What are the treatment options and management strategies for a patient who is Human Papillomavirus (HPV) positive?

Management of HPV-Positive Patients

For patients who test HPV-positive, management depends entirely on the clinical context: if genital warts are present, treat with cryotherapy or patient-applied topical therapy; if detected through cervical cancer screening, follow established colposcopy and surveillance protocols; and if no visible lesions exist, provide reassurance about the self-limited nature of most infections while ensuring age-appropriate cancer screening is current. 1

Understanding HPV Status and Prognosis

What HPV-Positive Means

• HPV infection is extremely common, with most sexually active adults acquiring HPV at some point in their lives 1
• The majority of HPV infections are transient and cleared by the immune system without causing clinical complications 2, 3
• HPV types 6 and 11 cause genital warts but are not associated with cancer 1
• High-risk types (particularly HPV-16 and HPV-18) are associated with cervical, anal, oropharyngeal, and other anogenital cancers 2, 4

Special Context: HPV-Positive Oropharyngeal Cancer

• If the patient has HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), this significantly improves survival time and is the single strongest prognostic factor for OPSCC 5
• HPV-positive tumor status impacts positively on overall survival and progression-free survival compared with HPV-negative OPSCC 5
• Patients with HPV-positive OPSCC may be candidates for less aggressive cancer treatments in ongoing clinical trials, potentially resulting in improved survival times and quality of life 5

Management Based on Clinical Presentation

For Visible Genital Warts

First-Line Treatment Options:

• Cryotherapy with liquid nitrogen is recommended as a provider-administered first-line treatment 1
• Patient-applied podofilox 0.5% solution or gel for external genital warts 1
• Imiquimod cream 5% applied 3 times per week (e.g., Monday, Wednesday, Friday) for up to 16 weeks until total clearance, applied before sleeping for 6-10 hours then washed off 6

Site-Specific Considerations:

• For vaginal warts: use cryotherapy with liquid nitrogen only (avoid cryoprobe due to vaginal perforation risk); TCA or BCA 80-90% can be applied weekly 1
• For urethral meatus warts: cryotherapy with liquid nitrogen or podophyllin 10-25% in compound tincture of benzoin 1
• For anal warts: cryotherapy or TCA/BCA 80-90%; intra-anal warts require specialist consultation 1

Important Treatment Considerations:

• Biopsy is indicated only for uncertain diagnosis, lesions unresponsive to standard therapy, worsening during therapy, immunocompromised patients, or pigmented/ulcerated lesions 1
• Type-specific HPV nucleic acid tests are not recommended for routine diagnosis or management of visible genital warts 1
• Recurrence is common (approximately 30%) regardless of treatment method 1

For Abnormal Cervical Cancer Screening Results

HPV-Positive with Normal Cytology:

• Return in 1 year for repeat testing if HPV type is not 16 or 18 5
• If HPV 16 or 18 positive, proceed directly to colposcopy even with normal cytology 5

HPV-Positive with Abnormal Cytology:

• ASC-US (atypical squamous cells of undetermined significance): If high-risk HPV DNA test is positive, refer immediately for colposcopy 5
• LSIL (low-grade squamous intraepithelial lesion) or higher: refer for colposcopy and directed biopsy 1
• HSIL (high-grade squamous intraepithelial lesion): expedited treatment is preferred for nonpregnant patients aged ≥25 years 5

Post-Treatment Surveillance:

• After treatment for high-grade precancer (CIN 2 or CIN 3), surveillance should continue for at least 25 years 5
• Initial testing includes HPV test or cotest at 6,18, and 30 months 5
• Long-term surveillance includes testing at 3-year intervals if using HPV testing or cotesting 5

For Asymptomatic HPV-Positive Patients Without Lesions

Screening Recommendations:

• All women with suspected HPV infection should have cervical cancer screening following standard age-appropriate guidelines 1
• Women should begin cytology testing within 3 years of beginning sexual activity or by age 21 years, whichever occurs first 5
• Female partners of HPV-positive patients should follow normal gynecological health guidelines, including routine cervical smears 5
• No follow-up is required for male partners in the absence of any standard HPV screening test available for men 5

Critical Counseling Points

Transmission and Partner Risk

• HPV is not spread through routine physical contact such as touching or kissing on the cheek or lips 5
• It is a contagious virus during common sexual activities 5
• Partners have likely already been exposed, and the risk of developing HPV-related cancer is extremely low 5
• No specific changes are required to sexual practice in established relationships 5
• After successful treatment of HPV-OPSCC, the probability of transmitting infection to future partners is negligible 5
• Correct and consistent condom use might reduce but does not eliminate transmission risk 1

HPV and Other Infections

• HIV and HPV are different viruses with no direct link 5
• Both can be transmitted through sexual behaviors, but becoming infected with HPV does not lead to HIV/AIDS 5
• HIV-infected patients with HPV infection are at increased risk for anal dysplasia and cancer 1

Lifestyle Factors

• Smoking is linked with increased prevalence of oral HPV infection and worse prognosis after adjusting for HPV tumor status and treatment 5
• The combination of smoking and alcohol consumption increases the risk of head and neck cancer in both HPV-seropositive and HPV-seronegative individuals 5
• Providers should screen for tobacco use and perform cessation counseling 5

Prevention Strategies

HPV Vaccination

• HPV vaccination is recommended for all individuals aged 9-26 years 1
• Ideally administered at 11 or 12 years of age before sexual debut 2
• Two-dose series if administered before 15 years of age; immunocompromised individuals require three doses 2
• Three vaccines are available: Gardasil (HPV 6,11,16,18), Cervarix (HPV 16,18), and Gardasil 9 (HPV 6,11,16,18,31,33,45,52,58) 5
• Vaccines are for prevention, not cure, of HPV and its related diseases 5
• HPV vaccines may also protect against oral HPV infection and related head and neck cancer 5

Barrier Protection

• Condom use might reduce the risk for HPV and HPV-associated diseases 5
• A study among newly sexually active college women demonstrated a 70% reduction in HPV infection when partners used condoms consistently and correctly 5
• Abstaining from sexual activity is the surest way to prevent genital HPV infection 5

Special Populations

Pregnancy

• Imiquimod, podophyllin, and podofilox should not be used during pregnancy 1
• Many experts advocate removal of genital warts during pregnancy as they can proliferate and become friable 1
• Cesarean delivery should not be performed solely to prevent HPV transmission to newborns 1

Immunocompromised Patients

• May not respond as well to therapy and may have more frequent recurrences 1
• Are at higher risk for squamous cell carcinomas arising in or resembling genital warts 1
• Require three doses of HPV vaccine regardless of age at initiation 2
• Biopsy is indicated for uncertain or concerning lesions 1

When to Refer to Specialists

OB-GYN Referral Indicated For:

• Women with abnormal cervical cytology requiring colposcopy 1
• Patients with cervical warts 1
• Patients with extensive or treatment-resistant warts 1
• Immunocompromised patients with concerning lesions 1

Specialist Consultation For:

• Intra-anal warts requiring management 1
• HPV-positive oropharyngeal cancer for multidisciplinary treatment planning 5

Common Pitfalls to Avoid

• Do not assume HPV infection indicates sexual infidelity, as the virus can remain dormant for long periods 1
• Do not use HPV DNA testing for screening in men, partners of women with HPV, or adolescent females 1
• Do not use acetic acid soaks as a screening test for subclinical HPV infection due to high false-positive rates 1
• Do not perform routine surveillance for HPV infection or partner notification, as these are not useful for HPV prevention 5
• Do not confuse low-risk HPV types (causing warts) with high-risk types (causing cancer) when counseling patients 1