Louise Cadman

Comparison of Predictors for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears

Background: The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). This study compared the sensitivity and specificity of several adjunctive tests for the detection of high-grade CIN in a population referred to colposcopy because of abnormal cytology. Methods: 953 women participated in the study. Up to seven tests were carried out on a liquid PreservCyt sample: Hybrid Capture II (Digene), Amplicor (Roche), PreTect HPV-Proofer (NorChip), APTIMA HPV assay (Gen-Probe), Linear Array (Roche), Clinical-Arrays (Genomica), and CINtec p16INK4a Cytology (mtm Laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology seen on either the biopsy or the treatment specimen after central review. Results: 273 (28.6%) women had high-grade disease (CIN2+) on worst histology, with 193 (20.2%) having CIN3+. For the detection of CIN2+, Hybrid Capture II had a sensitivity of 99.6%, specificity of 28.4%, and PPV of 36.1%. Amplicor had a sensitivity of 98.9%, specificity of 21.7%, and PPV of 33.5%. PreTect HPV-Proofer had a sensitivity of 73.6%, specificity of 73.1%, and PPV of 52.0%. APTIMA had a sensitivity of 95.2%, specificity of 42.2%, and PPV of 39.9%. CINtec p16INK4a Cytology had a sensitivity of 83.0%, specificity of 68.7%, and PPV of 52.3%. Linear Array had a sensitivity of 98.2%, specificity of 32.8%, and PPV of 37.7%. Clinical-Arrays had a sensitivity of 80.9%, specificity of 37.1%, and PPV of 33.0%. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3033–42)

Testing positive for Human Papillomavirus in routine cervical screening: examination of psychosocial impact

Objective  To examine the psychosocial impact of testing positive for high risk human papillomavirus (HPV) among women attending primary cervical screening.

Comparison of Seven Tests for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears: the Predictors 2 Study

ABSTRACT 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 p16INK4a 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 p16INK4a 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.

Comparing the performance of six human papillomavirus tests in a screening population

Background:Several new assays have been developed for high-risk HPV testing of cervical samples; we compare six HPV tests in a screening population.Methods:Residual material from liquid-based PreservCyt samples was assayed. Four tests (Hybrid Capture 2, Cobas, Abbott and Becton-Dickinson (BD)) measured HPV DNA while two used RNA (APTIMA and NorChip).Results:Positivity rates ranged from 13.4 to 16.3% for the DNA-based tests with a significantly lower positivity rate for the Abbott assay. The Gen-Probe APTIMA assay was positive in 10.3% of women, which was significantly lower than all the DNA tests; the NorChip PreTect HPV-Proofer test was much lower at 5.2%. 40 CIN2+ cases were identified, of which 19 were CIN3+. All CIN3+ cases were HPV positive by all tests except for one, which was negative by the Abbott assay and five which were negative by the NorChip test.Conclusion:All HPV tests except NorChip showed high sensitivity for high-grade lesions positive by cytology, suggesting co-testing is unnecessary when using HPV tests. Positivity rates in cytology-negative specimens were similar for the DNA-based tests, but lower for the APTIMA test suggesting this maintains the high sensitivity of DNA tests, but with better specificity.

HPV self-sampling as an alternative strategy in non-attenders for cervical screening – a randomised controlled trial

Background:A randomised trial to ascertain whether women who do not attend for cervical screening are more likely to respond to the opportunity to collect a self-sample for human papillomavirus (HPV) testing, or to a further invitation to attend for cervical screening.Methods:The study was carried out in a Primary Care Trust (PCT) in London between June 2009 and December 2009. In total, 3000 women were randomly selected from persistent non-responders (i.e., who had not responded to at least two invitations to attend for screening). The women were randomised on a 1 : 1 basis to either receive an HPV self-sampling kit or a further invitation to attend for cervical cytology. The main outcome measures were (1) percentage of women attending for cervical cytology compared with those returning a self-sample HPV test or attending for cytology subsequent to receiving the kit and (2) percentage of those testing positive for HPV who attended further investigation.Results:The total response in the self-sampling group for screening was 10.2%. Of the 1500 women in the control group sent a further invitation for cervical screening, 4.5% attended for cytology screening. This difference is highly statistically significant (P<0.0001). Of the 8 women who tested positive for HPV, 7 attended for a cervical smear and had a concurrent colposcopy. Three of these (43%) had high-grade disease (defined as CIN 2+), with one found to have an invasive cancer (stage 1b) and one CIN 3.Conclusions:The value of this intervention relies on the detection of high-grade CIN and early stage cancer with a good prognosis. The relatively high yield of abnormalities found is consistent with that expected among a hard to reach and relatively high-risk group of women. Our study suggests that self-sampling could increase participation among non-responders in England, but further work is needed to ascertain whether the low response rate seen here is likely to be representative of the rest of the country. Other studies are needed to investigate the response to self-sampling in different demographic and geographic settings.

Acceptability of unsupervised HPV self-sampling using written instructions.

Objectives The study measured the acceptability of self-sampling for human papillomavirus (HPV) testing in the context of cervical cancer screening. Women carried out self-sampling unsupervised, using a written instruction sheet. Setting Participants were women attending either a family planning clinic or a primary care trust for routine cervical screening. Methods Women (n = 902) carried out self-sampling for HPV testing and then a clinician did a routine cervical smear and HPV test. Immediately after having the two tests, participants completed a measure of acceptability for both tests, and answered questions about ease of using the instruction sheet and willingness to use self-sampling in the future. Results The majority of women found self-sampling more acceptable than the clinician-administered test, but there was a lack of confidence that the test had been done correctly. Significant demographic differences in attitudes were found, with married women having more favourable attitudes towards self-sampling than single women, and Asian women having more negative attitudes than women in other ethnic groups. Intention to use self-sampling in the future was very high across all demographic groups. Conclusion Self-sampling for HPV testing was highly acceptable in this large and demographically diverse sample, and women were able to carry out the test alone, using simple written instructions. Consistent with previous studies, women were concerned about doing the test properly and this issue will need to be addressed if self-sampling is introduced. More work is needed to see whether the demographic differences we found are robust and to identify reasons for lower acceptability among single women and those from Asian background.

Long-term follow-up of cervical abnormalities among women screened by HPV testing and cytology—results from the Hammersmith study

Several studies have shown that HPV testing is substantially more sensitive than cytology for primary cervical screening. However, less data exist concerning the duration of protection afforded by a negative HPV test compared to a normal cytological outcome. Here we report the long‐term findings from the Hammersmith study in women aged 35 or more. HPV testing by Hybrid Capture II was performed on all available samples from the baseline screening visit. Passive surveillance of subsequent cytology screening results for the 2,982 women in the study was undertaken using a national registry. Histological outcomes were sought for all women with abnormal smears. The primary outcome was duration of protection against histologically confirmed CIN2+ afforded by a negative HPV test compared to normal cytology. 2,516 women had at least one further smear at least 1 year after entry and 20 new cases of CIN2+ were identified during a median follow‐up of 6.4 years. Including disease identified at baseline, the risk of developing CIN2+ at 1, 5 and 9 years after a normal cytology was 0.33%, 0.83% and 2.20% respectively whereas it was 0.19%, 0.42% and 1.88% after a negative HPV test. HPV testing offered excellent protection from CIN2+ for at least 6 years after a negative test, whereas the protection from cytology began to wane after about 3 years. Substantially more CIN2+ lesions were found in the follow‐up period in those initially HPV positive compared to those HPV negative (HR = 6.52, p = 0.001), whereas there was little difference according to initial cytology (HR = 1.64, p = 0.51).

Attitudes to self-sampling for HPV among Indian, Pakistani, African-Caribbean and white British women in Manchester, UK

Objective: To examine attitudes to self-sampling for human papillomavirus (HPV) testing among women from contrasting ethnic groups. Setting: Manchester, UK. Methods: Two hundred women of Indian, Pakistani, African-Caribbean and white British origin were recruited from social and community groups to participate in a questionnaire survey. The questionnaire included items on attitudes to self-sampling and intention to use the test. Results: Willingness to try to use the test was high, and women did not foresee religious or cultural barriers to self-sampling; however, a large proportion of women were concerned about doing the test properly. This concern was greatest in the Indian and African-Caribbean groups. Conclusions: Although womens willingness to try self-sampling for HPV is encouraging, worries about carrying out the procedure correctly must be addressed if women are to feel confident about the results of self-sampling methods and reassured by a negative result.

Human papillomavirus testing by self-sampling: assessment of accuracy in an unsupervised clinical setting.

Objectives: To compare the performance and acceptability of unsupervised self-sampling with clinician sampling for high-risk human papillomavirus (HPV) types for the first time in a UK screening setting. Setting: Nine hundred and twenty women, from two demographically different centres, attending for routine cervical smear testing Methods: Women performed an unsupervised HPV self-test. Immediately afterwards, a doctor or nurse took an HPV test and cervical smear. Women with an abnormality on any test were offered colposcopy. Results: Twenty-one high-grade and 39 low-grade cervical intraepithelial neoplasias (CINs) were detected. The sensitivity for high-grade disease (CIN2+) for the self HPV test was 81% (95% confidence interval [CI] 60–92), clinician HPV test 100% (95% CI 85–100), cytology 81% (95% CI 60–92). The sensitivity of both HPV tests to detect high- and low-grade cervical neoplasia was much higher than that of cytology (self-test 77% [95%CI 65–86], clinician test 80% [95% CI 68–88], cytology 48% [95% CI 36–61]). For both high-grade alone, and high and low grades together, the specificity was significantly higher for cytology (greater than 95%) than either HPV test (between 82% and 87%). The self-test proved highly acceptable to women and they reported that the instructions were easy to understand irrespective of educational level. Conclusions: Our results suggest that it would be reasonable to offer HPV self-testing to women who are reluctant to attend for cervical smears. This approach should now be directly evaluated among women who have been non-attenders in a cervical screening programme.

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 womens 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.