Human papillomavirus

Growing 2
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Diagnosis and reasoning

The differential diagnosis of penile growths is broad, and encompases both infectious and noninfectious conditions. The main infective conditions are genital warts (caused by Human Papillomavirus - HPV), condyloma lata (due to secondary syphilis), bowenoid papulosis and molluscum contagiosum. Non-infective growths include dermatological conditions such as seborrheic keratoses, pearly penile papules and lichen planus, as well as skin tags and sebaceous cysts. In this patient, the diagnosis is very straightforward - the cauliflower like appearance of the growths is typical of genital warts. As the diagnosis is obvious, there is no value in performing a biopsy. Note also that currently, not only are there are no HPV DNA tests recommended for men, but DNA testing is not performed in the diagnostic workup anyway. Anoscopy is indicated in patients who have engaged in anal intercourse, as they are at increased risk for anal intraepithelial neoplasia and anal squamous cell cancer. VDRL is not useful as a diagnostic investigation - but should be performed to screen him for syphilis (as these patients may have other concomitant STIs). The warts can be treated with cryotherapy; circumcision is unnecessary in this patient. There is no role for Penicillin or Acyclovir in his current management. Further diagnostic discussion In many patients with genital warts, the diagnosis is not as straightforward. Aside from the above cauliflower like appearance, genital warts may also assume three other forms: smooth papular warts, keratotic warts and flat warts. The other conditions which give rise to smooth papular growths include Bowenoid papulosis (where there may be dome shaped or flat topped papules with a hyperpigmented or bluish hue); pearly penile papules and molluscum contagiosum. The differential diagnosis of keratotic growths include seborrheic keratosis (where there are raised verrucous lesions which are brown or black in color); and lichen planus (where there are raised itchy lesions which are characterized by a violaceous appearance). Condyloma lata (which is a manifestation of secondary syphilis) typically appears as a moist, flat and smooth lesion. Bowenoid papulosis may also present as plaques (which are formed by the coalescence of several smaller papules). Thus, it may at times be difficult to make the diagnosis of genital warts based on physical characteristics alone - in such a scenario, biopsy and histological analysis plays a role in the diagnosis.


Discussion

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. The most important subtypes are HPV 6 and 11, which cause genital warts, and HPV 16 and 18 which cause intraepithelial neoplasia and cancers of the genital tract. Up to 79% of sexually active women acquire a genital HPV infection during their lifetime, with the highest prevalence in those between 18 to 24 years of age. The incidence then declines with age, until a second peak is reached in the postmenopausal years. The main risk factors for the disease include an early age of first sexual intercourse, a high number of sexual partners, acquisition of new partners and lack of condom use. Male circumcision is considered to be protective against HPV. Most infections are subclinical, with approximately 70% of incident infections clearing within a year; symptomatic disease commonly manifests as anogenital warts, which usually develop around 2 to 3 months after infection. The warts typically occur at the vaginal introitus, under the foreskin in uncircumcised men, and on the penile shaft in circumcised men. Most patients only complain of the lesions but there may be other symptoms such as itching, bleeding and physical discomfort. Note that intra-anal warts can occur with or without receptive anal intercourse. In a minority of patients who fail to clear the HPV infection, progression to intraepithelial neoplasia and malignancy can occur. Note that HPV types 16 and 18 are responsible for approximately 70% of all cervical cancers; and 40% of all penile tumors are attributable to infection with HPV. The diagnosis of genital warts is usually clinical, but biopsy is indicated if the lesions are atypical, pigmented, indurated, fixed or ulcerated, if the patient is immunocompromised, or if they do not respond to therapy or worsen during therapy. Application of 3% to 5% of acetic acid to the genital mucosa (to detect infection) is not routinely recommended as this is nonspecific. In addition, in females, testing of the warts for HPV DNA is not recommended as this will not alter the management. Note that in males, there is no standardized DNA test in this regard. The warts may be treated via topical or surgical techniques. Topical methods include application of podofilox or imiquimod (which can be done by the patient himself); and cryotherapy and application of trichloroacetic acid (which is performed by a healthcare provider). Surgical techniques include surgical excision, electrosurgery, curettage and laser surgery Unfortunately, there is a 20% to 30% recurrence rate, regardless of the modality of treatment. On the topic of prevention, it should be noted that there are 2 HPV vaccines which are highly effective in preventing the disease. However, these are mainly effective when administered prior to any sexual contact.


Take home messages

  1. HPV is the most common STD worldwide - and is asymptomatic in many patients.
  2. The diagnosis of genital warts is mainly clinical. However, biopsies may be indicated in atypical lesions.
  3. Certain topical treatments may be administered by the patient himself, at home.

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  1. Am Fam Physician. 2004 Dec 15;70(12):2335-2342,Management of Genital Warts, Charles M. Kodner, M.D., and Soraya Nasraty, M.D.
  2. Am Fam Physician. 2010 Nov 15;82(10):1209-1214, Human Papillomavirus: Clinical Manifestations and Prevention, Gregory Juckett, MD, MPH, and Holly Hartman-Adams, MD.
  3. Centers for Disease Control and Prevention: Sexually Transmitted Diseases Treatment Guidelines, 2010: Genital warts.
  4. Gynecologic Oncology (impact factor: 3.89). 05/2010; 117(2 Suppl):S5-10, doi:10.1016/j.ygyno.2010.01.024, Pathology and epidemiology of HPV infection in females, Margaret Stanley.
  5. Prev Med. 2011 October; 53(Suppl 1): S36–S41, doi: 10.1016/j.ypmed.2011.08.002, Genital HPV infection and related lesions in men, Gabriella M. Anic and Anna R. Giuliano.