In a woman aged 25 years or older with high‑grade squamous intra‑epithelial lesion or CIN 2‑3, does a negative HPV test eliminate the need for colposcopy and treatment?

HPV-Negative HSIL/CIN 2-3: Does It Eliminate Need for Colposcopy?

No, a negative HPV test does NOT eliminate the need for colposcopy and treatment in women aged ≥25 years with high-grade squamous intraepithelial lesion (HSIL) or CIN 2-3. Colposcopy with histological confirmation remains mandatory regardless of HPV status, though a negative HPV test provides reassurance about the absence of high-grade disease and may influence subsequent management decisions. 1, 2

Primary Management Algorithm

Initial Evaluation (HSIL Cytology)

• Immediate colposcopy with endocervical assessment is recommended for all women with HSIL cytology, regardless of HPV test results. 1 The prevalence of CIN 2-3 in women with HSIL cytology is approximately 50%, making colposcopy non-negotiable. 1

• Alternative option: An immediate diagnostic excisional procedure may be considered, especially for women at risk of non-compliance or those who have completed childbearing. 1

• HPV testing does not alter management: Although HPV testing for HSIL is not formally included in guidelines, a negative test provides reassurance but does not eliminate the need for colposcopic evaluation. 1

Histologically Confirmed CIN 2-3

For Women Aged ≥25 Years

• Treatment is the standard approach: Either ablation or diagnostic excision is acceptable when colposcopy is satisfactory. 1

• Active surveillance may be considered in carefully selected patients who meet ALL of the following criteria: 1

  • Willing and likely to comply with intensive monitoring every 6 months
  • Squamocolumnar junction and upper lesion limit fully visible
  • No immunosuppression
  • No previous cervical treatment
  • Multidisciplinary team review of cytology, colposcopy, and biopsy

• Risk stratification for active surveillance: 1

  • Higher progression risk (favor treatment): HPV 16/18 positive, HSIL cytology, large lesion size (>2 quadrants), expansile CIN, significant crypt involvement
  • Lower progression risk (may consider surveillance): Other high-risk HPV types with ASC-US/LSIL cytology, normal cytology with non-16/18 HPV

Role of HPV Testing in CIN 2-3 Management

Post-treatment surveillance: HPV testing has superior negative predictive value (98%) compared to negative resection margins (91%) or cytology alone (93%) for detecting residual/recurrent disease. 1 Women who remain HPV-positive after treatment have significantly increased risk of recurrence. 1

Active surveillance protocol (if chosen): 1

• Co-testing or HPV testing with reflex cytology every 6 months
• Histological biopsy every 6 months if persistent/progressive disease suspected
• Continue until HPV-negative or decision to treat is made

Evidence Quality and Nuances

Strength of Recommendations

The 2025 British Society of Colposcopy and Cervical Pathology/European Society of Gynaecologic Oncology consensus statement 1 represents the most recent high-quality guideline, acknowledging that active surveillance is acceptable for selected CIN 2 patients aged ≥25 years, with no upper age limit if criteria are met.

However, the 2009 ASCCP guidelines 1 emphasize that observation of CIN 2-3 in non-adolescent, non-pregnant women is generally unacceptable, with treatment being the standard of care.

Research Evidence on HPV-Negative HSIL

A 2015 Korean multicenter study 3 found that only 8.8% of women with ASC-H (a less severe abnormality than HSIL) who were HPV-negative had CIN 2+ lesions, with no cases of invasive cancer. This suggests HPV-negative status substantially reduces risk, but this study examined ASC-H, not confirmed HSIL cytology or histological CIN 2-3.

A 2015 Japanese study 4 demonstrated that among women with HSIL/ASC-H cytology, even those testing negative for eight high-risk HPV types still had >35% risk of CIN 3+, warranting immediate colposcopy.

Critical Pitfalls to Avoid

• Do not defer colposcopy based solely on negative HPV testing in women with HSIL cytology—the cytological diagnosis itself mandates evaluation. 1

• Do not assume HPV-negative status eliminates cancer risk in women aged ≥25 years with confirmed CIN 2-3—approximately 12% of CIN 3 progresses to invasive cancer without treatment. 1

• Do not offer active surveillance to immunosuppressed women or those with previous cervical treatment—these patients require definitive treatment. 1

• Do not confuse management of adolescents/young women (<25 years) with older women—conservative management is preferred in younger women due to high regression rates (60-90%), but this does not apply to women ≥25 years. 1, 5

• Ensure adequate colposcopy: If the squamocolumnar junction is not fully visible or colposcopy is unsatisfactory, diagnostic excision is recommended rather than observation. 1

Age-Specific Considerations

Women aged 25-40 years with CIN 2: A 2025 study 6 found 24.9% had occult CIN 3+ in excision specimens, with HPV 16/18 (OR 2.61) and HSIL cytology (OR 4.14) as independent risk factors. This supports treatment for most women in this age group, particularly those with these high-risk features.

Reproductive counseling: Women should be informed that preterm birth risk is lower if lesions regress spontaneously but higher if progression occurs and treatment is performed later. 1