Association of estradiol and HPV/HPV16 infection with the occurrence of cervical squamous cell carcinoma

Abstract

The associations between human papillomavirus (HPV) infection or hormonal exposure and cervical cancer risk are well established. However, to the best of our knowledge, the association between high endogenous estradiol levels in conjunction with HPV/HPV16 infection and the risk of cervical squamous cell carcinoma remains unknown. To investigate this, the current study conducted a matched case-control study in Shanxi Province, China, in which clinical samples were obtained from 74 females with newly diagnosed uterine cervix squamous cell carcinoma and 74 matched healthy females who were selected from 582 healthy females according to age, place of residence, marital status and menopausal status. From all participants, DNA was extracted from cells obtained from a cervical smear and serum was separated from venous blood withdrawn during days 5-8 of the menstrual cycle. HPV/HPV16 DNA and estradiol expression levels in the serum were measured by general polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Significant differences were identified in the positive HPV and HPV16 DNA expression rates between patients and controls, with odds ratios (95% confidence interval) of 3.74 (1.84-7.59) and 4.04 (1.97-8.28), respectively. Expression levels of estradiol in patients were significantly higher compared with the controls (P<0.001), however, this was only identified when the HPV16 E2 or E6 oncogene status was negative. Considering 40 ng/ml as the cutoff estradiol level, 78.38% of patients exhibited high estradiol levels, which was significantly higher than the percentage of controls (P<0.001). An additive interaction pattern was revealed between estradiol expression levels and HPV/HPV16 infection. The results suggest that among the various types of HPV, HPV16 may be most likely to cause uterine cervix squamous cell carcinoma and an abnormally high level of endogenous estradiol may further increase this risk. Therefore, estradiol therapy may represent a new treatment strategy for cases of cervical cancer associated with HPV infection.

Significance of HPV16 Viral Load Testing in Anal Cancer

“…Epidemiological studies have shown that oral contraceptives and multiple pregnancies are risk factors for cervical cancer [24]. Further, HPV-positive women with high estradiol levels had higher risk of cervical cancer than women who were only either HPV-positive or exhibited high levels of estradiol [25]. These results confirm the additive effect of estradiol and HPV infection found in experimental studies.…”

A Novel Model for Papillomavirus-Mediated Anal Disease and Cancer Using the Mouse Papillomavirus

“…One possible explanation for the enhanced susceptibility of the cervix to persistent infection compared to the anus is the role of endogenous estrogen. Estrogen has been shown to play a key role in potentiating the development of cervical cancer, and clinical evidence suggests that higher estrogen levels are associated with increased persistence of high-risk HPVs ( 54 , 55 ). Furthermore, we have shown that MmuPV1 infection persists in 100% of mice treated with exogenous estrogen and that estrogen-treated mice developed more severe disease ( 33 ).…”

Mining of prognosis-related genes in cervical squamous cell carcinoma immune microenvironment

“…It is widely accepted that HPV infection has a significant association with the occurrence and progression of CSCC ( Ding et al, 2019 ). Therefore, we separately analyzed the ImmuneScore, StromalScore and ESTIMATEScore distribution among CSCC patients with or without HPV infection.…”