Abstract
PurposeTo evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities.MethodsWe 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.ResultsCompared 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).Conclusionsp16/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.
Highlights
The rates of cervical cancer have been greatly reduced by organized cytology screening programs in developed countries
Of the 854 referral women, 23 (2.7%, 23/854) women with high grade cervical neoplasia were excluded due to cervical treatment after pathological diagnosis at baseline and 21(2.5%, 21/854) women were excluded for out of contact.737 (91.0%, 737/810) women completed the follow-up, 402 (54.5%, 402/737)women who tested negative for all four screening tests were considered negative for histological diagnosis ; 335(45.5%, 335/737) women tested positive for any of the four tests were referred to colposcopy and 323(96.4%) of 335 referral women completed the colposcopy and biopsy.713 (88.0%, 713/810) with valid baseline and follow-up human papillomavirus (HPV) and p16/ Ki-67 test results were included for analysis. 701(98.3%) of 713 women had valid histological diagnosis in the analysis group
For women aged 25 years and older, the use of cobas HPV Test was approved by FDA for primary cervical cancer screening
Summary
The rates of cervical cancer have been greatly reduced by organized cytology screening programs in developed countries. In China, where efficient screening strategies are lacked, the burden of cervical cancer remains high with an estimation of 98,900 incident cases and 30,500 deaths in 2015[1]. The establishment etiologic association between cervical cancer and human papillomavirus (HPV) [2] drove the renovation of various cervical screening methods, especially high-risk HPV (HR-HPV) DNA testing, which has been evaluated as a replacement of Pap test in primary screening settings[3,4]. At the beginning of young women’s sexual activity, HPV infection is extremely common, but more than 90% of the infections are transient and can be cleared in 1-2 years www.impactjournals.com/oncotarget. HR-HPV positivity N Baseline HR-HPV HR-HPV≠ HPV16/18 HPV 16/18 Follow-up HPV persistence
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