What are the clinical manifestations of human papillomavirus (HPV) infection and the recommended treatment options?

HPV Symptoms and Clinical Manifestations

Most HPV infections are completely asymptomatic and unrecognized, with the majority clearing spontaneously within 8-24 months without any clinical manifestations. 1, 2

Asymptomatic Infection (Most Common Presentation)

• The vast majority of HPV infections produce no visible signs or symptoms and are detected only through screening tests or serologic studies 1
• Most sexually active persons will acquire HPV at some point, with up to 92% of young sexually active women having evidence of infection, yet most remain completely unaware 1
• Asymptomatic infections can persist for years before detection, and most clear spontaneously within 8 months (median duration), with only 9% persisting beyond 24 months 2

Low-Risk HPV Types (6 and 11) - Genital Warts

When symptomatic, low-risk HPV types 6 and 11 cause visible genital warts (condyloma acuminatum), accounting for approximately 90% of all genital wart cases. 3, 4

Clinical Features of Genital Warts:

• Visible flesh-colored or cauliflower-like growths on external genitalia (penis, vulva, scrotum, perineum, perianal skin) 1, 4
• Can occur on cervix, vagina, urethra, anus, mouth, and rarely conjunctiva, nose, or larynx 1
• Most commonly asymptomatic, but may be painful, friable (easily bleeding), or pruritic (itchy) depending on size and location 1
• Intra-anal warts occur predominantly with receptive anal intercourse, while perianal warts can occur without anal sex history 1
• Diagnosis is made by visual inspection alone in typical cases; biopsy only needed if diagnosis uncertain, lesions don't respond to treatment, disease worsens, patient immunocompromised, or warts are pigmented, indurated, fixed, or ulcerated 3

High-Risk HPV Types (16,18,31,33,35) - Precancerous and Cancerous Lesions

High-risk HPV types are strongly oncogenic and cause cervical intraepithelial neoplasia (CIN) and cancer, but these lesions are typically asymptomatic until advanced stages. 1

Cervical Manifestations:

• HPV infection of the cervix is usually completely asymptomatic and detected only through Pap test screening 1
• Cervical intraepithelial neoplasia (CIN) grades 1,2, or 3 represent increasing degrees of abnormality 1
• HPV types 16 and 18 account for approximately 68% of squamous cell cervical cancers and 83% of adenocarcinomas 1
• CIN 1 clears spontaneously in 60% of cases and rarely progresses to cancer (1%); CIN 2/3 clears in only 30-40% and progresses to cancer in >12% if untreated 1

Other Anogenital Cancers:

• High-risk HPV types cause vulvar, penile, anal, vaginal, and oropharyngeal cancers 1, 4, 5
• These cancers are typically asymptomatic in early stages 4, 5
• Most cases of cervical, anal, and oropharyngeal cancers worldwide are due to persistent HPV infection 5

Rare Manifestations

• Recurrent respiratory papillomatosis (RRP) can occur from vertical transmission during childbirth, causing laryngeal warts 1
• Juvenile-onset recurrent oral and respiratory papillomatosis (JORRP) in neonates from vertical transmission 6

Subclinical Infection Symptoms

• Some patients with subclinical HPV infection (not visible warts) report burning, fissuring, and dyspareunia (painful intercourse) 2
• These symptoms warrant evaluation and potential treatment only if symptomatic 2

Treatment Approach

The primary goal of treatment is removal of symptomatic visible warts, not eradication of HPV infection itself. 1, 3

For Visible Genital Warts:

• First-line options include patient-applied topical agents or provider-administered destructive therapies 3
• Cryotherapy with liquid nitrogen is a recommended provider-administered option 3
• Surgical excision is recommended for oral lesions and can be used for genital lesions 3
• If left untreated, genital warts may resolve spontaneously, remain unchanged, or increase in size/number 1

For Cervical Dysplasia:

• Treatment involves removing abnormal cells through procedures like LEEP, cryotherapy, or cone biopsy, with close follow-up for recurrence 7
• Regular cervical cancer screening with Pap tests is essential for detecting precancerous changes 1

Prevention

HPV vaccination (Gardasil) is highly effective when administered before sexual debut, protecting against HPV types 6,11,16, and 18. 3, 4

• Vaccine prevents 90% of genital warts (types 6 and 11) and 70% of cervical cancers (types 16 and 18) 3
• Recommended for girls and young women aged 9-26 years, even those previously diagnosed with HPV 1
• Consistent condom use reduces but does not eliminate transmission risk, as skin-to-skin contact of uncovered areas can transmit HPV 1