Elevated Expression of Human Papillomavirus-16/18 E6 Oncoprotein Associates with Persistence of Viral Infection: A 3-Year Prospective Study in China

Yu, Lulu; Kang, Lakhwinder Singh; Zhao, Fanghui; Lei, Xiaoqiang; Qin, Yu; Wu, Zeni; Wang, Hong; Chen, Wen; Qiao, You‐Lin

doi:10.1158/1055-9965.epi-15-1057

Cited by 12 publications

(21 citation statements)

References 43 publications

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“…Women within the E6 positive group had a much higher risk of HPV persistence (adjusted OR = 54.64, 95%CI: 7.19–415.09) compared with E6 negative group during the three year follow‐up session. Simultaneously, women who were persistently HPV positive also had a much higher risk of E6 expression (adjusted OR = 360.57, 95%CI: 28.30–4,593.55) . Our study detected a 40.0 (95% CI: 11.8, 135.5) folds higher risk of E6 expression among women with persistent hr‐HPV infection compared with women who only experienced one event of HPV infection during the 15‐year follow‐up period.…”

Section: Discussionsupporting

confidence: 46%

“…These samples were stored within a −80°C freezer and tested after the last visit in the year 2014. The E6 status was determined via the Onco E6 ™ Cervical Test (Arbor Vita Corporation), which is an immunochromatographic lateral flow test that could only detect the HPV 16 and 18 E6 oncoprotein . The test result is determined through visual inspection, with a red colored line indicating presence of the E6 oncoprotein.…”

Section: Methodsmentioning

confidence: 99%

“…8,9 Few studies have been performed so far as a means to verify the potency of the E6 oncoprotein detection to predict a long-term risk of cervical cancer. 10 In this study, we investigated the clinical performance of the HPV 16/18 E6 oncoprotein test (E6), which targets the two main hr-HPV genotypes, as a HPV positivity triage method in detection of CIN31 in a longterm prospective cohort.…”

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confidence: 99%

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Risk stratification and long-term risk prediction of E6 oncoprotein in a prospective screening cohort in China

Zhang

et al. 2017

Int. J. Cancer

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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 (OR = 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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Section: Discussionsupporting

confidence: 46%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Risk stratification and long-term risk prediction of E6 oncoprotein in a prospective screening cohort in China

Zhang

et al. 2017

Int. J. Cancer

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“…Despite limited numbers, our finding of disease in at least half the women who were positive for E6 despite the absence of lesions in the initial assessment are an indicator of the extraordinary specificity and predictive value of the test. In a prospective study also in China, detection of E6 oncoproteins of HPV 16 and 18 was a strong predictor of HPV 16 and 18 persistence, and in another Chinese report E6 detection was also a strong predictor of concurrent and future development of CIN3. The high specificity of the E6 test indicates that it can represent a useful method for triage of women with an HPV positive test, which suffers from limited specificity and positive predictive value.…”

Section: Discussionmentioning

confidence: 90%

Performance of an HPV 16/18 E6 oncoprotein test for detection of cervical precancer and cancer

Ferrera

Valladares

Cabrera

et al. 2019

Intl Journal of Cancer

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HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV‐tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow‐up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18‐related HSIL+ was 96.8% (95%CI = 83.8–99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3–68.6). Specificity was 97.5% (95%CI = 93.7–99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18‐related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.

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“…In our study, the positive rate of OncoE6 for CIN2 and CIN3 was 13.2% and 44.0%, respectively, so we speculate the E6 positive CIN2 or CIN3 may have a higher risk to progress than negative ones, but no prospective studies have been done to directly prove this so far. Meanwhile, studies have clarified that there were a strong association between E6 oncoprotein expression and HPV persistence infection which directly associated with CIN progression and cervical cancer . Although OncoE6 recovered part of cobas 16/18 negative cervical cancer, it still missed a few cancer cases and those misses could be due to false‐negative results.…”

Section: Discussionmentioning

confidence: 99%

Clinical evaluation of human papillomavirus 16/18 oncoprotein test for cervical cancer screening and HPV positive women triage

Jiang

et al. 2018

Intl Journal of Cancer

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HPV-16 and -18 account for about 80% of cervical cancers. We evaluated the performance of HPV-16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid-Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p < 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p < 0.001), but more specific (97.1% vs. 75.4%, p < 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage.

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Elevated Expression of Human Papillomavirus-16/18 E6 Oncoprotein Associates with Persistence of Viral Infection: A 3-Year Prospective Study in China

Cited by 12 publications

References 43 publications

Risk stratification and long-term risk prediction of E6 oncoprotein in a prospective screening cohort in China

Risk stratification and long-term risk prediction of E6 oncoprotein in a prospective screening cohort in China

Performance of an HPV 16/18 E6 oncoprotein test for detection of cervical precancer and cancer

Clinical evaluation of human papillomavirus 16/18 oncoprotein test for cervical cancer screening and HPV positive women triage

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