A Randomized Comparison of Different Vaginal Self-sampling Devices and Urine for Human Papillomavirus Testing-Predictors 5.1.

BACKGROUND: Human papillomavirus (HPV)-based screening is rapidly replacing cytology as the cervical screening modality of choice. In addition to being more sensitive than cytology, it can be done on self-collected vaginal or urine samples. This study will compare the high-risk HPV positivity rates and sensitivity of self-collected vaginal samples using four different collection devices and a urine sample. METHODS: A total of 620 women referred for colposcopy were invited to provide an initial stream urine sample collected with the Colli-Pee device and take two vaginal self-samples, using either a dry flocked swab (DF) and a wet dacron swab (WD), or a HerSwab (HS) and Qvintip (QT) device. HPV testing was performed by the BD Onclarity HPV Assay. RESULTS: A total of 600 vaginal sample pairs were suitable for analysis, and 505 were accompanied by a urine sample. Similar positivity rates and sensitivities for CIN2+ and CIN3+ were seen for DF, WD, and urine, but lower values were seen for QT and HS. No clear user preferences were seen between devices, but women found urine easiest to collect, and were more confident they had taken the sample correctly. The lowest confidence in collection was reported for HS. CONCLUSIONS: Urine, a DF swab, and WD swab all performed well and were well received by the women, whereas the Qvintip and HerSwab devices were less satisfactory. IMPACT: This is the first study to compare five self-sampling methods in the same women taken at the same time. It supports wider use of urine or vaginal self-sampling for cervical screening.

Evaluation of Dried Blood Spots and Oral Fluids as Alternatives to Serum for Human Papillomavirus Antibody Surveillance.

Human papillomavirus (HPV) vaccination elicits high-titer genotype-specific antibody responses that are associated with a reduced risk of cervical disease caused by vaccine-incorporated genotypes. Our objective was to evaluate dried blood spots (DBSs) and oral mucosal transudate (OMT) as alternative samples to serum to confirm HPV vaccine antibody status. A study was carried out to evaluate the feasibility of detecting HPV16 and HPV18 antibodies in OMT, DBSs, and sera among women who self-reported being unvaccinated or fully vaccinated with the HPV vaccine. Serum had the highest sensitivity (100%) for detection of antibodies against both HPV16 and HPV18 but the lowest specificity, due to the detection of natural infection antibodies in 16% of unvaccinated women. Conversely, DBSs and OMT had lower sensitivity (96% and 82%, respectively) but high specificity (98%). We confirmed that these antibodies were functional (i.e., neutralizing) and that their detection was quantitatively reproducible and well correlated between sample types when normalized to IgG content. DBSs and OMT are appropriate alternative sample types for HPV vaccine surveillance. These alternative sample types warrant consideration for the purposes of cervical screening, diagnosis, and management, but more work will be needed to establish the stringent parameters required for such application.IMPORTANCE Human papillomavirus (HPV) is the causative agent of cervical and other anogenital cancers. HPV vaccination, primarily targeted at young girls before the age of sexual debut, is starting to demonstrate population-level declines in HPV infection and early disease associated with vaccine-incorporated genotypes. Monitoring young women for vaccine-specific antibody is important for vaccine surveillance and may be useful as an adjunct test within a cervical screening context. We evaluated serum, dried blood spots, and oral fluid as potential samples for such applications and report robust measures of diagnostic accuracy. This is the first time a direct comparison of alternative sample types has been made between vaccinated and unvaccinated women for the detection and quantitation of HPV antibodies.

A comparison of different human papillomavirus tests in PreservCyt versus SurePath in a referral population-PREDICTORS 4.

BACKGROUND: Two transport media, PreservCyt and SurePath, are widely used for cervical cytology screening. There are concerns that they may perform differently for HPV testing. OBJECTIVES: A comparison of the performance of six different HPV tests in SurePath and PreservCyt in a referral population using two samples from each woman. The primary goal was to compare the performance of each test in the two media. Comparisons between assays and viral load comparisons between media were secondary aims. STUDY DESIGN: Two cervical samples were collected in random order at the same visit in women with abnormal cytology. One sample was placed in 20ml of PreservCyt and the other in 10ml of SurePath. Aliquots were taken for 4 DNA based tests: digene HC2 High-Risk HPV DNA Test, Abbott Realtime, BD Onclarity and Genera PapType, an RNA based test-: Hologic Aptima and a protein test: OncoHealth. RESULTS: 630 sample pairs were included in the analyses. For all tests except the protein test sensitivities were in excess of 90% for CIN2+ and 95% for CIN3+ for both media and with no significant differences except for a lower sensitivity for CIN2+ of Aptima in SurePath (93% vs 98%, P=0.005). Specificity for

A randomized controlled trial in non-responders from Newcastle upon Tyne invited to return a self-sample for Human Papillomavirus testing versus repeat invitation for cervical screening.

BACKGROUND: Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. OBJECTIVES: To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. METHODS: 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). RESULTS: 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90-2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. CONCLUSION: Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result.

Attitudes towards cytology and human papillomavirus self-sample collection for cervical screening among Hindu women in London, UK: a mixed methods study.

OBJECTIVES: To explore the attitudes, views and understanding of women attending a Hindu temple in London, UK towards cervical screening, human papillomavirus (HPV) testing and two HPV self-sample collection devices: the Dacron swab and Evalyn(®) brush. METHODS: A mixed methods design comprising a survey and four focus groups was adopted. Focus group discussions were recorded and transcribed verbatim and explored using thematic framework analysis. RESULTS: A total of 185 Hindu women completed surveys and 23 attended focus groups. Of the respondents 75% aged 25-64 years reported having cervical screening within the last 5 years; 85% had attended college or university. Familiar barriers to attendance for screening were identified: fear of pain and the test result, embarrassment, screener's attitude, inconvenient appointment times and difficulty with child care. Additional barriers cited included age and country of birth, with older and Indian-born women thought to be less likely to attend for screening. Self-collected sampling had a mixed reception. Women were not confident that their sample would be as good as a clinician sample and expressed concern about the impact that a positive HPV result might have on their relationships. CONCLUSIONS: Screening attendance in this highly educated group of Hindu women was slightly lower than in the general population (75% of women aged 25-64 years had been screened in the last 5 years compared with 79% in England as a whole). Familiar barriers to screening were identified. Women felt able to collect their own sample for HPV testing with a Dacron swab but lacked confidence that it would be as good as that obtained by a clinician.

Individual detection of 14 high risk human papilloma virus genotypes by the PapType test for the prediction of high grade cervical lesions.

BACKGROUND: HR HPV genotypes when assayed collectively, achieve high sensitivity but low specificity for the prediction of CIN2+. Knowledge of the specific genotypes in an infection may facilitate the use of HR HPV detection in routine clinical practice. OBJECTIVES: To compare the rate of HR HPV detection and the accuracy of CIN2+ prediction between PapType test (Genera Biosystems) and other commercially available HR HPV assays, and to examine the value of full HPV genotyping. STUDY DESIGN: PreservCyt samples from 1099 women referred for abnormal cervical cytology were used. CIN2+ was chosen as the primary end-point but CIN3+ was also evaluated. A hierarchy of HR HPV genotypes was created using PPV and this was used to create 3 groups of genotypes with potentially different management. RESULTS: The PapType assay has a specificity of 22.4% and a sensitivity of 94.6% for CIN2+ prediction. Classification into Groups A (HPV33 and HPV16, very highly predictive), B (HPV31, 18, 52, 35, 58, 51 highly predictive) and C (HPV68, 45, 39, 66, 56, 59, intermediate predictive) could double the specificity (44.5%) but only slightly reduce the sensitivity for CIN2+ (91.5%) and CIN3+ (94.0%). CONCLUSIONS: The PapType assay is a simple, reproducible and effective test for HR HPV detection and genotyping. HPV 33 was found to have a very high PPV and should therefore be managed as for HPV16.

Comparison of human papillomavirus testing strategies for triage of women referred with low-grade cytological abnormalities.

AIM: To compare triage strategies using different human papillomavirus (HPV) consensus and genotyping tests and a p16(INK4a) test. METHODS: 1228 women referred with a borderline or single mildly dyskaryotic smear. Samples were taken at colposcopy using PreservCyt. Tests included Hybrid Capture 2, Abbott RealTime PCR, BD HPV, Cobas 4800, PreTect HPV-Proofer, APTIMA and p16(INK4a). Results were based on the worst histology within 9 months. RESULTS: 97/1228 (7.9%) women had CIN3+ (203/1228 (17%) CIN2+). HPV testing alone using Hybrid Capture 2, Abbott RealTime PCR, BD HPV, Cobas 4800 or APTIMA had a sensitivity for CIN3+ ranging from 99.0% to 100.0% and specificity for

Barriers to cervical screening in women who have experienced sexual abuse: an exploratory study.

OBJECTIVES: To explore self-reported cervical screening history and barriers to attendance among women who have been sexually abused and to identify measures to improve the experience of cervical screening for these women. METHODS: Women visiting the website of the National Association for People Abused in Childhood (NAPAC), who had been sexually abused, were invited to complete a survey of their views and experiences of cervical screening. This included closed questions on demographic characteristics and cervical screening attendance, open questions on barriers to screening, and the opportunity to submit suggestions to improve this experience for women who have been sexually abused. Content analysis was used to code responses to the open questions. Four women also participated in a discussion group. RESULTS: Overall, 135 women completed the closed questions and 124 provided open-ended responses. 77.5% of responding women who were eligible for cervical screening in England had ever attended, 48.5% at least once in the previous 5 years, but 42.1% of women aged 25-49 within 3 years. A total of nine higher order themes were identified related to barriers to screening, one related to intention to attend screening and five related to suggestions to improve screening. CONCLUSIONS: This study supports the idea that women who have experienced sexual abuse are less likely to attend for regular cervical screening, with under half screened in the last 5 years compared to the National Health Service Cervical Screening Programme figure of 78.6%. Suggestions to improve the experience for abused women focused on communication, safety, trust and sharing control. Further research in this area is warranted to ensure that this at-risk population is appropriately served by cervical screening.

Comparison of seven tests for high-grade cervical intraepithelial neoplasia in women with abnormal smears: the Predictors 2 study.

High-risk human papillomavirus (HPV) DNA/RNA testing provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Several new HPV tests are now available for this purpose, and a direct comparison of their properties is needed. Seven tests were evaluated with samples in liquid PreservCyt transport medium from 1,099 women referred for colposcopy: the Hybrid Capture 2 (Qiagen), Cobas (Roche), PreTect HPV-Proofer (NorChip), Aptima HPV (Gen-Probe), and Abbott RealTime assays, the BD HPV test, and CINtec p16(INK4a) cytology (mtm laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology found on either the biopsy or the treatment specimen after central review. Three hundred fifty-nine women (32.7%) had CIN grade 2+ (CIN2+), with 224 (20.4%) having CIN3+. For detection of CIN2+, Hybrid Capture 2 had 96.3% sensitivity, 19.5% specificity, and 37.4% PPV. Cobas had 95.2% sensitivity, 24.0% specificity, and 37.6% PPV. The BD HPV test had 95.0% sensitivity, 24.2% specificity, and 37.8% PPV. Abbott RealTime had 93.3% sensitivity, 27.3% specificity, and 38.2% PPV. Aptima had 95.3% sensitivity, 28.8% specificity, and 39.3% PPV. PreTect HPV-Proofer had 74.1% sensitivity, 70.8% specificity, and 55.4% PPV. CINtec p16(INK4a) cytology had 85.7% sensitivity, 54.7% specificity, and 49.1% PPV. Cytology of a specimen taken at colposcopy (mild dyskaryosis or worse) had 88.9% sensitivity, 58.1% specificity, and 50.7% PPV. Our study confirms that, in a referral setting, HPV testing by a number of different tests provides high sensitivity for high-grade disease. Further work is needed to confirm these findings in a routine screening setting.

Exploring the acceptability of two self-sampling devices for human papillomavirus testing in the cervical screening context: a qualitative study of Muslim women in London.

OBJECTIVES: We explored Muslim women's attitudes to self-sampling for human papillomavirus (HPV) in the context of cervical cancer screening and their responses to two self-sampling devices. SETTING: A Muslim community centre in north-east London. METHODS: Following a talk given on the subject of cervical cancer and HPV at the community centre, 28 women were recruited to take part in three focus group discussions. The discussion covered cervical screening, self-sampling and HPV testing. Women were also asked for their responses to a swab self-sampling kit and a cervico-vaginal lavage device. Discussions were recorded and transcribed verbatim and the qualitative data were analysed using Framework Analysis. RESULTS: Participants were generally positive about cervical screening but acknowledged that some women in their community were reluctant to attend because of embarrassment, language difficulties, fear or because they were unmarried and did not want to communicate implicit messages about being sexually active. Self-sampling met a mixed response - women were concerned about not doing the test correctly, but thought that it might overcome barriers to screening for some women. HPV testing itself was thought to raise potentially difficult issues relating to trust and fidelity within marriages. Although most women said they would prefer to continue to have screening by a health professional, if they were to perform self-sampling, there was overwhelming preference for the swab over the lavage kit. CONCLUSIONS: There was limited enthusiasm for self-sampling in this group of Muslim women who had mostly attended for cervical screening, but a clear preference for a swab rather than a cervico-vaginal lavage.