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

Abstract

Objective Co-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. Methods The 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. Results Long-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]; 2.233 [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) comparing cancer to CIN3. Conclusions Differences 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.

Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling

“…Prior clinical, epidemiological, and animal model results suggest that estrogen and ERα are critical to CxCa development and maintenance (16,20,21). Consistent with this, 217 of 1,115 genes previously characterized as estrogen-responsive in breast tissue [Dataset S9 (32)] showed strong differential expression across the cervical samples analyzed here.…”

“…These and other results indicate that in high-grade cervical lesions and CxCa, estrogen signaling must largely proceed indirectly through activated fibroblasts in the stromal microenvironment. These findings reveal major differences in the possible tumor-promoting effects of estrogen in CxCa and breast cancer, with corresponding clinical implications (16,20,21).…”

“…Many established cervical cancer risk factors, such as young age at onset of sexual activity and a high number of sexual partners, are related to exposure to HPV. Risk factors that are associated with progression from HPV infection to precancer include smoking and oral contraceptive use (15,16). The exact role of hormonal factors in progression to precancer and cancer is unclear.…”

Fatores associados às alterações cérvico-uterinas de mulheres atendidas em um município polo do oeste catarinense Factors associated to uterine-cervix changes in women assisted in a pole town in western Santa Catarina

“…8 As regards the use of contraceptive pill, it was observed that its use resulted in almost twice the chances of having epithelial cellular changes, similar to the one found in another study, in which the risk of lesions was 2.42 times in the women that used it for more than 10 years. 33 However, other researches did not show a significant association between the oral contraceptive use and the presence of cellular changes. 34 The oral contraceptives alone have no effect on the progression or development of cervical lesions, but they can act in synergy, increasing the susceptibility to develop highdegree lesions in women infected with HPV.…”

Selected Risk Factors for Cervical Cancer and Barriers to Cervical Cancer Screening

“…Higher number of sexual partners (more than 4) proved to be the most important risk factor. Another studies confirmed that the risk of HPV infection persistence, the development of CIN lesions, and cervical cancer increase with the number of sexual partners (10). Early onset of sexual activity, i.e.…”