What are the recommended prevention, screening, and management strategies for human papillomavirus infection, including vaccination schedule, cervical cancer screening, treatment of genital warts, and care of cervical intra‑epithelial neoplasia?

HPV: Prevention, Screening, and Management

Vaccinate all children at age 11-12 years with HPV vaccine (either sex), screen women starting at age 21 with cervical cytology, treat genital warts with patient-applied or provider-administered therapies, and manage cervical intraepithelial neoplasia with excisional or ablative procedures based on grade and persistence. 1, 2

Vaccination Strategy

Routine Vaccination Schedule

• Administer HPV vaccine routinely at ages 11-12 years for both girls and boys (can start as early as age 9) 1, 2
• For ages 9-14 years: Use 2-dose schedule at 0 and 6-12 months (if second dose given before 5 months, administer third dose at least 4 months later) 2
• For ages 15-26 years: Use 3-dose schedule at 0,2, and 6 months 2

Vaccine Coverage and Efficacy

• The 9-valent vaccine (Gardasil 9) protects against HPV types 6,11,16,18,31,33,45,52, and 58, covering approximately 90% of genital warts and 70% of cervical cancers 1, 2
• Vaccine efficacy is 100% in preventing persistent type-specific infections and CIN2/3 in protocol-adherent, previously uninfected individuals 1
• Vaccination is most effective when all doses are administered before sexual contact 1

Special Populations

• Vaccinate MSM, people living with HIV/AIDS, and immunocompromised persons through age 26 years 1
• Catch-up vaccination recommended for females through age 26 and males through age 21 if not previously vaccinated 1

Cervical Cancer Screening

Screening Initiation and Intervals

• Begin cervical cancer screening at age 21 years regardless of sexual activity onset 1
• Women aged 21-29 years: Pap test every 3 years 1
• Women aged 30 years and older: Either Pap test every 3 years OR co-testing (Pap + HPV) every 5 years 1

HPV Testing Context

• HPV DNA testing is FDA-cleared only for cervical specimens collected during clinical examinations, not for self-testing or routine STD screening 3
• Use HPV testing for triage of abnormal Pap results in women ≥21 years and as adjunctive testing with cytology for women ≥30 years 3
• Do NOT use HPV testing for: screening men, partners of HPV-positive women, adolescent females, or conditions other than cervical cancer 1, 3

Management of HPV-Positive, Cytology-Negative Results

• Option 1: Repeat co-testing at 12 months; refer to colposcopy if either test positive 4
• Option 2 (Preferred): Immediate colposcopy for HPV-16 or HPV-18 positive results due to markedly higher short-term risk of CIN3 or cancer 4, 3
• Do NOT refer all HPV-positive women to colposcopy without genotype information, as overall short-term CIN3 risk in HPV-positive, cytology-negative women falls below the threshold for immediate evaluation 4

Critical Pitfall: HPV-16 accounts for 50-60% of invasive squamous cell carcinomas worldwide and shows the highest persistence rate among high-risk types 1, 4. The longer an HPV infection persists, the lower the probability of subsequent clearance 4.

Natural History and Counseling

Infection Clearance

• Approximately 70% of new HPV infections clear within 1 year and 90% within 2 years in immunocompetent adults (median duration 8 months) 4
• In men, median clearance time is 6 months, with 75% clearing within 12 months 4
• Most low-grade lesions resolve spontaneously: 75% in adults and 90% in adolescents 1

Key Counseling Messages

• HPV infection is extremely common; most sexually active adults will acquire HPV at some point, though most never know it 1
• Within an ongoing sexual relationship, both partners are usually infected when one is diagnosed, even without visible signs 1
• HPV diagnosis in one partner does NOT indicate sexual infidelity in the other 1
• The types causing genital warts (HPV-6,11) differ from those causing cancer (HPV-16,18, and others) 1
• Condom use might lower transmission chances but is not fully protective, as HPV can infect areas not covered by condoms 1

Treatment of Genital Warts

Patient-Applied Therapies

• Imiquimod 3.75% cream (newer formulation recommended for anogenital wart treatment) 1
• Imiquimod 5% cream (alternative formulation) 5
• Sinecatechin (green tea extract) 10% ointment in Europe, 15% in USA 5

Provider-Administered Therapies

• Cryotherapy with liquid nitrogen 1
• Electrocautery 1
• Laser therapy 1
• Surgical excision 1

Treatment Expectations

• If left untreated, genital warts may resolve spontaneously, remain unchanged, or increase in size/number 1
• Genital warts commonly recur after treatment, especially in the first 3 months 1
• Genital warts are NOT life-threatening and will NOT turn into cancer except in very rare cases 1

Critical Pitfall: Perform laser or electrocautery in well-ventilated rooms using standard precautions to prevent possible HPV transmission to healthcare workers 1.

Management of Cervical Intraepithelial Neoplasia

Treatment Modalities

• Excisional procedures: Loop electrosurgical excision procedure (LEEP), cold knife conization, laser conization 1
• Ablative procedures: Cryotherapy, laser ablation 1

Post-Treatment Surveillance

• Continue surveillance for at least 25 years after treatment for high-grade precancer 3
• Perform post-treatment testing at 6,18, and 30 months 3

Grade-Specific Considerations

• CIN1 (low-grade): Often resolves spontaneously; observation is appropriate in most cases 1
• CIN2/3 (high-grade): Requires treatment due to significant cancer progression risk 1

Special Considerations

Anal Cancer Screening

• Insufficient data to recommend routine anal cytology screening in HIV-positive persons or HIV-negative MSM 1
• Annual digital anorectal examination may be useful for early detection in these high-risk populations 1

Pregnancy and Fertility

• HPV does NOT affect a woman's fertility or ability to carry a pregnancy to term 1

Vaccination Does NOT Eliminate Screening

• Women who receive HPV vaccine must continue cervical cancer screening per standard of care 2
• Vaccination does NOT protect against disease from HPV types to which a person was previously exposed 2
• Vaccination does NOT treat existing HPV infections, genital warts, or precancerous lesions 2