The human papilloma virus (HPV) causes infections of the skin and mucous membranes. The locations and specific manifestations of infection depend on the type of virus and its mode of transmission. Many HPV strains are already spread during infancy and childhood through direct skin-to-skin contact and may remain dormant inside the cell, while others (especially HPV-1, HPV-2, and HPV-4) can cause common warts (verruca vulgaris). Other strains are sexually transmitted (especially in young adults) and can be further divided into low-risk and high-risk HPV types. Low-risk types (especially HPV-6 and HPV-11) can cause benign anogenital warts (condylomata acuminata) and papillomatous nodules in other genital (e.g., squamous intraepithelial lesions of the cervix) or non-genital (e.g., oral warts, respiratory papillomatosis) mucosal areas. Infection with oncogenic high-risk HPV types (especially HPV-16 and HPV-18) may lead to malignant disease. These high-risk strains account for more than 70% of cervical cancers and can also cause genital, oral, and oropharyngeal squamous cell cancers. Risk factors for infection include skin damage, immunocompromise, early first sexual intercourse, and frequent change of sexual partners. Most HPV infections are asymptomatic and self-limiting, although pruritus, tenderness, and bleeding may occur. Diagnosis is often based on the physical exam alone, but can be confirmed with diagnostic tests (e.g., PCR), particularly in asymptomatic HPV infections of the cervix. Treatment of condylomas includes the use of local ointments, cryotherapy, and electrocoagulation. However, surveillance is important since recurrence rates are high and malignant transformation is possible. Prevention includes education about safe sexual practices and the proper use of condoms, as well as vaccination of all persons 9–26 years of age.
Human papillomavirus 
- Double-stranded, circular, nonenveloped DNA virus with an icosahedral capsid
- Low-risk types 6 and 11
- High-risk types 16, 18, 31, and 33
- HPV types 1, 2, and 4: cause skin warts, such as common warts (verruca vulgaris) and plantar warts (myrmecias)
Route of transmission
- Transmission occurs between two epithelial surfaces.
- Close personal contact: cutaneous warts
- Sexual contact: anogenital lesions
Risk factors 
- Damaged skin/mucous membranes (e.g., maceration, trauma, herpes simplex virus infection)
- Immunodeficiency (e.g., HIV infection, chemotherapy)
- Additional risk factors for genital/mucosal HPV infections include:
- Unprotected sex
- Number of lifetime sexual partners
- Early age at first sexual activity
- Uncircumcised males
HPV expresses the following oncoproteins
- E6 → inhibition of p53 protein → inhibition of the intrinsic apoptotic pathway and inhibition of p21 protein
- Most common sexually transmitted infection (STI) 
- Approx. 50% of new infections affect individuals between 15–24 years of age. 
- Prevalence: ∼ 79 million in the US 
- Incidence: ∼ 14 million annually in the US 
Genital intraepithelial neoplasms
- (CIN) and
Condylomata acuminata (anogenital warts)
- Pathogen: HPV types 6 and 11 (responsible for ∼ 90% of genital warts) 
- Clinical features
- Visual inspection
- Application of 5% acetic acid turns lesions white (not a specific finding)
- Pathogen: : particularly HPV types 3 and 10
- Clinical features: flat, white-brown, slightly elevated, scattered plaques in the anogenital region
- Differential diagnosis: condylomata lata (usually flat, smooth, and moist) in syphilis
- Description: : transitional stage between a genital wart and Bowen disease (a squamous cell carcinoma in situ)
- Pathogen: : most commonly HPV-16
- Clinical features: multiple, flat, red-brown pigmented papules on the external genitalia (particularly the penile shaft, glans, foreskin, vulva, and perianal region)
- Re-examination every 3–6 months (lesions often regress spontaneously)
- If persistent: local destructive therapy (see “Treatment” of ““ above) followed by surveillance (annual examinations), since lesions may recur
- Prognosis: malignant transformation occurs in 2.6% of cases. 
Giant condylomata (Buschke-Löwenstein tumor)
Common warts (verruca vulgaris)
- Pathogen: : particularly low-risk HPV types 2 and 4
- Lesions are plaques or papules
- Often asymptomatic but may cause tenderness (depending on the location) and pruritus → scratching → bleeding
Plantar warts (verruca plantaris)
- Pathogen: particularly HPV types 1
- Clinical features
Flat warts (verruca plana)
- Pathogen: particularly HPV types3 and 10
- Multiple small, flat patches or plaques
- Localized on the face, hands, and shins
Nonanogenital mucosal manifestations
- Oral warts and oropharyngeal carcinomas
- Laryngeal papilloma: benign tumor of the laryngeal epithelium caused by HPV infection of the throat
- Laryngeal carcinoma
- Respiratory papillomatosis and squamous cell carcinoma (SCC) of the lung
- Conjunctival papillomas and conjunctival carcinoma
- Epidermal hyperplasia and hyperkeratosis
- See “.”
- Benign tumors, e.g., fibroids, papillomatous dermal nevi
- Molluscum contagiosum
- Malignant tumors, particularly squamous cell carcinomas
The differential diagnoses listed here are not exhaustive.
- There is no treatment for the infection itself.
- In most cases the infection clears up without any treatment
- Several factors guide the choice of the treatment of anogenital warts, including wart characteristics (i.e., size, number, and anatomic site), patient preference, and potential adverse effects.
- Treatment options of HPV–related anogenital warts are:
- Evidence of malignancy should always be excluded on HPV–related cervical lesions via cytological and histological monitoring.
- For treatment options of HPV–related cervical lesions, see “Treatment” in “ .”
- High rate of recurrence
- Infection with high-risk types may transition to precancerous or malignant lesions after several years. 
- Education about possible risk factors and effective preventive measures, such as: 
HPV vaccination 
- Recommended to all persons aged 9–26 years (routinely performed at 11–12 years of age because vaccination is most effective before exposure to HPV through sexual activity).
- Recommended for some adults aged 27–45 years based on a discussion of benefits and risks between the patient and the clinician (e.g., in order to complete the HPV vaccine series).
- Not licensed for use in adults aged > 45 years.
- See “Prevention” in “ .”
- Use of condoms: Condoms decrease the risk of infection but do not provide full protection, as uncovered areas may still be infected. 
- HPV vaccination 
Special patient groups
- Vertical transmission to the fetus is rare but may lead to:
- Vaccination should be avoided during pregnancy.
- Trichloroacetic acid is preferred
- Cryotherapy and surgical interventions are also safe.
- Podophyllin, 5-FU, and interferon are teratogenic and contraindicated in pregnancy.
- Cesarian section is indicated if the birth canal is obstructed by large genital warts.