Ding Ling, Liu Chunliang, Zhou Qin, Feng Meijuan, Wang Jintao
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Oncol Lett. 2019 Mar;17(3):3548-3554. doi: 10.3892/ol.2019.10005. Epub 2019 Feb 1.
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all participants, DNA was extracted from cells obtained from a cervical smear and serum was separated from venous blood withdrawn during days 5-8 of the menstrual cycle.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 cut-off 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.
人乳头瘤病毒（HPV）感染或激素暴露与宫颈癌风险之间的关联已得到充分证实。然而，据我们所知，高内源性雌二醇水平与HPV/HPV16感染联合存在时与宫颈鳞状细胞癌风险之间的关联仍不清楚。为了对此进行研究，本项研究在中国山西省开展了一项匹配病例对照研究，从74例新诊断为子宫颈鳞状细胞癌的女性患者以及从582名健康女性中根据年龄、居住地、婚姻状况和绝经状态选取的74名匹配的健康女性中获取临床样本。从所有参与者中，从宫颈涂片获得的细胞中提取DNA，并从月经周期第5 - 8天抽取的静脉血中分离血清。分别通过普通聚合酶链反应和酶联免疫吸附测定法检测血清中的HPV/HPV16 DNA和雌二醇表达水平。患者与对照组之间的HPV和HPV16 DNA阳性表达率存在显著差异，优势比（95%置信区间）分别为3.74（1.84 - 7.59）和4.04（1.97 - 8.28）。患者的雌二醇表达水平显著高于对照组（P<0.001），然而，这仅在HPV16 E2或E6癌基因状态为阴性时才被发现。以40 ng/ml作为雌二醇水平的临界值，78.38%的患者表现出高雌二醇水平，这显著高于对照组的百分比（P<0.001）。雌二醇表达水平与HPV/HPV16感染之间呈现出相加交互作用模式。结果表明，在各种类型的HPV中，HPV16可能最有可能导致子宫颈鳞状细胞癌，而内源性雌二醇水平异常升高可能会进一步增加这种风险。因此，雌二醇治疗可能代表了一种针对与HPV感染相关的宫颈癌病例的新治疗策略。
