Risk stratification and long‐term risk prediction of E6 oncoprotein in a prospective screening cohort in China |
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Authors: | Qian Zhang Li Dong Shangying Hu Ruimei Feng Xun Zhang Qinjing Pan Junfei Ma Li Zhang Xuelian Zhao Rengaswamy Sankaranarayanan Youlin Qiao Fanghui Zhao |
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Institution: | 1. Department of Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;2. Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;3. Department of Epidemiology, Xiangyuan Women and Children's Hospital, Changzhi, Shanxi Province, China;4. Screening Group, Section of Early Detection and Prevention, International Agency for Research on Cancer, Lyon, France |
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Abstract: | E6 oncoprotein is a necessary agent of HPV driven oncogenic transformation. This study is aimed at evaluating the risk stratification potency of HPV 16/18 E6 oncoprotein (E6) as a triage method for HPV positivity. Moreover, it also acts as a predictor of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The screening cohort of 1,997 women was followed for a 15 year period in approximate five‐year intervals. Participants were concurrently screened by HPV DNA testing (HC2), liquid based cytology (LBC), visual inspection with acetic acid (VIA) and were referred to colposcopy and biopsy if any tests reflected positive. E6 was performed on cervical samples collected from this cohort in 2005 and 2014. The ability of E6 to predict CIN3+ risk after the five‐ and ten‐year interval was evaluated. Among HPV positive women in 2005, E6 indicated the lowest positive rate (9.9%) compared to LBC (48.4%) and VIA (28.0%), however, a higher prevalence rate (10.3%) and 10‐year cumulative incidence rate (53.0%) of CIN3+ were detected among women who were E6 positive. Meanwhile, only 4.2% and 2.9% of women with abnormal LBC and positive VIA were diagnosed as prevalent CIN3+ in 2005, 23.0% and 16.5% developed to CIN3+ after year 10, respectively. Strong associations were found between precedent and subsequent HPV persistence and E6 oncoprotein expression (ORadjusted = 40.0 and 21.2, respectively). E6 oncoprotein could serve as a low‐cost, highly specific, strongly indicative point‐of‐care method in the triage and treatment of HPV positive women. |
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Keywords: | HPV E6 oncoprotein risk predictor triage screening cohort cervical cancer |
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