Risk of high-grade precancerous lesions and invasive cancers in high-risk HPV-positive women with normal cervix or CIN 1 at baseline-A population-based cohort study

Infection with high-risk human papillomavirus (HR-HPV) is transient and clears on its own in majority of the women. Only a few women who have persistent infection may finally develop cervical intraepithelial neoplasia (CIN) or cervical cancer in later years. The risk of progression in the HR-HPV-positive women with normal cervix or low-grade lesion on colposcopy and histopathology at baseline is less studied. We performed a longitudinal study on 650 HR-HPV-positive women with colposcopy and/or histopathology-proved normal or CIN1 diagnosis at baseline to assess the cumulative risk of development of high-grade CIN. After a mean follow-up of 2.1 person years of observation (PYO) (range 0.1-5.1), the cumulative incidence of CIN21 (6.4%; 3.0/100 PYO) was significantly higher in women who had persistent HR-HPV infection compared to those who cleared the infection (adjusted HR 6.28; 95% CI 2.87-13.73). The risk of viral persistence in women aged 50-60 years was two times higher compared to women aged 40-49 years and three times higher compared to women aged 30-39 years. The probability of having persistent infection increased progressively with higher viral load at baseline (adjusted HR 3.29, 95% CI 2.21-4.90 for RLU >= 100; adjusted HR 2.69, 95% CI 1.71-4.22 for RLU 10-100). Women with increasing viral load at follow-up had four times higher risk of developing CIN2 or worse lesions as compared to those with decreasing load (20.9% vs 4.8%; p < 0.001). In the context of developing countries where cytology or genotyping triaging is not feasible, colposcopy referral of HR-HPV-positive women with advancing age, viral persistence, and increasing viral load may be considered.