p16/Ki-67 co-expression associates high risk human papillomavirus persistence and cervical histopathology: a 3-year cohort study in China.
p16/Ki-67 co-expression associates high risk human papillomavirus persistence and cervical histopathology: a 3-year cohort study in China.
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p16/Ki-67 共表达与高危人乳头瘤病毒持久性和宫颈组织病理学相关：中国的一项为期 3 年的队列研究
DOI：
10.18632/oncotarget.11705
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发表时间：
2016-10-04
期刊：
影响因子：
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通讯作者：
Chen W
中科院分区：
文献类型：
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作者：
Yu LL;Guo HQ;Lei XQ;Qin Y;Wu ZN;Kang LN;Zhang X;Qiao YL;Chen W
探讨p16/Ki-67共表达与高危人乳头瘤病毒(HR-HPV)感染和宫颈病变的相关性。我们进行了一项为期3年的队列研究，其中2498名年龄在25岁至65岁的中国女性在2011年进行了不同的HPV检测。690名检测呈阳性的妇女和164名全部阴性的妇女接受阴道镜检查，在阴道镜检查前收集宫颈标本进行眼镜蛇HPV检测(罗氏诊断)，其中737例宫颈标本于2014年进行了眼镜蛇、液基细胞学、HPVE6检测(Arbor Vita Corporation)和p16/Ki-67双重染色(罗氏诊断)。对有任何异常结果的妇女进行了阴道镜检查和活检。与无HR-HPV持续感染的妇女相比，HR-HPV持续感染组妇女p16/Ki-67阳性的风险更高，调整后的优势比(OR)和95%可信区间(CI)为6.29(4.07~9.72)；此外，HPV16/18持续感染的妇女的调整优势比其他12个HR-HPV持续感染的妇女高近4倍(调整后OR=17.15，95%CI：7.11~41.33 vs调整OR=4.68，95%CI：2.89~7.58)。此外，p16/Ki-67阳性率随细胞学和组织学异常程度的加重而显著升高，并与CIN2+诊断密切相关(OR=16.03，95%CI：4.46~57.59)。P16/Ki-67共同表达与HR-HPV持续存在密切相关，尤其与HPV16/18和CIN2+病变的存在密切相关。因此，p16/Ki-67可以被认为是宫颈癌筛查的一个合适的生物标志物，特别是在基于HPV的筛查程序中。
To evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities. We performed a 3-year cohort study among which 2498 Chinese women aged 25 to 65 years were screened by different HPV tests in 2011. 690 women who were positive at any of the tests and a random sample of 164 women with all negative results received colposcopy, cervical specimens for cobas HPV test (Roche diagnostics) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas, Liquid-based cytology, HPV E6 test (Arbor Vita Corporation) and p16/Ki-67 dual staining (Roche diagnostics) in 2014. Colposcopy and biopsies was performed on women with any abnormal result. Compared to women without HR-HPV persistent infection, women in the HR-HPV persistence group had a higher risk of p16/Ki-67 positive, with an adjusted Odds Ratio(OR) and 95% confidence interval (CI) of 6.29 (4.07-9.72); moreover, adjusted odds ratio for women who had HPV16/18 persistent infection was nearly 4-folder higher than women with other 12 HR-HPV persistent infection (adjusted OR = 17.15, 95% CI: 7.11-41.33 vs adjusted OR = 4.68, 95% CI: 2.89-7.58). Additionally, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities, and resulted strongly associated with a CIN2+ diagnosis (OR = 16.03, 95% CI: 4.46-57.59). p16/Ki-67 co-expressions associated strongly with HR-HPV persistence, especially with HPV16/18, and the presence of a CIN2+ lesion. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.