Research On E6Protein And DNA Test Of HPV16/18/45as A Primary Screening Or Triage Test In Cervical Cancer Screening In Low Resource Settings

Objectives:To evaluate the clinical performance of two easy-to-conduct, rapid and low cost molecular screening tests(AV Avantage HPV E6test and careHPV16/18/45) as a primary screening and/or triage test among the HPV positives for the detection of prevalent CIN2+on a population based screening study. Thus to explore the possible and appropriate cervical cancer screening strategies in low resource settings. And to assess the impact of one time group education on the change of women's knowledge about HPV and cervical cancer as well as attitudes towards HPV vaccination.Material and Methods:Two high risk communities (Baisang Xiang and Dingdian Town) were targeted depending on the proposed sample size from Shanxi. Then22villages under the communities were randomly selected from a total number of38.Non-pregnant women aged25-65, with no history of CIN or cervical cancer, or hysterectomy and who were mentally and physically competent to provide written, informed consent from the chosen village, were eligible for enrolment. A group of women from the enrolled screening population were randomly selected and were invited to a interviewer-administrated questionnaire titled "Knowledge and Attitudes About Human Papillomavirus (HPV) and HPV vaccine" both before and after a group education.HC2(self sampling and doctor sampling),careHPV(self sampling and doctor sampling),Avantage HPV E6test (doctor sampling) and VIA were conducted as the primary screening tests at the enrollment visit. careHPV16/18/45was tested among samples tested positive for careHPV as a triage. All women screened positive by any of the primary screening tests and a10%random sample of the women who tested negative by all of those tests were invited to return on a separate day for a second VIA and colposcopy. The colposcopist was blinded to the screening results. Any visible lesion under colposcopy was directly biopsied. If no apparent colposcopic abnormality was found, the colposcopist was then unmasked to the screening results.A random biopsy at 2,4,8,10o'clock at the squamo-columnar junction was taken if any of the screening result was positive. An endocervical curettage (ECC) was done on women with unsatisfactory colposcopy examination. Women who screen negative and were without any colposcopic indications of abnormality did not undergo colposcopically-directed biopsies. Women with pathology confirmed CIN2or worse were treated accordingly by standard procedures.A pre-designed scale called "Knowledge and Attitudes about Human Papillomavirus (HPV) and HPV vaccine" was administrated to a random sample from the enrolled screening population by trained interviewers both before and after a group education. Before the group education, simple questions on the awareness of HPV and cervical cancer and attitudes towards HPV vaccines were asked to understand the baseline information. After the group education, more specific knowledge about HPV and cervical cancer screening were asked. Attitudes towards vaccines were also examined.Results:1. The high risk HPV prevalence in the target population was15.1%and it peaked among women younger than30and older than40years of age. The percentage positivity of E6protein of three high risk HPV types (HPV16/18/45) was1.6%. Using AV Avantage HPV E6test as a primary screening method produces the sensitivity of44.4%and specificity of99.2%. Compared with HPV DNA testing, HPV E6test is less sensitive but more specific and provides a PPV of50.0%. Compared with VIA from this study, HPV E6test provides both better sensitivity and specificity.2. If HPV E6test alone was used as a triage, the percentage of women in need immediate colposcopy decreased from14.0%to2.0%, with a sensitivity, specificity and PPV for CIN2+of42.6%,99.4%and54.8%. By comparison, testing for the HPV DNA of HPV16,18, and45using careHPV16/18/45was more sensitive (63.0%) but less specific (97.9%) than testing for E6of the same HPV genotypes. Combined use of high viral load and careHPV16/18/45(high viral load and/or careHPV16/18/45+) could produce a sensitivity of72.2%as well as guarantee a relative high specificity (96.1%) and PPV (24.4%).3. Group education as an intervention could greatly improve the awareness of HPV and cervical cancer of the target population (P<0.001) and their attitudes towards HPV vaccines (P<0.001). Before the group education, awareness of HPV and cervical cancer were5.9%(54/913)and63.0%(575/913), respectively, and it increased to be59.0%(539/913)and89.3%(815/913), respectively,after the group education. Intervention increased women's willingness to vaccinate their daughters by5%and7%to vaccinate themselves.Conclusion:The high prevalence and two peaks of HPV infection pose great challenge on cervical cancer prevention in China. As a primary screening method, AV Avantage HPV E6test is specific but less sensitive. Future efforts should focus on decreasing the cut-off value of E6positivity and expanding the number of targeted HPV genotypes for pan-HPV coverage to improve the performance. Currently, HPV E6test is possible to be an alternative screening method in low resource settings where HPV DNA testing is not available and experienced doctors to conduct VIA are not presented.Primary careHPV screening with careHPV16/18/45alone or combined with high viral load triage is sensitive and more specific than HPV DNA screening with no triage and decrease colposcopy referrals. It appears to be a feasible cervical cancer screening strategy in low resource settings.One time group education by local health professionals improves the awareness of HPV and cervical cancer among the target women. It also increases women's acceptability of HPV vaccines both for their daughters and for themselves. Group education is a feasible and effective intervention to raise awareness of cervical cancer and its prevention in low resource settings.