Human papillomavirus infection of the fallopian tube as a potential risk factor for epithelial ovarian cancer

Abstract

Human papillomaviruses (HPVs) and herpesviruses are detected in patients with epithelial ovarian cancer (EOC). We sought to analyze the prevalence of HPV's 16 and 18, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA in peripheral blood, ovarian, and fallopian tube (FT) tissue samples collected from 97 EOC patients, including 71 cases of high-grade serous ovarian carcinoma (HGSOC), and from 60 women with other tumors or non-neoplastic gynecological diseases. DNA isolates were analyzed by PCR methods, including droplet digital PCR. The results demonstrate that (1) HPV16 DNA has been detected in one-third of the FT and tumor samples from EOCs; (2) the prevalence and quantity of HPV16 DNA were significantly higher in FT samples from HGSOCs, non-HGSOCs, and ovarian metastases than in those from non-neoplastic diseases; (3) CMV and EBV have been detected in approximately one-seventh of EOC samples. The results suggest that HPV16 might be a potential risk factor for EOC development.

Keywords: Epithelial ovarian cancer; Fallopian tube; Herpesvirus; High-grade serous ovarian carcinoma; Papillomavirus.

Fig. 1

Visualization of nPCR products for HPV16 (a), HPV18 (b), CMV (c), and EBV (d) DNA. Gel image: (1) Positive control (DNA isolated from Ca Ski cells for HPV16, HeLa cells for HPV18, MRC-5 cells infected with CMV AD169 or Davis for CMV, and Namalwa cells for EBV); (2) Cancerous ovarian tissue; (3) Fallopian tube; (4) Peripheral blood; (5) Negative control. Alignment markers (15 bp, 1 kbp).

Fig. 2

Detection of the fragments of the HPV16 E6 (a), HPV18 E7 (b), CMV UL55 (c), and EBV EBNA1 (d) genes by ddPCR in tissue samples collected from patients with epithelial ovarian cancer. A01—positive control; DNA isolated from Ca Ski, HeLa, MCR-5 infected with CMV, and Namalwa cells, respectively. B01, C01, D01—DNA isolated from clinical materials, including fallopian tube, ovarian tumor, and whole blood samples. E01—no-template control (NTC). Channel 1 (Ch1)—positive droplets containing the virus gene amplicon are colored blue, while negative drops are marked in black.

Fig. 3

HPV16 copy numbers in fallopian tube samples from HGSOCs, non-HGSOC cases, patients with ovarian metastases, BOTs, and control group, including benign tumors. The virus copy number was quantified by ddPCR or qPCR. The bars in the scatter plot represent the mean viral load and the whiskers represent the SEM values. The Mann–Whitney U test was used to assess statistically significant differences.