Primary Cervical Cancer Screening Research Articles

Self-Collection for Primary HPV Testing: Acceptability in a Large Urban Emergency Department

Overdue cervical cancer screening increases the risk of invasive cervical cancer. It is important to identify settings where self-collection for primary human papillomavirus (HPV) testing can be implemented to have high effect on cervical cancer screening among hard-to-reach women with overdue screening. Herein, we examined the acceptability of HPV self-collection, including completion rates, attitudes, and experiences among women seeking noncritical care at a high-volume urban safety-net hospital emergency department (ED) in Houston, Texas, United States. In this single-arm intervention pilot study, we recruited women overdue for cervical cancer screening in the waiting areas of a safety-net hospital ED, seeking noncritical care from November 2023 to April 2024. Participants completed a preintervention survey and were offered an HPV self-collection kit. A postintervention survey followed immediately after HPV self-collection. Nearly 30% (119 of 401) screened for eligibility were overdue for cervical cancer screening. Of these, 93% were enrolled and were predominantly Hispanic, non-US born, and uninsured, with a median age of 45 years (IQR: 37 to 53). HPV self-collection completion rate was 90% (95% CI 82.9% to 94.9%). More than a quarter (27%) of these women had never been screened, and 14% had a screening >10 years prior. Most women who completed the HPV self-collection had positive attitudes and experiences and reported that the kit was easy to use (97%) and would be very willing to use HPV self-collection for regular screening (88%). HPV self-collection for primary cervical cancer screening during noncritical ED visits is possible and highly acceptable among women overdue for cervical cancer screening.

General practitioners may improve cervical screening equality in France

BackgroundVulnerable social groups have greater difficulty in accessing care and a lower quality of care. Health systems focused on primary care appear to be more effective, efficient and equitable. However, difficulties in accessing primary care are persisting. We focused on primary care screening for cervical cancer through Cervico-Uterine Smear (CUS), which has been shown to be effective in reducing disease incidence and mortality. In this study, we aimed to investigate the characteristics of women who undergo CUS according to the category of health professionals (general practitioners or gynaecologists) performing CUS and to analyse potential differences in access to care in terms of socioeconomic and geographical characteristics.MethodsThis was a retrospective observational study based on data from the main health insurance schemes in France, allowing analysis of health care consumption according to socioeconomic levels and proximity to health care services. We included women aged 25 to 64 years in 2012 for whom CUS would be a relevant procedure (695,694). The sociodemographic and territorial indicators were age, geographical area deprivation, and the availability of gynaecological care. The analysis was performed using multinomial logistic regression.ResultsA total of 202,271 (29%) patients underwent CUS; of whom 68% underwent CUS administered by gynaecologists and 28% were administered by general practitioners (GPs). However, inequalities in CUS screening rates were observed, with a decrease in the number of CUSs performed with increased age, a rural location, deprivation, and sparse health care provisions. Deprived people seemed less penalised by GPs.ConclusionsInvolvement of General Practitioners may improve cervical screening equality in France. The organisation of health systems around primary care may allow a better access to care and to account for the specific needs of deprived populations.

B-353 High risk HPV genotypes prevalence in Mexico

Abstract Background The greatest risk factor for the development of cervical cancer is infection by human papillomavirus (HPV). To date, more than 200 genotypes have been described, 14 of them considered by the WHO as high risk genotypes (HR) due to their high oncogenic capacity, with special attention given to genotypes 16 and 18. In Mexico, cervical cancer is the third cause of cancer-associated death in women, therefore, the timely detection of HR genotypes in women becomes imperative for the reduction of the burden of this disease. The detection of high-risk HPV genotypes through the PCR molecular test is part of primary cervical cancer screening, however, this practice is not common in Mexico. Here, we analyzed the results of HPV genotyping studies in women attending cervical cancer screening studies at Salud Digna with the objective of determining the prevalence and dsitribution of HR-HPV in Mexico. Methods Retrospective analysis of the results obtained for the detection of HPV in cervical samples from patients who were attended at Salud Digna clinics from june to august 2023. The samples were processed by automated RT-PCR (ROCHE COBAS PRIME-Cobas 6800). The kit used was the COBASHPV which detects the 14 HR genotypes and generates 4 types of results: negative, positive for HPV16, positive for HPV18 and positive for POOL (which includes the remaining 12 genotypes). For the analysis, Mexico was divided into 7 regions which share sociocultural factors (Northwest, North, West, Center, Gulf, South, Southeast). Results The study population was 95,934 patients (mean age of 41y). At the national level, 18.93% (18,159) of patients are positive for HPV POOL, 3.54% (3,399) for HPV 16 and 1.78% (1709) for HPV 18. The regions with the highest positivity are the southeast region for HPV POOL (22.32%), the south region for HPV 16 (3.77%) and HPV 18 (2.44%) while the region with the lowest percentage is the Northwest region (HPV POOL 17.86%, HPV16 3.39%, HPV18 1.57%). The age range with the highest percentage of positivity is 14-29y for HPV POOL, 30-39y for HPV 16, and 30-39y for HPV 18. Conclusions We found that Mexican patients are becoming infected at an early age with the genotypes that are part of the pool, however, we observe a marked trend towards a decrease in cases as the age of the population advances.The regions of the country with a higher percentage of HPV positive patients are the south and the southeast, regions that also concentrate most of the extreme poverty in Mexico. These numbers should be taken with caution given that in absolute values these are also are the regions of the country where the least people go for a cervical cancer screening study, emphasizing the need to promote these studies in these regions. In the case of genotypes with a greater oncogenic capacity, both HPV16 and HPV18 show a greater prevalence in economically productive age ranges. Retrospective studies like provide information that allow governments to generate public policies focused on the most affected regions.

Prevalence and Description of High-Grade Intraepithelial Lesions of Cervical Mucosa Cells in a Screening Programme for Cervical Cancer in Isère, France.

This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears. In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis.

Cost-Effectiveness of Computer-Assisted Cytology in a Primary hrHPV-Based Cervical Cancer Screening Programme.

Computer-assisted screening (CAS) shows equal performance compared to manual screening, although results are heterogeneous. Furthermore, using CAS may save costs through a potentially increased screening productivity of technicians, therefore also offering a solution for temporary and structural capacity shortage. We evaluated the circumstances under which CAS will be cost-effective compared to manual cytology triage in a primary HPV-based cervical screening programme. Microsimulation model MISCAN-Cervix was used to evaluate 198 different CAS scenarios with varying probabilities to detect cervical intraepithelial neoplasia grade 1 (CIN1) and CIN3 and cost reductions per test, compared to manual cytology triage. Cost-effectiveness was evaluated by costs per (quality-adjusted) life year ((QA)LY) gained. CAS will be cost-effective in all scenarios, except for the following combinations: (1) no cost reduction and an increased probability of detecting CIN1, (2) a cost reduction of €2 per test and an increased probability of detecting CIN1 from 4% onwards or (3) a cost reduction of €4 per test and an increased probability of detecting CIN1 from 6% onwards, compared to manual cytology triage. All CAS scenarios with any reduction in the probability of detecting CIN1 (i.e., increased CIN2+ specificity), or a reduction in costs from €6 per test onwards suggested a more cost-effective strategy compared to manual cytology triage. As we based our analysis on a realistic range in costs and test performance, the implementation of CAS is likely to be cost-effective. Our results can be used as a guideline to advise when to choose CAS instead of manual cytology triage.

Performance of visual inspection, partial genotyping, and their combination for the triage of women living with HIV who are screen positive for human papillomavirus: Results from the AIMA-CC ANRS 12375 multicentric screening study.

The WHO recommends the use of human papillomavirus (HPV) testing for primary cervical cancer (CC) screening because of its high sensitivity. However, triage is desirable to correctly identify HPV+ women who have high-grade lesions (CIN2+) and require treatment. The ANRS-12375 study was conducted in Côte d'Ivoire, Burkina Faso and Cambodia to assess the performance, feasibility and benefits of different triage options for detecting CIN2+ lesions: partial (HPV16 and HPV16/18/45) and extended genotyping, visual inspection (VIA) alone and VIA combined with partial genotyping. VIA was performed by gynecologists. The sensitivity, specificity, and diagnostic likelihood ratio (DLR) of each triage option for detecting CIN2+ lesions with histology as a reference standard were calculated. Of the 2253 women living with HIV (WLHIV) included, 932 (41%) were HPV+. A CIN2+ lesion was identified in 105 (13%) of the 777 participants with histopathology results. The sensitivity of VIA as a triage test for CIN2+ patients was 89%, while that for extended genotyping was 89%, that for HPV16/18/45 partial genotyping was 51%, and that for HPV16 partial genotyping was 36%. The specificities for these tests were 45%, 29%, 72%., and 85%, respectively. Combining VIA and/or partial genotyping positivity slightly increased the sensitivity (94%) at the cost of lower specificity (28%). There was significant intersite heterogeneity (p = .04). Among the three triage tests with a sensitivity ≥85%, the VIA had the highest specificity and positive likelihood ratio (p < .001). VIA and extended genotyping, whether independent or combined, are good triage options with high sensitivity for identifying WLHIV needing treatment for CIN2+.

Clinically validated HPV assays offer comparable long-term safety in primary cervical cancer screening: A 9-year follow-up of a population-based screening cohort.

Molecular testing for human papillomaviruses (HPV) is gradually replacing cytology in cervical cancer screening. In this longitudinal population-based cohort study, 4140 women 20 to 64 years old attending organized screening were tested at baseline by five different screening methods and followed for 9 years. To assess long-term safety, the cumulative risks of CIN2+/CIN3+ were estimated after a negative baseline result obtained by conventional cytology and four clinically validated HPV assays: Hybrid Capture 2 (hc2), RealTime High Risk HPV assay (RealTime), cobas 4800 HPV Test (cobas_4800), and Alinity m HR HPV (Alinity). HPV-negative women at baseline had a substantially lower risk for CIN2+ compared to those with normal baseline cytology: 0.84% (95% CI, 0.46-1.22), 0.90% (95% CI, 0.51-1.29), 0.78% (95% CI, 0.42-1.15), and 0.75% (95% CI, 0.39-1.11) for hc2, RealTime, cobas_4800, and Alinity, respectively, compared to 2.46% (95% CI, 1.88-3.03) for cytology. No differences were observed between HPV assays in longitudinal sensitivity (range: 86.21%-90.36%) and negative predictive values (range: 99.54%-99.70%) for CIN2+ in women ≥30 years, but were significantly different from cytology (p < .05). The 9-year cumulative risk of CIN2+ differed significantly between HPV genotypes, reaching 32.1% (95% CI, 14.5-46.1) for HPV16, 24.9% (95% CI, 4.7-40.8) for HPV18/45, 27.2% (95% CI, 14.6-37.8) for HPV31/33/35/52/58, and 8.1% (95% CI, 0.0-16.7) for HPV39/51/56/59. Four clinically validated HPV assays showed comparable safety and better assurance against precancerous lesions than cytology, but some important differences were identified in the performance characteristics of HPV assays impacting the referral rate. Information about the HPV genotype is valuable for guiding further clinical action in HPV-based screening programs.

Comparison of the ScreenFire and Xpert HPV assays for the detection of human papillomavirus and cervical precancer among women living with HIV in Malawi

BackgroundThe World Health Organization recommends human papillomavirus (HPV) testing for primary cervical cancer screening, including among women living with HIV (WLWH). Low-and-middle-income countries account for 85% of the cervical cancer burden globally, yet have limited access to HPV-based screening, largely due to cost. This study aims to compare the performance of a rapid, isothermal amplification HPV assay (ScreenFire) to that of the Xpert HPV assay for the detection of HPV and cervical precancer among WLWH in Malawi.MethodsWe utilized stored self- and provider-collected specimens from a prospective cohort study of WLWH in Malawi from July 2020 to February 2022. Specimens were tested with both Xpert and ScreenFire HPV assays. The overall and within-channel non-hierarchical agreement between ScreenFire and Xpert was determined for both self- and provider-collected specimens. Hierarchical ScreenFire HPV positivity by channel was compared to Xpert for each histological diagnosis—cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to <CIN2.Results315 matched self- and provider-collected specimens had valid results from both Xpert and ScreenFire testing and were included in analyses, of which 279 and 36 were HPV positive and HPV negative, respectively, on Xpert self-collection. Of the 315, 245 (78%) had normal pathology, 21 CIN1 (7%), 14 CIN2 (4%), and 35 CIN3 (11%). Of the 245 with normal pathology, 213 (87%) and 188 (77%) were HPV-positive on Xpert and ScreenFire self-collected specimens, respectively. Among provider-collected specimens, the assays had 80% agreement on overall HPV positivity (unweighted kappa 0.59, 95% 0.50–0.69). ScreenFire was HPV-positive in 90% of self-collected specimens that were HPV-positive on Xpert. Channel agreement between the assays was high for both self- and provider-collected specimens, but slightly lower for HPV18/45. In hierarchical analysis, ScreenFire demonstrated high concordance with Xpert testing for detecting CIN2+ cases in all channels, missing no HPV 16 or HPV 18/45 positive CIN2+ case that was positive on Xpert, in both self- and provider-collected specimens.ConclusionIn this study of stored specimens, the ScreenFire HPV assay performed well in the detection of HPV and CIN2+ among WLWH compared to the Xpert HPV assay. If supported by larger validation studies, ScreenFire could be an affordable alternative point-of-care HPV assay for use in LMICs.

Acceptability of self-collected vaginal samples for human papillomavirus testing for primary cervical cancer screening: comparison of face-to-face and online recruitment modes

BackgroundThis study aimed to assess the acceptability and attitudes of women towards human papillomavirus (HPV) self-sampling and compare the effectiveness of two delivery modes utilising face-to-face and online website for cervical cancer screening in Hong Kong.MethodsWomen aged 30–65 years were invited to participate by distributing the study information pamphlets at the specialist clinics of a regional acute hospital. Those who were interested in participating were given the option to join directly face-to-face or through an online website. All participants provided informed consent and received self-sampling kits and acceptability questionnaires either immediately (face-to-face) or through the post after registering at the website (online). All participants were requested to collect their own vaginal samples using a swab which was then brushed on a DNA sample storage card and returned to the hospital either in person or by post. The self-collected samples were tested for high-risk HPV using the Sentis™ HPV assay, a validated isothermal nucleic acid amplification real-time fluorescent detection assay. The primary outcome was the uptake rate of HPV self-sampling.ResultsOf the 1998 women recruited (1200 face-to-face, 798 online), 1377 returned their samples, giving an overall uptake rate of 68.9%. The uptake rate was significantly greater in the face-to-face mode than in the online mode (74.6% vs. 60.4%, p < 0.001). The median age of the participants was 49 years, 43.7% were never or under-screened, and 7.1% had high-risk HPV detected. Overall, 82.1% of the participants reported self-sampling convenient, and 79.3% were not embarrassed when collecting self-samples. However, only 49.8% were confident that they had collected the self-samples correctly. Most (91.1%) of the participants expressed willingness to perform self-sampling again, mostly because it was simple (79.2%) and quick (56.3%).ConclusionsHPV self-sampling can serve as an alternative primary screening method for cervical cancer in Hong Kong, especially for individuals who have not been adequately screened in the past. Both face-to-face and online website recruitment were associated with high acceptability, emphasising the potential benefits of utilising different platforms and strategies for reaching diverse populations.

Clinical Validation of the Vitro HPV Screening Assay for Its Use in Primary Cervical Cancer Screening.

Many scientific societies have issued guidelines to introduce population-based cervical cancer screening with HPV testing. The Vitro HPV Screening assay is a fully automatic multiplex real-time PCR test targeting the L1 GP5+/GP6+ region of HPV genome. The assay detects 14 high risk (HR) HPV genotypes, identifying individual HPV16 and HPV18 genotypes, and the HPV-positive samples for the other 12 HR HPV types are subsequently genotyped with the HPV Direct Flow Chip test. Following international guidelines, the aim of this study was to validate the clinical accuracy of the Vitro HPV Screening test on ThinPrep-collected samples for its use as primary cervical cancer screening, using as comparator the validated cobas® 4800 HPV test. The non-inferiority analysis showed that the clinical sensitivity and specificity of the Vitro HPV Screening assay for a diagnosis of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were not inferior to those of cobas® 4800 HPV (p = 0.0049 and p < 0.001 respectively). The assay has demonstrated a high intra- and inter-laboratory reproducibility, also among the individual genotypes. The Vitro HPV Screening assay is valid for cervical cancer screening and it provides genotyping information on HPV-positive samples without further sample processing in a fully automated workflow.

Should we use risk selection tests for HPV 16 and/or 18 positive cases: Comparison of p16/Ki67 and cytology.

Major screening abnormalities in precolposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primaryhuman papillomavirus (HPV)-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Among 30 066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available high-risk types ofHPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher positive predictive valuefor HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p < 0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2.26/2.19 vs. 3.54). Only oneHSIL+ case was missed in both triage models with DS incorporation. p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.

Prevalence and significance of HPV DNA detection below the clinical threshold of the commercial kit Alinity m HR-HPV assay (Abbott).

The positive clinical threshold of human papillomavirus(HPV) tests validated for primary cervical cancer screening (CCS) is designed to offer an optimal balance between clinical sensitivity and specificity. However, there may be a gap between the analytical sensitivity of the test and the positive clinical threshold, referred to here as the "gray-zone."This study aims to determine the prevalence and significance of HPV results obtained in the gray-zone in routine practice. Cervical samples obtained in our institution for CCS over a 22-month-period were tested with the Alinity m HR-HPV Assay (Abbott). Clinical and biological data, including cytological results and patients' HPV history were collected. Of the 6101 samples collected, 1.7% had an HPV result in the gray-zone (102 patients). The proportion of gray-zone results varied according to HPV genotype, reaching 11.8% of samples with detectable HPV DNA in the case of HPV31/33/52/58 genotypes. Reflex cytologies showed no abnormalities or AtypicalSquamous Cells of Undetermined Significance results in 74.6% and 17.9% of cases, respectively. A previous or subsequent HPV-positive result with a (possibly) identical genotype was observed in 58% and 38% of cases, respectively. Two women with a history of persistent HPV detection had a CIN2+ lesion 1 year after the gray-zone result. In conclusion, the proportion of HPV results in the gray-zone varies according to genotype. No cytological abnormality is observed in the majority of cases, but a few rare patients with a history of persistent HPV infection should be closely monitored even if the HPV result is transiently located in the gray-zone.

Comparison of high-risk HPV detection by the AmpFire® HPV Screening 16/18/HR technique (Atila Biosystems) and the hybrid capture 2 test (Qiagen).

Detection of high-risk human papillomaviruses (hrHPV) is widely used at the first line of cervical cancer screening, requiring rigorous validation of the clinical performance of commercial kits designed for this indication. Performance of the AmpFire HPV Screening 16/18/HR test (AF, Atila Biosystems) and the Hybrid Capture 2 test (HC2, Qiagen) for detecting hrHPV was cross-compared in 200 cervical samples in our institution. The global percentage of agreement between the 2 techniques was 95.0% (95%CI 92-98%) with a Cohen's kappa coefficient of 0.85 (95%CI 0.75-0.94). Ten samples showed discordant results between the 2 techniques in both directions (5 HC2+/AF- and 5 HC2-/AF+). Among possible explanations for these discrepancies was the detection of HPV66 and HPV53 genotypes in two samples, since these genotypes are targeted by the Ampfire test but not by the HC2 test, as well as intrinsic differences in analytical performance to target specific genotypes. A high level of agreement was observed between the two techniques, which encourages further testing in order to definitively validate the use of the Ampfire kit for primary cervical cancer screening.

Primary Human Papillomavirus Test Uptake and Cervical Cancer Screening Trends in the Midwest, United States.

Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake. Assess cervical cancer screening rates over time, particularly primary HPV test uptake, among patients in a midwestern practice. Evaluate associations between sociodemographics and screening adherence. Cross-sectional study. Qualifying subjects and type of screening test used were identified by applying ICD-9, ICD-10, lab test, and CPT codes to the Unified Data Platform. Sociodemographics were found through the electronic health record. Primary HPV uptake represented <1% of annual screening from 1/2017 to 1/2022. On 1/1/2022, only 55% of 21 to 29 year old and 63% of 30 to 65 year old were up to date with screening among the studied population. For 21 to 29 year old, compared with White women, Black women were 28% less likely to be screened [RR = 0.72 (0.66-0.79)]. Compared with never-smokers, current smokers were 9% less likely to be screened [RR = 0.91 (0.87-0.96)], past smokers were 14% more likely [RR = 1.14 (1.09-1.2)]. Among 30 to 65 year old, compared with White women, Black women were 14% less likely to be screened [RR = 0.86 (0.81-0.9)]. Compared with never-smokers, current smokers were 21% less likely to be screened [RR = 0.79 (0.77-0.81)], past smokers were 6% less likely [RR = 0.94 (0.92-0.95)]. Jointly considering race, ethnicity, smoking status, Charlson score, and rurality, findings were similar for 21 to 29 year old; Black women were screened less than White women [RR = 0.73 (0.67-0.79)]; current smokers [RR = 0.9 (0.85-0.94)] and past smokers [RR = 1.12 (1.06-1.17)] were screened less than never smokers. For 30 to 65 year old, Black women were screened less than White women [RR = 0.83 (0.79-0.88)]; current smokers [RR = 0.8 (0.78-0.81)] and past smokers [RR = 0.95 (0.93-0.96)] were screened less than never smokers. Screening rates remained below the Healthy People 2030 goal of 79.2% over time, particularly for younger Black women and current smokers, with minimal use of primary HPV screening.

Allplex HPV HR Detection assay fulfils all clinical performance and reproducibility validation requirements for primary cervical cancer screening

Human papillomavirus (HPV)-based screening offers better protection against cervical cancer compared to cytology, but HPV screening assays must adhere to validation requirements of the international guidelines to ensure optimal performance. Allplex HPV HR Detection (Allplex) assay, launched in the late 2022, is a fully automated real-time PCR-based assay utilizing innovative technology that enables quantification and concurrent distinction of 14 high-risk HPV genotypes (HPV16,18,31,33,35,39,45,51,52,56,58,59,66 and 68). We assessed the validity of the Allplex for cervical cancer screening purposes, via comparison to a clinically validated comparator assay (Hybrid Capture 2; HC2), and through assessment of intra-laboratory reproducibility and inter-laboratory agreement. A clinical validation panel comprised of 973 residual ThinPrep samples was obtained from women aged 30-64 years participating in the organized Slovenian screening program, of these 863 were from women undergoing their regular screening visit after a previous negative screen test while 110 were from women with underlying cervical intraepithelial neoplasia grade 2 or worse (CIN2+) lesions. The Allplex's relative clinical sensitivity for detection of CIN2+ and CIN3+ were 1.01 (95%CI;0.98-1.04) and 0.98 (95%CI;0.95-1.02), compared to that of HC2. At recommended thresholds of ≥98% and ≥90%, the Allplex's clinical sensitivity and specificity (p=0.0004 and p=0.02, respectively) were non-inferior to HC2. High intra-laboratory reproducibility and inter-laboratory agreement, both overall (98.1% and 97.9%, respectively) and at genotype level (>98.7%) was observed. In addition, analytical genotype-specific performance of Allplex was compared to that of its predecessor Anyplex HPV HR; high overall agreement was observed (96.3%; kappa value 0.88), with some variations in performance. In conclusion, Allplex met all validation criteria described in the international guidelines on sensitivity, specificity and laboratory reproducibility and can be considered clinically validated for primary cervical cancer screening.

Age-specific performance of human papillomavirus E6/E7 mRNA assay versus cytology for primary cervical cancer screening and triage: community-based screening in China.

In the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach. Between April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts. Our investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%-8.0% range, and were highest in 45-54-year olds. When compared with 35-44-or 45-54-year olds, HPV prevalence was highest in 55-64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35-44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7-100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3-82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45-54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55-64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7-100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0-80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771-0.920] vs. 0.812 [95% CI: 0.734-0.891], P = 0.236). Primary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35-44 and 55-64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35-44 year old females.

Epidemiology Characteristics and Potential Cervical Cancer Screening Value of Vulvar Human Papillomavirus in Chinese Women: A Multicenter Cross-Sectional Study.

Noninvasive self-sampling is a convenient option that may be highly accepted by women for home-based detection, which could increase the screening rate for cervical cancer (CC) and reduce its incidence and mortality. To compare the distribution of high-risk human papillomavirus (hr-HPV) between the vulva and cervix and to explore the clinical value of vulvar HPV detection in CC screening. The study was nested within a clinical trial on a recombinant HPV 9-valent vaccine for women ages 20 to 45 years. Women with paired vulvar and cervical specimens were included and underwent cytology and HPV detection. The consistency of HPV detection between vulvar and cervical specimens was evaluated using Cohen κ statistics. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the diagnostic accuracy of primary CC screening. The primary end points were cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+). A total of 7999 women were enrolled, and 83/33 cases were diagnosed as CIN2+/CIN3+. The HPV-positive rate in vulvar specimens (1785 of 7999; 22.32%) was higher than that in cervical specimens (1390 of 7999; 17.38%), and there were no significant differences in the distribution of hr-HPV genotypes between the vulva and cervix in patients with CIN2+/CIN3+. Vulva-based HPV primary screening showed sensitivity, specificity, PPV, and NPV comparable to those for cervix-based HPV primary CC screening in the detection of CIN3+. The distribution of vulvar and cervical HPV was similar in patients with CIN2+/CIN3+. Vulva-based HPV primary CC screening had acceptable diagnostic efficacy and might be used as a modality for primary CC screening.

Efficacy of Cobas HPV testing for predicting grade 2+ cervical intraepithelial neoplasia in a cancer prevention center and a gynecologic oncology clinic: A single-institution experience.

To evaluate the efficacy of Cobas human papillomavirus (HPV) testing to predict cervical intraepithelial neoplasia of grade 2 or higher (CIN2+), Cobas HPV testing results were correlated with follow-up biopsy in patients from Cancer Prevention Center (CPC) and Gynecologic Oncology Clinic (GOC) of The University of Texas MD Anderson Cancer Center. Institutional data for patients who underwent Cobas HPV and Papanicolaou (Pap) cytology cotesting from 2019 to 2020 were retrospectively reviewed. Surgical follow-up results were compared with Cobas HPV testing results in two populations. A total of 2226 patients, including 921 women (mean age, 55.2years) seen at the CPC and 1305 women (mean age, 49.3years) seen at the GOC, were included. Specimens from GOC patients had a significantly higher HPV positivity rate than did those from CPC patients (22.9% vs. 10.1%; p<.001). Cobas HPV testing was positive in all seven CPC patients with surgical follow-up results showing CIN2+. Among 36 GOC patients with CIN2+ lesions, five patients had HPV-/Pap+testing results. Although only seven CPC patients had CIN2+, Cobas HPV testing showed 100% sensitivity for predicting CIN2+ in this group. Sensitivity for CIN2+ was 86.5% in the GOC group, whereas 13.9% of GOC patients with CIN2+ had negative HPV testing results. Cobas HPV testing was highly efficacious for predicting CIN2+ lesions in the low-risk CPC population, which supports HPV primary screening for cervical cancer in low-risk populations. For high-risk patients, especially those with a history of CIN2+/cervical cancer, HPV/Pap cotesting may still be necessary to maintain a high clinical sensitivity for CIN2+.

Comparing the Costs and Diagnostic Outcomes of Replacing Cytology with the QIAsure DNA Methylation Test as a Triage within HPV Primary Cervical Cancer Screening in The Netherlands.

Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure® FAM19A4/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort (n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC.

OP81 Cost Effectiveness Of Human Papillomavirus Extended Genotyping For Cervical Cancer Screening In Singapore

IntroductionThe World Health Organization recommends the human papillomavirus (HPV) test for cervical cancer screening. HPV partial genotyping (PGT) identifies HPV16 and HPV18 individually and the 12 other high-risk HPV genotypes (hrHPV) collectively. In contrast, HPV extended genotyping (XGT) identifies six hrHPV individually (HPV16,18,31,45,51, and 52) and the other eight in three groups (HPV33/58, HPV56/59/66, and HPV35/39/68). XGT allows better risk stratification for patient management and monitoring of persistent same-genotype infections (PSGI), which convey a higher risk for cervical cancer. This study compared the cost, quality-adjusted life-years (QALYs), and resource use of XGT with PGT when used as the primary cervical cancer screening method in Singapore.MethodsA discretely integrated condition event simulation was developed for screening 500,122 women aged 30 to 69 years over five years from the health system perspective, using a three percent annual discount. For XGT, women with HPV35/39/51/56/59/66/68 and reflex cytology of atypical squamous cells of undetermined significance were recalled for a repeat screening in one year, instead of the immediate colposcopy referral that occurs with PGT. At repeat screening, colposcopy was only provided for women with PSGI on XGT. Published data from Singapore were used for inputs and supplemented with data from international literature. Deterministic and probabilistic uncertainty analyses were conducted. Scenario analysis was conducted to simulate various HPV burdens among women. XGT was cost effective when the incremental cost-effectiveness ratio (ICER) relative to PGT was below SGD100,000 (USD118,906) (gross domestic product per capita in 2021).ResultsXGT was cost effective relative to PGT (ICER SGD16,370 [USD19,465]), with fewer colposcopies (n=7,130; 19%), liquid-based cytology tests (n=6,027; 7%), and clinic consultations (n=9,787; 2%) but more HPV tests (n=2,446; 0.5%). The ICER was most sensitive to the relative cost of XGT and the cost of PGT. XGT remained cost effective in one-way sensitivity analysis in all 1,000 probabilistic uncertainty simulations and in scenario analysis with various HPV burdens.ConclusionsXGT can provide a cost effective, risk-based approach to primary cervical cancer screening, with lower resource utilization than PGT.