Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

Background: Although human papillomavirus (HPV) infection has been recognized as the major cause of cervical cancer, only a minority of HPV-infected women develop this malignancy. An increasing amount of evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown. Methods: In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls ( P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed ( P trend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant. Conclusions: Increased mtCN in cervical exfoliated cells is associated with cervical cancer after HPV infection. Our study provides a basis for future studies to determine the potential of mtCN as a novel biomarker in cervical cancer screening.