Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Cancer Med. 2019 Aug;8(10):4845-4851. doi: 10.1002/cam4.2246. Epub 2019 Jun 26.
Although high-risk human papillomavirus (HR-HPV) infection is recognized as the main cause of cervical cancer, only a minority of HPV-infected women develop this malignancy. Increasing evidence suggests that alterations of telomere length might be implicated in carcinogenesis. However, the association between cervical cancer and telomere length remains unknown.
This case-control study included 591 cervical cancer patients and 373 cancer-free controls, all of whom were infected with HR-HPV. Relative telomere length (RTL) in cervical cancer exfoliated cells was measured by quantitative PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis.
HPV16, 18, 52, and 58 were common in both case and control groups. The proportion of HPV16 infection tended to increase across the quartiles of RTL (P < 0.001). There was no statistically significant association of RTL with tumor differentiation, histological type, and FIGO stage. After adjustment for age and HPV types, the lowest quartile of RTL presented a 49% lower risk (OR = 0.51, 95% CI: 0.35, 0.76; P < 0.001) than those with the highest quartile of RTL. There was also a dose-response relationship of shorter RTL on lower risk of cervical cancer (P < 0.001).
Shortened telomere length in cervical exfoliated cells was related to the lower risk of cervical cancer among HR-HPV-positive women, which might help to improve cervical cancer screening and surveillance. Further prospective studies with large sample should be designed to validate our preliminary findings, and evaluate the potential efficacy of telomere length for cervical cancer screening.
尽管高危型人乳头瘤病毒(HR-HPV)感染被认为是宫颈癌的主要病因,但仅有少数 HPV 感染女性会发展为这种恶性肿瘤。越来越多的证据表明,端粒长度的改变可能与肿瘤发生有关。然而,宫颈癌与端粒长度之间的关联尚不清楚。
本病例对照研究纳入了 591 例宫颈癌患者和 373 例无癌对照者,所有研究对象均感染 HR-HPV。采用实时定量 PCR 检测宫颈脱落细胞中的相对端粒长度(RTL)。采用 logistic 回归分析计算比值比(OR)及其 95%置信区间(CI)。
HPV16、18、52 和 58 在病例组和对照组中均较为常见。随着 RTL 四分位间距的增加,HPV16 感染的比例也呈上升趋势(P<0.001)。RTL 与肿瘤分化程度、组织学类型和 FIGO 分期均无统计学关联。在校正年龄和 HPV 类型后,RTL 最低四分位间距者发生宫颈癌的风险较 RTL 最高四分位间距者降低 49%(OR=0.51,95% CI:0.35,0.76;P<0.001)。RTL 越短,宫颈癌的发病风险越低,两者之间存在剂量-反应关系(P<0.001)。
HR-HPV 阳性女性宫颈脱落细胞中的端粒缩短与宫颈癌风险降低相关,这可能有助于改善宫颈癌筛查和监测。需要设计进一步的大样本前瞻性研究来验证我们的初步发现,并评估端粒长度用于宫颈癌筛查的潜在效果。