Need for expanded HPV genotyping for cervical screening.
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ABSTRACT:
SUBMITTER: Cuzick J
PROVIDER: S-EPMC5886893 | biostudies-other | 2016 Dec
REPOSITORIES: biostudies-other
Publications
Need for expanded HPV genotyping for cervical screening.
Cuzick Jack J Wheeler Cosette C
Papillomavirus research (Amsterdam, Netherlands) 20160601
The focus for HPV genotyping has largely been on types 16 and 18, based on their high prevalence in cervix cancer. However screening is focussed on the detection of high grade precursor lesions (CIN3 and CIN2), where other types have a greater role. While HPV16 retains its high predictive value in this context, HPV31 and especially HPV33 emerge as important types with higher positive predictive values (PPVs) than HPV18. Additionally full typing indicates that types 39, 56, 59 and 68 have much lo ...[more]
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Project description:In the last decade, the detection of human papillomaviruses (HPV) has become increasingly important in cervical cancer screening and the treatment of cancer precursors. HPV screening is recommended for the further evaluation of abnormal Pap tests or during follow-up after treating precancerous lesions. Several randomised controlled studies have shown that screening for cervical cancer using HPV detection can be more effective than cytology alone. Genotyping of different high-risk HPV (hrHPV) types obtained from smear tests has not yet gained widespread acceptance in clinical practice. However, significant differences have been noted in the oncogenicity of hrHPV genotypes. HPV 16 is by far the most common and oncogenic genotype. Genotyping of hrHPV could be helpful for the risk stratification of HPV-positive women.
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Project description:BackgroundPrimary high-risk human papillomavirus (hr-HPV) testing of self-collected cervico-vaginal swabs could increase cervical cancer screening coverage, although triage strategies are needed to reduce unnecessary colposcopies. We evaluated the use of extended hr-HPV genotyping of self-collected samples for cervical cancer screening.MethodsWe recruited women ages 25-65 years at two colposcopy clinics in North Carolina between November 2016 and January 2019, and obtained self-collected cervico-vaginal samples, provider-collected cervical samples, and cervical biopsies from all enrolled women. Self- and provider-collected samples were tested for 14 hr-HPV genotypes using the Onclarity Assay (Becton Dickinson). We calculated hr-HPV genotype-specific prevalence and assessed agreement between results in self- and provider-collected samples. We ranked the hr-HPV genotypes according to their positive predictive value (PPV) for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN2+).ResultsA total of 314 women participated (median age, 36 years); 85 women (27%) had CIN2+. More women tested positive for any hr-HPV on self-collected (76%) than on provider-collected samples (70%; P = 0.009) with type-specific agreement ranging from substantial to almost perfect. HPV-16 was the most common genotype in self-collected (27%) and provider-collected samples (20%), and HPV-16 prevalence was higher in self- than provider-collected samples (P < 0.001). In self- and provider-collected samples, HPV-16 had the highest PPV for CIN2+ detection.ConclusionsOverall sensitivity for CIN2+ detection was similar for both sample types, but the higher HPV-16 prevalence in self-collected samples could result in increased colposcopy referral rates.ImpactAdditional molecular markers might be helpful to improve the triage of women who are hr-HPV positive on self-collected samples.
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Project description:Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30-69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method.
| S-EPMC10046888 | biostudies-literature
Project description:BackgroundSelf-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women.MethodsA total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + .ResultsA total of 2731 HPCN women aged 30-64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; 'HPV16+ or HPV33/58/31/35+&p16+'; 'HPV16/33+ or HPV58/31/35+&p16+'; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the 'HPV16/33+' strategy: p16+; 'HPV16+ or HPV33/58/31/35 + &p16+'; HPV16/18/31/33/45/52/58 + &p16 + .ConclusionsGenotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.
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Project description:AimsTo devise nested multiplex polymerase chain reaction (NMPCR) protocol for detection of mucosal human papilloma viruses (HPVs) and typing of HPV-16 and -18 in formalin-fixed, paraffin-embedded (FFPE) tissues of carcinoma cervix (CaCx).Settings and designCross-sectional observational study.Materials and methodsNMPCR was done for simultaneous detection of HPV, targeting 134 bp L1 capsid gene employing GP+/mGP+ primers and typing of genotypes-16 and -18, targeting E6/E7 gene from 34 FFPE tissue blocks of CaCx and cervical intraepithelial neoplasia (CIN). Detection of 142 bp consensus sequence of L1 capsid gene was performed by nested PCR employing MY/GP+ primers. Sequencing of selected PCR amplicons of the later protocol obtained from control cell line DNA and 5 select samples were done for validation of the NMPCR protocol.Statistical analysis usedCalculation of percentage from the Microsoft Excel Software.ResultsOf 26 FFPE samples of CaCx, 17 (65.3%) samples were found positive for HPV by NMPCR. Amplicons of 142 bp L1 capsid gene employing MY/GP+ primers were observed in 11 (42.3%) samples of CaCx. Nearly 25% samples of CIN were positive for HPV. On sequence analysis, it was observed that the sample typed as HPV-16 by NMPCR was found to be the same on sequencing of amplicons obtained after MY/GP+ nested PCR.ConclusionsThis study indicates the usefulness of our NMPCR protocol for detection of mucosal HPVs and typing of HPV-16 and -18 from FFPE tissue samples of CaCx. The NMPCR protocol may be used to detect HPV and type common genotypes-16 and -18 in fresh tissue of cervical biopsy or scrape samples for screening of CaCx.
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Project description:BackgroundThe cobas HPV Test ("cobas"; Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for (i) atypical squamous cells of undetermined significance (ASC-US) triage to determine need for colposcopy, (ii) combined screening with cytology ("cotesting"), and (iii) primary HPV screening.MethodsTo assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared with those of an established method, the Linear Array HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+.ResultsGrouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the κ statistic for agreement between cobas and LA was 0.86 [95% confidence interval (CI), 0.86-0.87]. In all three scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women ages 21 and older with ASC-US (14.5%; 95% CI, 13.5%-15.5% vs. 3.5%; 95% CI, 3.3-3.6); women ages 30 years and older that were HPV-positive cytology-negative (10.3%; 95% CI, 9.6-11.1 vs. 2.3%; 95% CI, 2.2-2.4); and all women 25 years and older that were HPV-positive (18.5%; 95% CI, 17.8-19.2 vs. 4.3%; 95% CI, 4.2-4.4).ConclusionThe cobas and LA results show excellent agreement. The data support HPV16 typing.ImpactHPV16 typing is useful in the management of HPV-positive/cytology-negative women in cotesting, of all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US. Cancer Epidemiol Biomarkers Prev; 24(9); 1304-10.
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Project description:BackgroundWHO has recommended HPV testing for cervical screening where it is practical and affordable. If used, it is important to both clarify and implement the clinical management of positive results. We estimated the performance in Lusaka, Zambia of a novel screening/triage approach combining HPV typing with visual assessment assisted by a deep-learning approach called automated visual evaluation (AVE).MethodsIn this well-established cervical cancer screening program nested inside public sector primary care health facilities, experienced nurses examined women with high-quality digital cameras; the magnified illuminated images permit inspection of the surface morphology of the cervix and expert telemedicine quality assurance. Emphasizing sensitive criteria to avoid missing precancer/cancer, ~ 25% of women screen positive, reflecting partly the high HIV prevalence. Visual screen-positive women are treated in the same visit by trained nurses using either ablation (~ 60%) or LLETZ excision, or referred for LLETZ or more extensive surgery as needed. We added research elements (which did not influence clinical care) including collection of HPV specimens for testing and typing with BD Onclarity™ with a five channel output (HPV16, HPV18/45, HPV31/33/52/58, HPV35/39/51/56/59/66/68, human DNA control), and collection of triplicate cervical images with a Samsung Galaxy J8 smartphone camera™ that were analyzed using AVE, an AI-based algorithm pre-trained on a large NCI cervical image archive. The four HPV groups and three AVE classes were crossed to create a 12-level risk scale, ranking participants in order of predicted risk of precancer. We evaluated the risk scale and assessed how well it predicted the observed diagnosis of precancer/cancer.ResultsHPV type, AVE classification, and the 12-level risk scale all were strongly associated with degree of histologic outcome. The AVE classification showed good reproducibility between replicates, and added finer predictive accuracy to each HPV type group. Women living with HIV had higher prevalence of precancer/cancer; the HPV-AVE risk categories strongly predicted diagnostic findings in these women as well.ConclusionsThese results support the theoretical efficacy of HPV-AVE-based risk estimation for cervical screening. If HPV testing can be made affordable, cost-effective and point of care, this risk-based approach could be one management option for HPV-positive women.
| S-EPMC10580629 | biostudies-literature
Project description:Currently, clinical data for primary HPV screening alone are lacking in China. Here, we evaluate cervical cancer screening with primary HPV genotyping, as well as possible future screening strategy. Overall, high-risk HPV (hrHPV) prevalence was 18.2% among hospital-based population in Taizhou area. For cervical intraepithelial neoplasia 2 or worse (CIN2+), the sensitivity of primary hrHPV genotyping strategy and current cervical cancer screening strategy were 93.5%, and 71.1%, respectively; whereas the specificity was 17.5%, and 62.4%, respectively. Current cervical screening strategy had slightly higher positive predictive values (28.4%) for CIN2+ than hrHPV genotyping strategy (21.9%), whereas primary hrHPV genotyping strategy demonstrated higher negative predictive values (94.7%) than current cervical screening strategy (91.1%). Compared to HPV35/39/45/51/56/59/66/68 genotypes, the odds ratios (OR) for CIN2+ in HPV16/18/31/33/52/58 infection women were 3.2 (95% confidence interval [CI] 2.3-4.1). Primary hrHPV genotyping strategy provides a better predictive value than HPV16/18 genotyping alone in guiding the clinical management of the current cervical cancer screening. HPV testing without adjunctive cytology may be sufficiently sensitive for primary cervical cancer screening.
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Project description:BackgroundAccording to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples.MethodsFor each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test.ResultsHPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population.ConclusionsHPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.
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Project description:PurposeTo compare human papillomavirus genotype-specific performance of two genotyping assays, Anyplex II HPV28 (Seegene) and EuroArray HPV (EuroImmun), with Linear Array HPV (Roche).MethodsDNA extracted from clinican-collected cervical brush specimens in PreservCyt medium (Hologic), from 403 women undergoing management for detected cytological abnormalities, was tested on the three assays. Genotype-specific agreement were assessed by Cohen's kappa statistic and Fisher's z-test of significance between proportions.ResultsAgreement between Linear Array and the other 2 assays was substantial to almost perfect (κ = 0.60 - 1.00) for most genotypes, and was almost perfect (κ = 0.81 - 0.98) for almost all high-risk genotypes. Linear Array overall detected most genotypes more frequently, however this was only statistically significant for HPV51 (EuroArray; p = 0.0497), HPV52 (Anyplex II; p = 0.039) and HPV61 (Anyplex II; p=0.047). EuroArray detected signficantly more HPV26 (p = 0.002) and Anyplex II detected more HPV42 (p = 0.035) than Linear Array. Each assay performed differently for HPV68 detection: EuroArray and LA were in moderate to substantial agreement with Anyplex II (κ = 0.46 and 0.62, respectively), but were in poor disagreement with each other (κ = -0.01).ConclusionsEuroArray and Anyplex II had similar sensitivity to Linear Array for most high-risk genotypes, with slightly lower sensitivity for HPV 51 or 52.
| S-EPMC5883236 | biostudies-literature