Human Papillomavirus Cofactors by Disease Progression and Human Papillomavirus Types in the Study to Understand Cervical Cancer Early Endpoints and Determinants

Human papillomavirus (HPV) cofactors for cervical cancer include smoking, multiparity, and oral contraceptive use, but their mechanisms of action are not fully understood. It is also unknown whether cofactors vary by HPV genotypes. The Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) is a cross-sectional study comprising women referred to the University of Oklahoma from November 2003 to September 2007 for abnormal cervical screening results. Detailed questionnaire data and liquid cytology specimens were collected and the latter was genotyped for HPV using the LINEAR ARRAY HPV Genotyping Test. The present analysis includes women with both questionnaire and HPV data and diagnosed with <CIN1 (n = 535), CIN1 (n = 497), CIN2 (n = 336), CIN3 (n = 292), and cancer (n = 80). We evaluated HPV types and cofactors among HPV-infected women by calculating odds ratios (OR) and 95% confidence intervals (95% CI) for CIN3 and CIN2 separately compared with <CIN2 using a polytomous logistic regression model; cancers were excluded from further analysis due to the substantially higher ages of these women. We found that HPV-infected women with minor histologic or cytologic abnormalities (e.g., CIN1, ASCUS, and LSIL) were indistinguishable from those with normal histology/cytology and were thus combined to form the referent group (<CIN2). Among women positive for oncogenic HPV, current smokers had a 2.5-fold increased risk for CIN3 (95% CI, 1.8-3.6) compared with nonsmokers. Among HPV16-infected women, current smokers had elevated risk for both CIN2 (OR, 1.9; 95% CI, 1.1-3.2) and CIN3 (OR, 2.7; 95% CI, 1.6-4.6). Our data suggest that non-HPV16-related CIN2 likely reflects a combination of CIN1 and CIN3 diagnosis, whereas HPV16-related CIN2 may indicate a precancerous state. Investigations on the molecular distinctions along the disease continuum of cervical pathogenesis by HPV type are needed.