The association between human papillomavirus 16, 18 DNA load and E6 protein expression in cervical intraepithelial neoplasia and cancer.

It has been reported that high HPV DNA load and elevated E6 protein expression correlate with cervical cancer, but no epidemiological study has been performed. To assess the association between type-specific HPV DNA load and presence of E6 protein in cervical intraepithelial neoplasia and cancer. This study was a cross-sectional multicenter study performed between 2013 and 2017. A total of 1717 women (normal histopathology: n = 916; CIN1: n = 94; CIN2: n = 63; CIN3: n = 130; SCC: n = 474; adenocarcinoma: n = 40) were included. HPV DNA load and presence of E6 protein were detected. DNA load was measured as log copies/10,000 cells. The HPV16/18-E6 positivity rates increased from negative for DNA to the highest load grade. Compared to the HPV16 DNA negatives, women with low (RR = 31.5, 95%CI = 18.9-52.5), medium-low (RR = 133.5, 95%CI = 77.3-230.7), medium-high (RR = 247.9, 95%CI = 134.9-455.6) and high DNA loads (RR = 677.9, 95%CI = 301.6-1523.7) had increasingly higher relative ratios of HPV16-E6 expression. The association of HPV18-E6 with its DNA load was also significant for low (RR = 27.9, 95%CI = 10.4-74.9), medium-low (RR = 89.0, 95%CI = 32.8-241.3), medium-high (RR = 276.8, 95%CI = 76.7-998.9) and high grade (RR = 441.2, 95%CI = 97.7-1992.4). The positivity rates of both HPV16 DNA and E6 protein increased consistently with the severity of diseases from normal histopathology to SCC. Unlike HPV16, the trends of HPV18 DNA and E6 protein fluctuated consistently among women from normal histopathology to cancer. DNA load in E6-positive women was significantly higher than E6-negative for both types. There is a type-dependent association between HPV16/18 DNA load and E6 protein; our study furthers the understanding of the natural history of cervical cancer.

Wu Z ，Yu L ，Lei X ，Qin Y ，Zhang X ，Chen W ，Qiao Y ... -  《-》

Human papillomavirus 16 load and E2/E6 ratio in HPV16-positive women: biomarkers for cervical intraepithelial neoplasia >or=2 in a liquid-based cytology setting?

Boulet GA ，Benoy IH ，Depuydt CE ，Horvath CA ，Aerts M ，Hens N ，Vereecken AJ ，Bogers JJ ... -  《-》

Viral DNA load, physical status and E2/E6 ratio as markers to grade HPV16 positive women for high-grade cervical lesions.

Cricca M ，Morselli-Labate AM ，Venturoli S ，Ambretti S ，Gentilomi GA ，Gallinella G ，Costa S ，Musiani M ，Zerbini M ... -  《GYNECOLOGIC ONCOLOGY》

Human Papillomavirus (HPV) 16/18 E6 Oncoprotein Expression in Infections with Single and Multiple Genotypes.

Factors that differentiate risk of cervical cancer associated with infection with single versus multiple HPV types are yet undefined. We hypothesize that E6 oncoprotein is one determining factor. This cross-sectional, multicenter study was performed between 2013 and 2017. A total of 1,781 women were recruited from six hospitals. Samples were tested for presence of 14 types of high-risk HPV DNA. HPV16/18-positive samples were also tested for HPV16/18-E6 oncoprotein. Of 1,781 subjects, 687 (38.6%) tested positive for HPV16/18. HPV16/18 single infections were associated with higher E6 positivity rates compared with multiple infections only for cancer cases (HPV16: 92.2% vs. 76.5%; HPV18: 93.9% vs. 62.1%) but not for normal histopathology or cervical intraepithelial neoplasia. In HPV16/18 coinfection subjects, the positivity rate was 42.9% for HPV16-E6 and 42.9% for HPV18-E6. The combined positivity rate of either HPV16-E6 or HPV18-E6 among HPV16/18 coinfection subjects was 78.6%, similar with HPV16 (74.8%) and HPV18 (79.5%) single-infection subjects. The positivity rates of HPV16/18 E6 oncoprotein varied depending on the HPV-type composition in multiple infection ("clusters") including HPV types other than 16 and 18. Multiple infection clusters most likely to express HPV16-E6 and HPV18-E6 were HPV16/52 (61.5%) and HPV18/52 (66.7%), and the less were HPV16/45 (10.0%) and HPV18/51 (16.7%), respectively. Patterns of E6 oncoprotein expression varied depending on clustering types. However, expression was greatest in women with single HPV-type infections compared with those with multiple HPV types regardless of histopathology. Our findings provided new insight of natural history of cervical cancer.

Wu Z ，Li TY ，Jiang M ，Yu L ，Zhao J ，Wang H ，Zhang X ，Chen W ，Qiao Y ... -  《-》

Diagnostic value of human papillomavirus (HPV) 16 and HPV18 viral loads for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a cohort of African women living with HIV.

African women living with HIV (WLHIV) are at high risk of cervical cancer but rarely adequately screened. Better strategies enabling identification of WLHIV with high-grade cervical intraepithelial lesions (CIN2+) are required. To investigate the diagnostic value of HPV16 and HPV18 viral loads in a cohort of African WLHIV. HPV16 and HPV18 viral loads were determined by quantitation of the E6 gene DNA by real-time PCR in cervical specimens collected at baseline and endline (16 months) from 245 African WLHIV positive for HPV16 or/and HPV18. Cervical biopsies were graded using the histopathological CIN classification. Women with CIN2+ had higher viral load for HPV16 (p < 0.0001) or HPV18 (p = 0.03) than those without CIN2+. HPV16 viral load ≥3.59 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 93.5% (95%CI: 81.7-98.3%) and 74.1% (95%CI: 66.3-80.6%), respectively, whereas HPV18 viral load ≥1.63 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 59.1% (95%CI: 38.7-76.7%) and 66.9% (95%CI: 58.8-74.1%), respectively. A high baseline HPV16 viral load was significantly associated with persistence of, or progression to CIN2+ at endline; these findings were not observed for HPV18. HPV16 viral load is a powerful marker of CIN2+ in African WLHIV. HPV18 viral load is of lower diagnostic value in this population.

Segondy M ，Ngou J ，Kelly H ，Omar T ，Goumbri-Lompo O ，Doutre S ，Mayaud P ，Didelot MN ... -  《-》