What is Human Papillomavirus (HPV) and how is it prevented and treated?

Human Papillomavirus (HPV): Overview, Prevention, and Management

What is HPV?

HPV is the most common sexually transmitted infection worldwide, with over 200 identified types that infect epithelial cells of the skin and mucous membranes. 1, 2 Approximately 15 types are oncogenic (cancer-causing), with HPV types 16 and 18 being the most clinically significant. 3, 4

Key Epidemiologic Facts

• At least 50-80% of sexually active individuals will acquire HPV at some point in their lifetime, with an estimated 20 million Americans currently infected and over 6 million new infections annually. 5, 1
• More than 50% of college-age women acquire HPV within 4 years of first intercourse. 5
• Point prevalence among young women ranges from 27% to 46%. 5
• Almost half of all infections occur in individuals aged 15-25 years. 5

HPV Types and Associated Diseases

High-risk oncogenic types (particularly HPV-16 and HPV-18):

• Cause virtually all cervical cancers (HPV-16 accounts for 50-60%, HPV-18 for 10-15% of invasive squamous cell carcinomas). 5
• Responsible for 80-90% of anal cancers, at least 40% of vulvar cancers, and variable proportions of vaginal, penile, and oropharyngeal cancers. 5, 4, 6
• Approximately 4.5% of all human malignancies are attributable to HPV. 6

Low-risk types (HPV-6 and HPV-11):

• Cause approximately 90% of anogenital warts (over 500,000 new cases annually in the US). 5
• Associated with juvenile laryngeal papillomatosis in rare cases. 5

Natural History and Transmission

Infection Course

Most HPV infections are transient and resolve spontaneously within 1-2 years, even with high-risk types. 5 Key progression facts:

• 75% of low-grade lesions in adults and 90% in adolescents resolve without treatment. 5
• Persistent infections (those that don't clear) carry the greatest risk for developing precancerous lesions and cancer. 5
• The stepwise progression from HPV acquisition to invasive cancer takes an average of 20 years, providing ample opportunity for screening and intervention. 5
• HPV-16 is unique in being most likely to persist and progress to high-grade cervical intraepithelial neoplasia (CIN3). 5

Transmission Routes

• Primary transmission occurs through vaginal, anal, or oral sexual contact, including skin-to-skin genital contact without penetration. 5, 2
• Vertical transmission from mother to newborn is relatively uncommon but can cause respiratory papillomatosis. 5
• Oral-genital and hand-to-genital transmission is plausible but remains incompletely proven. 5

Prevention Strategies

HPV Vaccination: The Primary Prevention Method

All children should receive routine HPV vaccination at age 11-12 years (can start as early as age 9), bundled with other adolescent vaccines (Tdap and MCV4), with completion of the series by the 13th birthday for greatest effectiveness. 5, 7, 8

Vaccine Types and Coverage

The nonavalent vaccine (9vHPV, Gardasil 9) is the current standard, providing protection against HPV types 6,11,16,18,31,33,45,52, and 58, potentially preventing approximately 90% of cervical and other HPV-related cancers. 7, 8, 3

• Three vaccines have been licensed: bivalent (2vHPV), quadrivalent (4vHPV), and nonavalent (9vHPV). 7, 3
• All three vaccines show similar efficacy against HPV 16/18, but the nonavalent provides additional protection against five other high-risk types. 3

Dosing Schedule

• For individuals under 15 years: Two-dose series (0 and 6-12 months apart). 7
• For individuals 15 years and older: Three-dose series (0,2, and 6 months). 7
• Minimum interval: 4 weeks between doses 1 and 2; 12 weeks between doses 2 and 3. 7
• Immunocompromised individuals require three doses regardless of age. 1

Catch-Up Vaccination

• Females: Recommended through age 26 years if not previously vaccinated. 7, 8
• Males: Recommended through age 21 years (through age 26 for men who have sex with men and immunocompromised persons). 5, 7, 8

Vaccine Efficacy and Safety

• Vaccines are highly effective when administered before HPV exposure, with demonstrated protection for at least 5 years without waning. 7, 3
• Critical caveat: Vaccination does not protect against HPV types already present at the time of vaccination, but still provides protection against other vaccine-targeted types. 7, 8
• Vaccines are safe, with the most common adverse effects being local injection site reactions. 3
• Can be administered to breastfeeding women and immunocompromised individuals. 7

Behavioral Prevention

Abstaining from sexual activity is the most effective way to prevent genital HPV infection. 5, 8 For sexually active individuals:

• Consistent and correct condom use reduces HPV transmission risk by approximately 70%, though skin not covered by condoms remains vulnerable. 5, 7, 8
• Monogamous relationships with uninfected partners reduce future infection risk. 8
• Limiting number of sexual partners decreases exposure risk. 1

Screening for HPV-Related Disease

Cervical Cancer Screening

All women should begin cervical cancer screening with Pap testing within 3 years of sexual activity initiation or by age 21 years, whichever comes first. 7, 8

• Women aged 30 years and older with three consecutive normal Pap tests should be screened every 2-3 years. 7, 8
• HPV DNA testing in conjunction with cytology is recommended as a screening option for women aged 30 and older. 5
• If both Pap and HPV testing are negative in women over 30, screening intervals can be extended to 3 years. 8

Screening Success and Limitations

• Cytology-based screening programs have reduced cervical cancer incidence by 60-90% within 3 years of implementation. 5
• US cervical cancer incidence decreased 75% and mortality by 74% in the 50 years following Pap test introduction. 5
• Critical pitfall: 50% of women who develop cervical cancer have never been screened, and another 10% haven't been screened within 5 years of diagnosis. 5

Other Screening Considerations

• Data are insufficient to recommend routine anal cancer screening with anal cytology, even in high-risk populations (HIV-positive individuals, men who have sex with men). 8
• Annual digital anorectal examination may be useful for early detection in high-risk populations. 8

Management of HPV Infection and Related Conditions

Counseling for Positive HPV Tests

When disclosing a positive high-risk HPV test, provide the following information:

• HPV is extremely common—most sexually active persons acquire it at some time, though most never know it. 5
• Detection of HPV does not indicate infidelity or recent sexual activity, as infection can persist for years before detection. 5
• No clinically validated test exists for men to determine HPV infection status. 5
• Sexual partners of HPV-infected individuals likely already have HPV, even without symptoms. 5, 8
• A normal Pap test with positive HPV indicates no current cellular abnormalities but requires follow-up monitoring. 5

Treatment of HPV-Related Lesions

There is no treatment for HPV infection itself—management focuses on treating visible lesions and precancerous changes. 8

Genital Warts

• Podofilox 0.5% topical solution is FDA-approved for external genital warts (not for perianal or mucous membrane warts). 9
• Imiquimod 3.75% cream is also recommended. 8
• Other options include cryotherapy, electrocautery, laser therapy, and surgical excision. 8

Cervical, Vaginal, and Vulvar Precancers

• Treatment includes cryotherapy, electrocautery, laser therapy, and surgical excision. 8
• If abnormal cervical cytology is detected, follow-up is essential to prevent progression. 5

Special Populations

HIV-Infected Individuals

• HPV vaccination is recommended for all HIV-infected males and females aged 11-12 years (or 13-26 years if not previously vaccinated) using a 3-dose series. 8
• HIV-infected men who have sex with men are at increased risk for anal dysplasia and cancer. 8
• If anal cytologic screening shows abnormalities, high-resolution anoscopy with biopsy should be performed. 8

Disparities in Cervical Cancer Burden

Cervical cancer incidence remains 60% higher among Black women (10.5/100,000) compared with White women (6.6/100,000), with the highest mortality among Black women (4.7/100,000). 5 High-risk groups include:

• African Americans in the rural South and urban areas
• Hispanics along the US-Mexico border
• White women in Appalachia and rural areas
• American Indian/Alaska Native women
• Vietnamese Americans 5

These disparities result from limited healthcare access, resources, and social/cultural barriers. 5

Critical Pitfalls to Avoid

• Never assume vaccination eliminates the need for screening—all women should continue screening regardless of vaccination status. 5
• Partner notification is not useful for HPV prevention due to the infection's high prevalence and likelihood that partners are already infected. 8
• Smoking increases oral HPV infection prevalence and worsens prognosis for HPV-related cancers. 8
• Vaccination rates in the US lag far behind other high-income countries, representing a missed opportunity for cancer prevention. 5

The Path to Elimination

The combination of HPV vaccination and cervical cancer screening has the potential to eliminate cervical cancer as a public health problem. 5 Vaccination of all children aged 9-12 years can prevent over 90% of HPV-related cancers (cervical, oropharyngeal, anal, vaginal, vulvar, and penile), potentially leading to the first elimination of a cancer in history. 5 Approximately 28,500 cancers could be prevented annually in the US through HPV vaccination. 5