What are the recommended follow-up steps for a [AGE] year old woman who is Human Papillomavirus (HPV) positive but has normal cytology results?

Management of HPV-Positive with Normal Cytology

For an HPV-positive patient with normal cytology, repeat co-testing (HPV and cytology) at 12 months is the recommended management, with colposcopy reserved only if HPV remains positive or cytology becomes abnormal at follow-up. 1, 2

Age-Specific Considerations

The management approach depends critically on the patient's age:

• If age ≥30 years: Proceed with the 12-month repeat testing strategy described below 1, 2
• If age 21-29 years: HPV testing should not be used for routine screening in this age group, as HPV prevalence is extremely high and most infections clear spontaneously 1
• If age <21 years: HPV testing is not recommended at all 1, 3

HPV Genotype-Specific Management

The specific HPV genotype determines immediate management:

HPV 16 or 18 Positive

• Immediate colposcopy is required regardless of normal cytology 1, 2
• HPV 16 carries a 17-21% 10-year cumulative risk of CIN3+ 2
• For HPV 18, endocervical sampling should be performed at colposcopy due to its association with adenocarcinoma 1, 2

Other High-Risk HPV Types (Non-16/18)

• Return in 12 months for repeat co-testing 1, 2
• These women have only a 1.5-3% risk of CIN3+, which is below the threshold for immediate colposcopy 2
• Approximately 60% of high-risk HPV infections clear spontaneously within one year 2

Follow-Up Protocol at 12 Months

At the 12-month follow-up visit:

• If both HPV and cytology are negative: Return to routine age-based screening (typically every 3 years for co-testing) 2
• If HPV remains positive (regardless of cytology): Proceed to colposcopy with endocervical sampling 2
• If cytology shows any abnormality (regardless of HPV status): Proceed to colposcopy according to cytology-based management guidelines 2

Rationale for Conservative Management

The evidence strongly supports a 12-month surveillance approach rather than immediate colposcopy for non-16/18 HPV-positive, cytology-negative results:

• The 10-year cumulative CIN3+ risk following a negative HPV test is only 0.31%, similar to the 3-year risk after negative cytology (0.30%) 4
• About three-quarters of women with HPV infection and normal cytology clear their infections within 3 years 4
• The risk of CIN3+ within this timeframe is low (1.5%) 4
• HPV testing or co-testing is preferred over cytology alone for follow-up because negative HPV testing is less likely to miss disease 1, 2

Critical Pitfalls to Avoid

• Do not perform immediate colposcopy for women with negative cytology but positive non-16/18 high-risk HPV 2
• Do not use HPV genotyping for further triage in women already confirmed negative for HPV 16/18 2
• Do not perform treatment based on HPV result alone without histologic confirmation of disease 2
• Do not test for low-risk HPV types (e.g., types 6 and 11), as this is not clinically useful 1, 2
• Do not extend screening intervals without appropriate negative HPV test results 3

Long-Term Surveillance Considerations

If high-grade precancer (CIN 2/3) is eventually detected and treated:

• Initial surveillance with HPV test or co-test at 6,18, and 30 months 1, 3
• Long-term surveillance for at least 25 years, even beyond age 65 1, 3, 2
• Testing every 3 years if using HPV testing/co-testing, or annually if using cytology alone 1, 3