Validation of a DNA methylation HPV triage classifier in a screening sample.

High-risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV-positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV-positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV-positive women on original screening specimens might be a valid approach with better performance than genotyping.

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests).

The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (≤CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening.

A DNA methylation classifier of cervical precancer based on human papillomavirus and human genes.

Testing for high-risk (hr) types of human papillomavirus (HPV) is highly sensitive as a screening test of high-grade cervical intraepithelial neoplastic (CIN2/3) disease, the precursor of cervical cancer. However, it has a relatively low specificity. Our objective was to develop a prediction rule with a higher specificity, using combinations of human and HPV DNA methylation. Exfoliated cervical specimens from colposcopy-referral cohorts in London were analyzed for DNA methylation levels by pyrosequencing in the L1 and L2 regions of HPV16, HPV18, HPV31 and human genes EPB41L3, DPYS and MAL. Samples from 1,493 hrHPV-positive women were assessed and of these 556 were found to have CIN2/3 at biopsy; 556 tested positive for HPV16 (323 CIN2/3), 201 for HPV18 (73 CIN2/3) and 202 for HPV31 (98 CIN2/3). The prediction rule included EPB41L3 and HPV and had area under curve 0.80 (95% CI 0.78-0.82). For 90% sensitivity, specificity was 36% (33-40) and positive predictive value (PPV) was 46% (43-48). By HPV type, 90% sensitivity corresponded to the following specificities and PPV, respectively: HPV16, 38% (32-45) and 67% (63-71); HPV18, 53% (45-62) and 52% (45-59); HPV31, 39% (31-49) and 58% (51-65); HPV16, 18 or 31, 44% (40-49) and 62% (59-65) and other hrHPV 17% (14-21) and 21% (18-24). We conclude that a methylation assay in hrHPV-positive women might improve PPV with minimal sensitivity loss.

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.

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.

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.

Determinants of Human Papillomavirus Vaccine Uptake by Adult Women Attending Cervical Cancer Screening in 9 European Countries.

INTRODUCTION: Human papillomavirus-vaccinated cohorts, irrespective of age, will likely reduce their subsequent screening requirements, thus opening opportunities for global cost reduction and program sustainability. The determinants of uptake and completion of a 3-dose human papillomavirus vaccination program by adult women in a European context were estimated. STUDY DESIGN: This was an intervention study. SETTING/PARTICIPANTS: Study participants were women aged 25-45 years, attending opportunistic or population-based cervical cancer screening in Belgium, Denmark, Finland, France, Germany, Slovenia, Spain, Sweden, and the United Kingdom between April 2016 and May 2018. INTERVENTION: Study participants completed a questionnaire on awareness and attitudes on adult female human papillomavirus vaccination and were invited to receive free human papillomavirus vaccination. MAIN OUTCOME MEASURES: Main outcome measures were acceptance, uptake, and completion of vaccination schedule. Determinants of vaccine uptake were explored using multilevel logistic models in 2019. RESULTS: Among 3,646 participants, 2,748 (range by country=50%-96%) accepted vaccination, and 2,151 (range=30%-93%) received the full vaccination course. The factors associated with higher vaccine acceptance were previous awareness of adult female (OR=1.22, 95% CI=1.00, 1.48) and male (OR=1.59, 95% CI=1.28, 1.97) vaccination. Women in stable relationships (OR=0.56, 95% CI=0.45, 0.69) or with higher educational level (OR=0.76, 95% CI=0.63, 0.93) were more likely to refuse vaccination. Recruitment by postal invitation versus personal invitation from a healthcare professional resulted in lower vaccine acceptance (OR=0.13, 95% CI=0.02, 0.76). Vaccination coverage of >70% of adolescent girls in national public programs was of borderline significance in predicting human papillomavirus vaccine uptake (OR=3.23, 95% CI=0.95, 10.97). The main reasons for vaccine refusal were vaccine safety concerns (range=30%-59%) and the need for more information on human papillomavirus vaccines (range=1%-72%). No safety issues were experienced by vaccinated women. CONCLUSIONS: Acceptance and schedule completion were largely dependent on recruitment method, achieved coverage of national vaccination programs, and personal relationship status. Knowledge of benefits and safety reassurance may be critical to expanding vaccination target ages. Study results suggest that there are no major opinion barriers in adult women to human papillomavirus vaccination, especially when vaccination is offered face to face in healthcare settings. TRIAL REGISTRATION: EudraCT Number 2014-003177-42.

Performance of the Abbott RealTime high-risk HPV test in women with abnormal cervical cytology smears.

HPV DNA testing is known to be much more sensitive than cytology, but less specific. A range of HPV and related tests in 858 women referred for colposcopy because of an abnormal smear were evaluated to compare the performances of these tests. This article compared the Abbott test to other tests which had been previously evaluated. This test was a real true test for 14 high-risk HPV types. The Abbott test was found to be highly sensitive for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) (98.9%) with a specificity of 31.5%. These numbers were comparable with the Qiagen HC2 test, the Roche Linear Array and Amplicor tests, and the Gen-Probe APTIMA test. Differences between these tests appeared to be related mostly to the choice of cutoff level. An added feature of the Abbott test was the provision of type specific results for HPV 16 and 18.

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).

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%.

The future of cervical cancer prevention: human papillomavirus vaccines.

Human papillomavirus is recognised as the main cause of cervical cancer. Vaccines to protect against specific HPV types have been developed and a national HPV vaccination programme is due to begin in the UK in September 2008. Girls aged 12 to 13 years of age will be offered one of the vaccines, Cervarix, and it is hoped that it will offer them protection against over 70% of cervical cancer.

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.

Performance and Diagnostic Accuracy of a Urine-Based Human Papillomavirus Assay in a Referral Population.

Background: Human papillomavirus (HPV) testing from clinician-collected cervical and self-collected cervico-vaginal samples is more sensitive for detecting CIN2+/CIN3+ than cytology-based screening, stimulating interest in HPV testing from urine. The objective was to determine the performance of the Trovagene HPV test for the detection of CIN2+ from urine and PreservCyt cervical samples.Methods: Women referred for colposcopy at St Mary's Hospital (London, United Kingdom), following abnormal cytology, were recruited to this diagnostic accuracy study by convenience sampling (September 2011 to April 2013). A total of 501 paired urine and cervical samples were collected. Primary outcomes were sensitivity for CIN2+/CIN3+ and specificity for

Know the facts.

Vaccines to protect women against cervical cancer are already being licensed. An RCN leaflet gives nurses some of the facts about the links between HPV and cervical cancer.

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

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.

HPV33 DNA methylation measurement improves cervical pre-cancer risk estimation of an HPV16, HPV18, HPV31 and \textit{EPB41L3} methylation classifier.

BACKGROUND: Persistent infection %by with high risk human papillomavirus (hrHPV) types causes cervical cancer but most women who test positive are at very low risk of neoplasia. Strategies are needed which can retain high sensitivity of hrHPV testing but reduce the number of false-positives. We showed previously that a combination DNA methylation triage assay for HPV types 16, 18 and 31 and human gene EPB41L3 was useful to identify high grade cervical lesions. OBJECTIVE: Assess whether measurement of DNA methylation in HPV type 33 can improve the previous classifier. METHODS: A London colposcopy referral group of 1493 women of whom 556 (37%) had histologically-confirmed CIN (cervical intraepithelial neoplasia) 2 or 3 that included 114 HPV33 positive women with methylation measured for three L2 CpGs 5557, 5560 and 5566. Discrimination performance was assessed for the new classifier S5, built by adding HPV33 to the earlier classifier. RESULTS: HPV33 methylation measurement improved prediction among HPV33 positive women. Receiver operating characteristic analyses showed an area under the curve (AUC) for HPV33 methylation of 0.68 (95% CI 0.57-0.78). The earlier risk score was significantly improved by HPV33 methytlation (AUC = 0.82 vs 0.80; P < 0.001). For 90% sensitivity the specificity for CIN2/3 was 49% (95% CI 46-52%). CONCLUSIONS: Measurement of HPV33 DNA methylation contributes independent diagnostic information to EPB41L3 and HPV16, HPV18 and HPV31, and is superior to genotyping. Other HPV and human methylation target regions might be useful to further improve S5.

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.

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.