical cancer might also help protect girls from the virus by possibly decreasing transmission. Certain types of HPV have also been linked to cancers in the mouth and throat, so the HPV vaccine likely offers some protection against these cancers, too

Dosage -
If it is begun before age 15, boys and girls get two doses of HPV vaccine; the second vaccination should be given six to 12 months after the first dose.
 
If it's not given by then, the CDC recommends girls ages 15 to 26 and boys ages 15 to 21 receive three doses; the last two should be given one or two and then six months after the first.
 
Gay, bisexual and other men who have sex with men, transgender individuals and immunocompromised persons (including those with HIV infection) up to age 26 should also receive the vaccine regimen, according to CDC recommendations.

 


 References
  1. O'Mahony C, Gomberg M, Skerlev M, et al. Position statement for the diagnosis and management of anogenital warts. J Eur Acad Dermatol Venereol. 2019;33(6):1006–1019. doi:10.1111/jdv.15570.
  2. Patel H, Wagner M, Singhal P, Kothari S. Systematic review of the incidence and prevalence of genital warts. BMC Infect Dis. 2013;13:39. Published 2013 Jan 25. doi:10.1186/1471-2334-13-39.
  3. McGinley KF, Hey W, Sussman DO, Brown GA. Human Papillomavirus Testing in Men. J Am Osteopath Assoc 2011;111(3_suppl_2):S26–S28.
  4. Nguyen AL, Quint KD, Bouwes Bavinck JN, Erceg A, de Kort WJA, Körver JEM. Real-life treatment of cutaneous warts with cantharidin podophyllin salicylic acid solution. Dermatol Ther. 2019 Nov;32(6):e13143. doi: 10.1111/dth.13143. Epub 2019 Nov 20. PMID: 31664756; PMCID: PMC6916542.
  5. Hyun JS, Kim GB, Choi BS, Kim MS, Park SG. Giant anal condyloma (giant condyloma acuminatum of anus) after allogeneic bone marrow transplantation associated with human papillomavirus: a case report. J Med Case Rep. 2015 Jan 19;9:9. doi: 10.1186/1752-1947-9-9. PMID: 25597932; PMCID: PMC4334849.
  6. Bastola S, Halalau A, Kc O, Adhikari A. A Gigantic Anal Mass: Buschke-Löwenstein Tumor in a Patient with Controlled HIV Infection with Fatal Outcome. Case Rep Infect Dis. 2018 Apr 1;2018:7267213. doi: 10.1155/2018/7267213. PMID: 29808133; PMCID: PMC5902119.
  7. Demirel AH, Ongoren AU, Bingül F, Gulcelik N. Total excision and V-Y plasty technique in the anal area condyloma acuminatum. Indian J Plast Surg. 2008 Jan;41(1):67-9. doi: 10.4103/0970-0358.41115. PMID: 19753205; PMCID: PMC2739560.
  8. Deshpande DJ, Nayak CS, Mishra SN, Dhurat RS. Verrucous condyloma lata mimicking condyloma acuminata: An unusual presentation. Indian J Sex Transm Dis AIDS. 2009 Jul;30(2):100-2. doi: 10.4103/0253-7184.62766. PMID: 21938129; PMCID: PMC3168050.
  9. Echenique I, Phillips BR. Anal warts and anal intradermal neoplasia. Clin Colon Rectal Surg. 2011 Mar;24(1):31-8. doi: 10.1055/s-0031-1272821. PMID: 22379403; PMCID: PMC3140331.
  10. McClean HL, Hillman RJ. Anogenital warts and condom use--a survey of information giving. Genitourin Med. 1997 Jun;73(3):203-6. doi: 10.1136/sti.73.3.203. PMID: 9306902; PMCID: PMC1195823.
  11. Eggleton S, Tang A. Management of difficult anogenital warts. Sex Transm Infect. 1999 Dec;75(6):449-50. PMID: 10754962.
  12. Bastola S, Halalau A, Kc O, Adhikari A. A Gigantic Anal Mass: Buschke-Löwenstein Tumor in a Patient with Controlled HIV Infection with Fatal Outcome. Case Rep Infect Dis. 2018 Apr 1;2018:7267213. doi: 10.1155/2018/7267213. PMID: 29808133; PMCID: PMC5902119.
  13. Yakan S, Cengiz F, Telciler KE, Uz M, Denecli AG. Rectal Involvement of Recurrent Buschke-Lowenstein Tumor Causing Subileus: a Case Report. Gastroenterology Res. 2011 Aug;4(4):177-179. doi: 10.4021/gr316w. Epub 2011 Jul 20. PMID: 27942337; PMCID: PMC5139731.
  14. Tas S, Arik MK, Ozkul F, Cikman O, Akgun Y. Perianal giant condyloma acuminatum-buschke-löwenstein tumor: a case report. Case Rep Surg. 2012;2012:507374. doi: 10.1155/2012/507374. Epub 2012 Nov 20. PMID: 23213594; PMCID: PMC3508531.
 

Warts Gallery (Videos about Warts Management)

 

 

Electro-coagulation / Fulgration (Electrosurgery) of Penile warts

Click here To see the video of Electro-coagulation / Fulgration of Penile warts on Youtube

 

 

 

Fulguration of anal Warts

Click here to see this video of fulgration of anal warts on youtube

 

 

 

.

Surgical Excision of Giant Anal Warts (condyloma Acuminata)

click here to see this video of surgical excision of Anal Condyloma Acuminata on youtube

 

 

 

 

Warts Gallery (Pictures / Diagrams about Warts and HPV virus)

 

HPV virus infection of the skin with warts formation and HPV virus shedding

 

Anal Warts - Longitudinal view

 

 

Anal Warts

 

anal Warts

 

 

Penile warts

 

 

 

 

Penile warts (Genital warts)

 

 


 

 

 

 

Anal Warts

Anal and Peri-Anal Warts   What are Anal Warts? Anal warts (condylomas) are small skin-colored or pink-colored growths or spots in or around the anus. These growths can become large and cover the entire anal area.   “ The word “condyloma” comes from the Greek word meaning “knob.” Any knob-like or warty growth on the genitals is known as a condyloma. The warts in HPV infection are called as condyloma acuminata or codyloma Acuminatum (while warts like growth in secondary syphilis is called as condyloma lata which can be confused with presentation of condyloma acuminata8). Anal warts are one of the most common sexually transmitted infections in world. They are caused by a small DNA virus, a papillomavirus belonging to the papovavirus group, which cannot be cultured. Genital warts differ from skin warts histologically and antigenically. Genital warts are nearly alwaystransmitted by sexual contact; autoinoculation from hand to genitals is unusual. The infectivity of sexually acquired warts is about 60%; the incubation period is long, varying from two weeks to eight months. Four distinct sub-types of Ano-genital warts have been described: condylomata acuminata (pointed warts), flat / macular lesions, papular, and keratotic lesions. The first two sub-types are mainly found on moist, non-keratinized epithelia, while the latter two usually present on keratinized epidermis. Ano-genital warts are also often referred to as genital warts, condylomata acuminata or genital verruca. Anal/ peri-anal/ Ano-genital warts are highly infectious; approximately 65% of individuals with an infected partner develop the lesions within 3 weeks and 8 months after exposure, the median time between infection with HPV types 6 or 11 and the development of warts was 11 to 12 months among males and 5 to 6 months among young females. In rare cases, Ano-genital warts can be associated with malignant lesions, namely Buschke-Lowenstein tumors.  …

    HPV Vaccine (Gardasil 9) warts

    GARDASIL 9 Vaccine - human papillomavirus (HPV) vaccine, 9-valent

     

    What is Gardasil 9 vaccine?

     

    Gardasil 9 (human papillomavirus (HPV)) vaccine is used in both females and males.

    Human papillomavirus (HPV) can cause genital warts, cancer of the cervix, anal cancer, and various cancers of the vulva or vagina.

    Gardasil 9 vaccine is used in girls and women ages 9 through 45 to prevent cervical/vaginal/anal cancers or genital warts caused by certain types of HPV.

    Gardasil 9 vaccine is also used in boys and men ages 9 through 45 to prevent anal cancer or genital warts caused by certain types of HPV.

    You may receive Gardasil 9 even if you have already had genital warts, or had a positive HPV test or abnormal pap smear in the past. However, this vaccine will not treat active genital warts or HPV-related cancers, and it will not cure HPV infection.

    Gardasil 9 vaccine prevents diseases caused only by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. It will not prevent diseases caused by other types of HPV.

    The Centers for Disease Control and Prevention (CDC) recommends HPV vaccine for all boys and girls ages 11 or 12 years old. The vaccine is also recommended in teenage boys and girls who have not already received the vaccine or have not completed all booster shots.

    Like any vaccine, the Gardasil 9 may not provide protection from disease in every person.

     

    Gardasil 9 vaccine will not protect against sexually transmitted diseases such as chlamydia, gonorrhea, herpes, HIV, syphilis, and trichomoniasis.

    You may feel faint during the first 15 minutes after receiving this vaccine. Some people have had seizure-like reactions after receiving this vaccine.

    Before taking this medicine

    To make sure Gardasil 9 vaccine is safe for you, tell your doctor if you have ever had:

    • an allergy to yeast, polysorbate 80, or to other vaccines;

    • a weak immune system (caused by conditions such as HIV or cancer); or

    • treatment with cancer medicine, steroids, or other drugs that can weaken your immune system.

    Tell your doctor if you are pregnant or plan to become pregnant. If you get pregnant before you receive all needed doses of this vaccine, you may need to wait until after your baby is born to finish the series of shots.

     

    How is Gardasil 9 vaccine given?

    Gardasil 9 vaccine is given as an injection (shot) into a muscle in your upper arm or thigh.

    Gardasil 9 vaccine is given in a series of 2 or 3 shots. You may have the first shot at any time as long as you are between the ages of 9 and 45 years. The second dose is given 2 to 6 months after your first shot. A third dose may be given 6 to 12 months after your first shot.

    Be sure to receive all recommended doses of this vaccine or you may not be fully protected against disease.

     

    Gardasil 9 Dosing Information

     

    Usual Adult Dose for Human Papillomavirus Prophylaxis

    Cervarix(R):
    Females, up to 25 years old: 0.5 mL, intramuscularly, at 0, 1, and 6 months

    Gardasil(R):
    Females and males, up to 26 years: 0.5 mL, intramuscularly, at 0, 2, and 6 months

    Gardasil 9(R):
    Females and males, up to 45 years: 0.5 mL, intramuscularly, at 0, 2, and 6 months

    Uses: For the prevention of cervical, vulvar, and anal cancer caused by Human Papillomavirus (HPV) in females, and prevention of anal cancer, genital warts, and anal intraepithelial neoplasia cause by HPV in males.

    Usual Adult Dose for Human Papillomavirus Prophylaxis:
    Aged 15 to 45 years: 0.5 mL, IM, at 0, 2, and 6 months.

    Usual Pediatric Dose for Human Papillomavirus Prophylaxis:

    Aged 9 to 14 years: 0.5 mL, IM, at 0, 2, and 6 months OR 0.5 mL IM, at 0 and a second dose between 6 and 12 months later.

    Uses: For the prevention of cervical, vulvar, and anal cancer caused by Human Papillomavirus (HPV) in females, and prevention of anal cancer, genital warts, and anal intraepithelial neoplasia cause by HPV in males.

    The next dose should be given as soon as possible. There is no need to start over.

     

    Gardasil 9 vaccine side effects

     

    Common Gardasil 9 side effects may include:

    Human papillomavirus vaccine Side Effects (Applies to human papillomavirus vaccine: intramuscular suspension)

     

    Side effects requiring immediate medical attention

    Along with its needed effects, human papillomavirus vaccine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

    Less common

    • Fever

    Incidence not known

    • Anxiety
    • back, leg, or stomach pains
    • bleeding gums
    • chest pain
    • chills
    • cough
    • dark urine
    • difficulty with breathing
    • difficulty with swallowing
    • dizziness or lightheadedness
    • fainting
    • fast heartbeat
    • general body swelling
    • headache
    • hives or welts, itching, or skin rash
    • loss of appetite
    • nausea
    • nosebleeds
    • pale skin
    • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
    • redness of the skin
    • seizures
    • sore throat
    • swollen, painful, or tender lymph glands in the neck, armpit, or groin
    • tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area
    • tightness in the chest
    • unusual tiredness or weakness
    • vomiting
    • yellowing of the eyes or skin
    Less common
    • Diarrhea

    • difficulty with moving

    • joint pain or swelling

    • muscle ache, cramps, pain, or stiffness

    • upper abdominal or stomach pain

    Rare

    • Body aches or pain

    • ear congestion

    • loss of voice

    • nasal congestion

    • runny nose

    • sneezing

    Incidence not known

    • Bloating

    • constipation

    • dark urine

    • difficulty with moving

    • indigestion

    • pain, swelling, or redness at the injection site

    • pains in the stomach, side, or abdomen, possibly radiating to the back

     

    For Healthcare Professionals

    Applies to human papillomavirus vaccine: intramuscular suspension

    General

    The most common adverse events were injection site reactions, fatigue, headache, and myalgia.[Ref]

    Local

    Very common (10% or more): Injection site pain (91.9%), injection site swelling (49%), injection site erythema (48.4%)

    Common (1% to 10%): Injection site pruritus, injection site hematoma, injection site induration, injection site hemorrhage, injection site warmth, injection site mass, injection site reaction

    Postmarketing reports: Injection site cellulitis

    Very common (10% or more): Fatigue (54.6%), headache (53.4%), pyrexia (13%), fever of 99.5F or higher (12.9%)

    Common (1% to 10%): Chlamydia infection, malaise

    Uncommon (0.1% to 1%): Death

     

    Musculoskeletal

    Very common (10% or more): Myalgia (48.8%), arthralgia (20.7%)

    Common (1% to 10%): Back pain

     

    Gastrointestinal

    Common (1% to 10%): Nausea, diarrhea, vomiting, abdominal pain upper, toothache

    Rare (less than 0.1%): Appendicitis, gastroenteritis

     

    Respiratory

    Common (1% to 10%): Nasopharyngitis, oropharyngeal pain, influenza, cough, nasal congestion, upper respiratory tract infection, pharyngitis

    Rare (0.01% to 0.1%): Pneumonia, pulmonary embolism, asthma

    Very rare (less than 0.01%): Bronchospasm

    Frequency not reported: Asthmatic crisis

     

    Nervous system

    Common (1% to 10%): Dizziness, migraine

    Rare : Acute disseminated encephalomyelitis, Guillain-Barre syndrome, motor neuron disease, paralysis, seizures, syncope (including syncope associated with tonic-clonic movements and other seizure-like activity) sometimes resulting in falling with injury, transverse myelitis

    Immunologic

    Common (1% to 10%): New medical conditions potentially indicative of systemic autoimmune disorders

     

    Hypersensitivity

    Common (1% to 10%): Injection site hypersensitivity

    Frequency not reported: Allergy to vaccine

     

    Hematologic

    Uncommon (0.1% to 1%): Lymphadenopathy

     

    Psychiatric

    Common (1% to 10%): Insomnia

     

    Genitourinary

    Common (1% to 10%): Dysmenorrhea, vaginal infection, urinary tract infection

    Rare (less than 0.1%): Pelvic inflammatory disease, pyelonephritis

     

    Dermatologic

    Common (1% to 10%): Rash, urticaria, itching/pruritus

     


    References

    1. "Product Information. Cervarix (human papillomavirus vaccine)." GlaxoSmithKline, Research Triangle Park, NC.

    2. "Product Information. Gardasil (human papillomavirus vaccine)." Merck & Company Inc, West Point, PA.

    3. Cerner Multum, Inc. "Australian Product Information."

    4. Cerner Multum, Inc. "UK Summary of Product Characteristics."

    5. "Product Information. Gardasil 9 (human papillomavirus vaccine)." Merck & Company Inc, Whitehouse Station, NJ.

     

    More product information about Gardasil Vaccine click here

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