Long-term oral contraceptive use as a risk factor for high-grade cervical lesions in women with high-risk human papillomavirus: a retrospective cohort analysis.

Objective: While high-risk human papillomavirus (HPV) is the established cause of cervical intraepithelial neoplasia (CIN), cofactors influencing progression to high-grade disease remain poorly defined. This study aimed to investigate the association between long-term oral contraceptive use and the risk of high-grade CIN (grade 2/3) in a high-risk referral population.

Methods: A retrospective analysis was conducted on the records of 684 women screened at a specialized gynecologic oncology clinic (2019-2024). Data on oral contraceptive use (≥5 years), high-risk HPV status, age, and smoking history were extracted. The primary outcome was CIN grade. To mitigate bias from sparse data, Firth-penalized logistic regression was used to calculate adjusted ORs (aOR) for the association between long-term oral contraceptive use and CIN grade.

Results: Long-term oral contraceptive use was reported by 5.6% of the cohort. After adjusting for confounders, long-term oral contraceptive use was strongly associated with a 16.8-fold increased odds of high-grade CIN (aOR 16.79, 95% CI 3.82 to 73.70, p < .001). However, the wide CI indicates significant statistical uncertainty in the magnitude of the effect. Conversely, oral contraceptive use was associated with significantly lower odds of low-grade CIN (aOR 0.04, 95% CI 0.01 to 0.15, p < .001).

Conclusions: In this high-risk population, long-term oral contraceptive use is a significant independent risk factor for high-grade cervical lesions, while paradoxically being associated with a lower risk of low-grade disease. This suggests an important role for hormonal factors in the progression of cervical neoplasia. Clinicians should consider long-term oral contraceptive use a key risk indicator in HPV-positive women and incorporate this modifiable factor into patient counseling.