Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models

Abstract

BACKGROUND: In addition to the oncogenic human papillomavirus (HPV), several cofactors are needed in cervical carcinogenesis, but whether the HPV covariates associated with incident (i) CIN1 are different from those of incident (ii) CIN2 and (iii) CIN3 needs further assessment. OBJECTIVES: To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV covariates associated with incident CIN1, CIN2, and CIN3. STUDY DESIGN AND METHODS: HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3187) and LAMS study (n = 12,114), using competing-risks regression models (in panel data) for baseline HR-HPV-positive women (n = 1105), who represent a sub-cohort of all 1865 women prospectively followed-up in these two studies. RESULTS: Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2, and CIN3, respectively. Among these baseline HR-HPV-positive women, the risk profiles of incident CIN1, CIN2 and CIN3 were unique in that completely different HPV covariates were associated with progression to CIN1, CIN2 and CIN3, irrespective which categories (non-progression, CIN1, CIN2, CIN3 or all) were used as competing-risks events in univariate and multivariate models. CONCLUSIONS: These data confirm our previous analysis based on multinomial regression models implicating that distinct covariates of HR-HPV are associated with progression to CIN1, CIN2 and CIN3. This emphasises true biological differences between the three grades of CIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common endpoint, e.g., in HPV vaccine trials.