Cervical cancer prevention among long-term screening non-attendees by vaginal self-collected samples for hr-HPV mRNA detection.
ABSTRACT: Background:The efficacy of cervical cancer screening programs is dependent on the participation rate. To increase participation among women not attending cervical cancer screening, self-collected samples for detection of high-risk human papillomavirus (hr-HPV) may be an option.The aims of this study were: to investigate the response rate to sending a self-collected vaginal sample for hr-HPV mRNA detection to long-term non-attendees; the compliance with follow-up among women positive for HPV in the self-sample; the prevalence of cervical dysplasia (high grade squamous intraepithelial lesion (HSIL), atypical squamous cells that cannot exclude HSIL (ASC-H) or adenocarcinoma in situ (AIS)) or cancer among the responders; as well as to explore reasons for not returning a self-sample. Methods:A vaginal self-sampling kit was sent to 6023 women aged 30-70?years who had not provided a cervical screening sample for ?7?years in the Region of Skåne, Sweden in November and December 2017. The self-sample was analyzed by Aptima HPV mRNA assay (Hologic). All vaginal self-samples returned no later than May 31, 2018 were included in the study. Follow-up of the results was registered until January 31, 2019 with a follow-up time varying between eight to 14?months. Women positive for hr-HPV mRNA were invited for a follow-up examination. This examination consisted of a cervical sample for cytological analysis and renewed Aptima HPV mRNA testing. Two hundred thirty-five women who had not returned the self-sample were randomly selected for telephone interviews, in order to explore their reasons. Results:The response rate for the self-collected vaginal hr-HPV sample was 13.2% [(797/6023), 95% CI 12.4-14.1%] and 9.9% [(79/796), 95% CI 7.9-12.2%] were positive for hr-HPV mRNA. The prevalence of severe dysplasia or cancer in the whole group of responders was 1.3% [(10/796), 95% CI 0.6-2.3%], with a cervical cancer prevalence of 0.4% [(3/796), 95% CI 0.1-1.1%]. Only 27 women participated in the telephone interviews, no particular reason for not returning self-samples was observed. Conclusions:Self-collected vaginal hr-HPV samples increased participation in the cervical cancer screening among long-term non-attendees. The prevalence of cervical cancer was almost seven times higher for long-term non-attendees than in the organized screening population.
Project description:OBJECTIVES:Human papillomavirus (HPV) testing in cervical screening offers the potential for self-sampling to improve uptake among non-attenders. High-risk (HR) HPV detection in urine shows promise, but few studies have examined its sensitivity for cervical intraepithelial neoplasia (CIN2+) detection compared with standard cervical samples. The aims of this cross-sectional study were to optimise conditions for urine testing for HPV detection; to determine concordance for HR-HPV detection in matched urine, vaginal and cervical samples; to compare the sensitivity of HR-HPV testing for the detection of CIN2+ in matched samples; and to determine the acceptability of urine testing for cervical screening. DESIGN:Cross-sectional study. SETTING:Secondary care colposcopy clinic in North West England. PARTICIPANTS:Women aged 25 years of age or older, attending colposcopy clinic for management of abnormal cervical screening results or a suspicious-looking cervix. In total, 104 women took part in the study. Triple matched samples were available for 79 and 66 women using Abbott RealTime (ART) and Roche Cobas 4800 (RC), respectively. INTERVENTION:Self-collected urine and vaginal samples and practitioner-obtained cervical samples were tested for HR-HPV by ART and RC assays, including comparison of neat and preservative-fixed urine. Colposcopic opinion was recorded and directed cervical biopsies taken if clinically indicated. The acceptability of self-testing was evaluated by questionnaire. PRIMARY OUTCOME MEASURE:The sensitivity of urine to detect underlying CIN2+. SECONDARY OUTCOME MEASURES:The comparative sensitivity of vaginal and cervical samples to detect CIN2+; the acceptability of urine sampling. RESULTS:Preservative-fixed, but not neat urine, showed good concordance with vaginal samples for the detection of HR-HPV. The sensitivity for detecting CIN2+ was 15/18 (83%) for urine and 16/18 (89%) for cervical and vaginal samples by ART, and 15/17 (88%) for all samples by RC. Urine-based testing was broadly acceptable to women. CONCLUSIONS:Urinary HR-HPV detection offers an alternative strategy of cervical screening. Larger studies to determine its clinical utility are warranted.
Project description:Human papillomavirus (HPV) testing on vaginal self-collected and cervical clinician-collected specimens shows comparable performance. Self-sampling on FTA cards is suitable for women residing in rural settings or not attending regular screening and increases participation rate in the cervical cancer screening programme. We aimed to investigate and compare high-risk (HR)-HPV prevalence in clinician-collected and self-collected genital specimens as well as two different HPV tests on the clinician collected samples. A total of 737 women were recruited from two sites, a community health clinic (n = 413) and a referral clinic (n = 324) in the Eastern Cape Province. Cervical clinician-collected (FTA cards and Digene transport medium) and vaginal self-collected specimens were tested for HR-HPV using the hpVIR assay (FTA cards) and Hybrid Capture-2 (Digene transport medium). There was no significant difference in HR-HPV positivity between clinician-collected and self-collected specimens among women from the community-based clinic (26.4% vs 27.9%, p = 0.601) or the referral clinic (83.6% vs 79.9%, p = 0.222). HPV16, HPV35, and HPV33/52/58 group were the most frequently detected genotypes at both study sites. Self-sampling for HPV testing received a high positive response of acceptance (77.2% in the community-based clinic and 83.0% in referral clinic). The overall agreement between hpVIR assay and HC-2 was 87.7% (k = 0.754). The study found good agreement between clinician-collected and self-collected genital specimens. Self-collection can have a positive impact on a cervical screening program in South Africa by increasing coverage of women in rural areas, in particular those unable to visit the clinics and women attending clinics where cytology-based programs are not functioning effectively.
Project description:Background: Offering self-sampling of cervico-vaginal material for human papillomavirus (HPV) testing is an effective method to increase the coverage in cervical screening programmes. Molecular triage directly on HPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a methylation classifier for detection of precancer (CIN3) or cancer, applicable to self-samples obtained by different devices. Findings: Genome-wide DNA methylation profiling of HPV-positive self-samples revealed 12 methylation targets for CIN3 detection. Multiplex quantitative methylation-specific PCR of these targets yielded a 3-gene methylation classifier (ASCL1, LHX8 and ST6GALNAC5), showing a very good clinical performance for CIN3 detection in both lavage (AUC=0.88; sensitivity=74%; specificity=79%) and brush (AUC=0.90; sensitivity=88%; specificity=81%) self-samples in the validation set. All self-samples from women with cervical cancer scored methylation-positive. Conclusion: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on self-samples from HPV-positive women. Overall design: 68 self-sampled cervico-vaginal specimens were analysed by Illumina Infinium HumanMethylation450 BeadChip. This series comprised 28 HPV-positive controls, 36 from women with a CIN3 (precancer) and 4 from women with cervical squamous cell carcinoma.
Project description:Cervical cancer is the fourth most common cancer among women worldwide and screening pro-grams increase detection rate and survivability. Molecular screening of presence of human papil-loma viruses (HPV) as alternatives to physical examinations offers cost-efficient solutions and can be performed on self-collected samples. A persistent infection with HPV is necessary but not sufficient to develop cancer and additional biomarkers are needed to increase the precision. We have analyzed protein biomarkers found in self-collected dried cervico-vaginal fluid (CVF) from both controls and women with cervical cancer pre-stages.
Project description:<h4>Background</h4>Cervical cancer screening coverage remains insufficient in most countries. Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus (HR-HPV) testing is effective and cost-effective in increasing participation in cervical cancer screening.<h4>Methods</h4>In March 2012, 6000 unscreened women aged 30-65 years, living in a French region covered by a screening programme, who had not responded to an initial invitation to have a Pap smear were equally randomised to three groups: 'no intervention'; 'recall', women received a letter to have a Pap smear; and 'self-sampling', women received a self-sampling kit to return to a centralised virology laboratory for PCR-based HPV testing.<h4>Results</h4>Participation was higher in the 'self-sampling' than in the 'no intervention' group (22.5% vs 9.9%, P<0.0001; OR 2.64) and 'recall' group (11.7%, P<0.0001; OR 2.20). In the 'self-sampling' group, 320 used the self-sampling kit; for 44 of these women with positive HR-HPV test results, 40 had the recommended triage Pap smear. The ICER per extra screened woman was 77.8[euro ] and 63.2[euro ] for the 'recall' and 'self-sampling' groups, respectively, relative to the 'no intervention' group.<h4>Conclusions</h4>Offering an in-home, return-mail kit for vaginal self-sampling with a dry swab is more effective and cost-effective than a recall letter in increasing participation in cervical cancer screening.
Project description:<h4>Background</h4>Incidence and mortality rates of cervical cancer in Bolivia are the highest in Latin America. Vaginal cell self-sampling can improve screening coverage. Information on common reasons for low screening coverage and preferences for future screening are essential to reduce cervical cancer incidence. We aimed to evaluate the knowledge about human papillomavirus (HPV) and cervical cancer of Bolivian women from urban, peri-urban and rural areas of Cochabamba and to determine their degree of acceptability and confidence towards vaginal HPV self-sampling. In addition, we assessed the impact of self-sampling on cervical cancer screening coverage in a selected peri-urban area.<h4>Methods</h4>We gathered information from women living in urban, peri-urban and rural areas of Cochabamba province in Bolivia using two different structured questionnaires. In Survey1, we collected information from 222 women about their knowledge on HPV and cervical cancer. In Survey 2, the acceptance and confidence towards vaginal HPV self-sampling compared to the physician-sampling was assessed in 221 women. A non-probabilistic stratified sampling by areas was carried out for the two questionnaires. In the third phase of the study, we determined the impact of HPV self-sampling collection on screening coverage in a peri-urban area of Cochabamba.<h4>Results</h4>Bolivian women knew little or nothing about cervical cancer and HPV infection in all areas. They all found self-sampling collection easier to perform (86.9 to 93.2%) and more comfortable (79.4 to 83.3%) compared to physician sampling. Sampling accuracy to detect cervical cancer was probably higher in their point of view when it was taken by physician (35.1 to 63.5%). However in rural areas women preferred self-sampling. Accordingly, the campaign of vaginal HPV self-sampling in this peri-urban area increased screening coverage, reaching in three months the annual rate average.<h4>Conclusions</h4>The knowledge about cervical cancer and HPV infection is poor in Bolivia. Despite greater acceptance of the vaginal HPV self-sampling in all areas, women kept greater confidence in the screening performed by the gynecologist although HPV self-sampling improved coverage rate.
Project description:Cervical cancer, nearly all cases of which are caused by one of several high-risk strains of the human papillomavirus (hr-HPV), leads to significant morbidity and mortality in individuals with a cervix. Trans masculine (TM) individuals were born with female reproductive organs and identify as male, man, transgender man, or another diverse gender identity different from their female assigned sex at birth. Routine preventive sexual health screening of TM patients is recommended, including screening for cervical cancer and other sexually transmitted infections (STIs); however, as many as one in three TM patients are not up-to-date per recommended U.S.Among cisgender (non-transgender) women, self-swab hr.-HPV DNA testing as a primary cervical cancer screening method and self-swab specimen collection for other STIs have high levels of acceptability. No study has yet been conducted to compare the performance and acceptability of self- and provider-collected swabs for hr.-HPV DNA testing and other STIs in TM patients.This article describes the study protocol for a mixed-methods biobehavioral investigation enrolling 150 sexually active TM to (1) assess the clinical performance and acceptability of a vaginal self-swab for hr.-HPV DNA testing compared to provider cervical swab and cervical cytology, and (2) gather acceptability data on self-collected specimens for other STIs. Study participation entails a one-time clinical visit at Fenway Health in Boston, MA comprised of informed consent, quantitative assessment, venipuncture for syphilis testing and HIV (Rapid OraQuick) testing, randomization, collection of biological specimens/biomarkers, participant and provider satisfaction survey, and qualitative exit interview. Participants are compensated $100. The primary study outcomes are concordance (kappa statistic) and performance (sensitivity and specificity) of self-collected vaginal HPV DNA specimens vs provider-collected cervical HPV swabs as a gold standard.This study addresses critical gaps in current clinical knowledge of sexual health in TM patients, including comparing alternative strategies for screening and diagnosis of cervical cancer, hr.-HPV, and other STIs. Findings have implications for improving the delivery of sexual health screening to this often overlooked and underserved patient population. Less-invasive patient-centered strategies may also generalize to other at-risk cisgender female populations that face barriers to timely and needed STI and cervical cancer screening.ClinicalTrials.gov ID: NCT02401867.
Project description:High-Risk Human papillomavirus (HR-HPV) full genotyping methods have been described as of great potential use in epidemiology and preventive strategies, including cervical cancer screening and HPV vaccination. We characterized the prevalence and distribution of HR-HPV genotypes in cervico-vaginal samples obtained from the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. HR-HPV genotyping was performed using Anyplex™ II HPV-HR Detection kit in 105,458 women enrolled between August 2016 and December 2017. HR-HPVs were detected in 10,665 women (10.2%) with a prevalence ranging from 6.2 to 17.1% depending on age, and from 8.7 to 10.7% depending on geographical location. Multiple infections with two or more HR-HPVs were detected in 2736 (25.7%) of HR-HPV women ranging from 16.5 to 31.0% depending on age. Amongst HR-HPV positive women, HPV-16 (17.5%), HPV-39 (16.7%), HPV-31 (15.0%), HPV-68 (13.2%), HPV-52 (10.7%) and HPV-51 (10.6%) were the most common genotypes in our population, being HPV-16 more frequent in women aged from 30 to 45 years and HPV-39 in 50-65 years. Results also show that HPV16/18 are present in 22.1% and HPV16/18/31/33/45/52/58 in 47.6% of HR-HPV positive women. This is the largest study on HR-HPV genotyping for Cervical Cancer Screening in European populations and provides critical data for program management and vaccine policy.
Project description:Background The incidence of cervical cancer is up to sixfold higher among First Nation women in Canada than in the general population. This is probably due to lower participation rates in cervical cancer prevention programmes. Objective To raise screening participation in this underserved population by launching an alternative approach to (Pap)anicolaou testing in a clinic-namely, vaginal self-sampling followed by human papillomavirus (HPV) diagnostics. Methods Good relationships were established with a First Nation community of the Northern Superior region in Northwest Ontario, and then 49 community women, aged 25-59, were recruited, who provided a vaginal self-sample and answered a questionnaire. Frequency distributions and cross-tabulations were used to summarise the data. Associations between categorical variables were assessed using the ?(2) test of association, or the Goodman-Kruskal ? if both variables had ordered categories. Self-collected samples were tested for integrity and HPV using optimised molecular biological methods. Results The majority of participants (87.2%) were amenable to future HPV screening by self-sampling. This finding was independent of age, educational level and a previous history of abnormal Pap tests. Interestingly, the preferred way to learn about sexual health remained through interaction with healthcare professionals. As defined by the presence of a housekeeping gene, self-sample integrity was high (96%). Using polymerase chain reaction-based Luminex typing, the overall HPV positivity was 28.6% (ie, with either a low- or high-risk type) and 16.3% were infected with a high-risk type such as HPV16. Conclusion In this pilot study of First Nation women, self-sampling and HPV testing was well received and self-sample quality was excellent. A larger survey to be conducted in other Northern Superior communities in Northwest Ontario will determine whether this approach could become a viable screening strategy for First Nation women.
Project description:Background:Vaginal dysbiosis may paly role in increased risk of human papillomavirus (HPV) infection. This study aims to explore potential vaginal microbiome biomarkers, to predict persistent high-risk HPV (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) 2+, and to find novel treatment targets for HPV infection. Methods:A total of 329 women aged 20-69 were enrolled in this study, including 59 with cervical persistent HPV infection irrespective of cytology status (group A), 139 with incident HPV infection (group B), and 131 without HPV infection (group C). Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. Results:In genus level, the relative abundance of Prevotella, Porphyromonas and Enterococcus were significantly the highest in group A, while Bacteroides was the lowest in group A. In species level, we found the relative abundance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis were the highest in group A while Lactobacillus iners was significantly under-represented in group A than the other two, and Prevotella disiens was over-represented in group C than the other two groups. Conclusions:A predominance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis with a concomitant paucity of Lactobacillus iners and Prevotella disiens may relate to HPV persistent infection. Furthermore, the relative abundance of Prevotella bivia being over 0.05554% with Prevotella disiens being under 0.02196% may be a good predictor for appearance CIN2+ for those diagnosed with the other 12 types of HR-HPV persistent infection but normal ThinPrep cytology test (TCT) testing. The exact molecular mechanism of the vaginal microbiome in the course of persistent HR-HPV infection and cervical neoplasia should be further explored. Future research should include intervention of vaginal microbiome composition to reverse the course of HR-HPV infection and the natural history of cervical neoplasia.