Is colposcopy still necessary if a patient is Human Papillomavirus (HPV) positive but has negative cytology for intraepithelial lesion or malignancy?

Management of HPV-Positive, Cytology-Negative Results

For women aged 30 and older who test positive for HPV but have negative cytology (NILM), repeat HPV and cytology testing at 12 months is the preferred management strategy, with colposcopy reserved for those who remain HPV-positive or develop abnormal cytology on repeat testing. 1

Initial Management Algorithm

Standard Approach for Non-HPV 16/18 Types

• Repeat co-testing at 12 months is the preferred management for women ≥30 years with HPV-positive, cytology-negative results 1
• If HPV remains positive at 12 months, colposcopy is recommended regardless of cytology results 1
• If repeat cytology shows any abnormality (≥ASC-US), manage according to the cytology result with appropriate colposcopy referral 1
• If both HPV and cytology are negative at 12 months, return to routine screening 1

Special Consideration for HPV 16 or 18

• Immediate colposcopy is recommended for all women with HPV 16 or 18 positive results, even with normal cytology, due to the high cancer risk 2, 3
• For HPV 18 specifically, endocervical sampling at colposcopy is acceptable due to its association with adenocarcinoma 2
• The 3-year risk of CIN3+ for HPV 16-positive women with negative cytology is 10.6%, which exceeds the threshold for immediate colposcopy 4
• HPV 33 and HPV 18 confer intermediate risks of approximately 5.9% for CIN3+ 4

Risk Stratification

Why Not Immediate Colposcopy for All?

• The overall 3-year cumulative risk of CIN3+ among HPV-positive, cytology-negative women is 4.6% 4
• For HPV-positive women who are HPV 16-negative, the risk drops to only 2.4% 4
• The negative predictive value of HPV testing is 90% sensitive for detecting precancer, with less than 0.15% risk over 5 years following a negative test 3
• Among HPV-negative cases with unsatisfactory cytology, the HSIL rate is only 0.4% compared to 5.7% in HPV-positive cases 5

Clinical Implications

• Current precancer risk of less than 4% warrants surveillance rather than immediate colposcopy 3
• The risk-based approach balances detection of disease against overtreatment and associated harms, including preterm labor risk from excisional procedures 3

Common Pitfalls and Caveats

Do Not Skip Colposcopy If:

• HPV 16 or 18 is detected - these require immediate colposcopy regardless of cytology 2
• Repeat testing at 12 months shows persistent HPV positivity - this indicates failure to clear infection and warrants colposcopy 1
• Any cytologic abnormality develops during follow-up 1

Important Considerations

• One study found that all cases of HSIL in HPV-positive, cytology-negative women were diagnosed after the second HPV test, suggesting the importance of repeat testing 6
• For postmenopausal women with LSIL cytology and negative HPV, the risk of CIN2+ is minimal, supporting conservative management 7
• HPV testing should only target high-risk oncogenic types (16,18,31,33,35,39,45,51,52,56,58,59,68) - testing for low-risk types is unacceptable 1

Follow-Up Protocol

• First repeat test at 12 months with both HPV and cytology 1
• If negative at 12 months, return to routine age-based screening 1
• If positive at 12 months, proceed to colposcopy 1
• Long-term surveillance should continue for at least 25 years after any treatment for high-grade precancer 2