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

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background </jats:bold>Although human papillomavirus (HPV) infection has been recognized as the cause of cervical cancer in over 99% of cases, only a minority of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown.<jats:bold>Methods </jats:bold>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). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models.<jats:bold>Results </jats:bold>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 (1.63 <jats:italic>vs.</jats:italic> 1.23, <jats:italic>P </jats:italic>= 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; <jats:italic>P </jats:italic>&lt; 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (<jats:italic>P</jats:italic><jats:sub>trend </jats:sub>&lt; 0.001). The interaction between mtCN and HPV types was statistically nonsignificant.<jats:bold>Conclusions </jats:bold>In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.</jats:p>