The role of co-factors in the progression from human papillomavirus infection to cervical cancer

ObjectiveCo-factors for cervical cancer, including oral contraceptive (OC) use, smoking and multiparity have been identified; however, the stage at which they act in cervical carcinogenesis is not clear. We compared established risk factors among women with CIN2 and CIN3 to evaluate the heterogeneity of these factors in precancer and also assessed their role during cervical carcinogenesis.MethodsThe current analysis included 2783 women with various stages of cervical disease who were enrolled in the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) and the Biopsy Study. Associations of co-factors within cervical precancer and at different stages of cervical carcinogenesis were estimated using logistic regression.ResultsLong-term OC use (10 + years vs. never: OR = 2.42, 95% CI: [1.13–5.15]), multiparity (3 + births vs. nulliparous: OR = 1.54 [1.04–2.28]), smoking (ever vs. never: OR = 1.95 [1.48–2.58]), and no Pap test in the previous five years (2.05 [1.32–3.17]) were positively associated with CIN3 compared to CIN2. We observed that long-term OC use, parity and smoking were associated with an increased risk of CIN3 compared to < CIN2 (1.97 [1.12–3.46]; 2.23 [1.59–3.11]; 2.60 [2.04–3.30], respectively), whereas associations were not significantly different (OC use, parity) or showed decreased risk (smoking) when comparing cancer to CIN3.ConclusionsDifferences in established risk factors suggest that CIN3 is a more specific definition of precancer than CIN2. Hormonally-related factors and smoking play a role in the transition from human papillomavirus infection to precancer.

► CIN2 and CIN3 are heterogeneous with respect to known cervical cancer risk factors.
► Hormonal factors are important for the progression from HPV infection to precancer.
► Smoking promotes progression from HPV infection to precancer.