Primary High-risk Human Papillomavirus Testing Research Articles

Cervical Cancer Screening: Patient Perspectives on Transitioning to Primary High-Risk Human Papillomavirus Testing Alone.

In 2018, the US Preventive Services Task Force updated cervical cancer screening recommendations to allow for screening every 5 years with primary human papillomavirus (HPV) testing in combination with cytology (cotesting) or every 5 years with primary HPV screening alone. Despite these changes, the uptake of primary HPV screening has been lower than expected. The purpose of this study was to evaluate the patient perspective of an integrated health system transition from cotesting to primary HPV testing among a 30- to 65-year-old cohort. Semistructured phone interviews were conducted from July to December 2023 at Kaiser Permanente Colorado with 16 members aged 30-65 years. Interviews asked about reactions to the forthcoming change in cervical cancer screening, personal concern about cervical cancer risk, feedback on patient-facing education materials, and preference on communication timing and modality. Participants reported concerns about cervical cancer screening intervals, primarily the reduction in frequency leading to underdiagnosis of sexually transmitted infections (STIs). Participants recommended defining the rationale for the change to primary HPV testing in the patient education materials. Participants preferred communication about the change in-clinic between practitioner and patient. The interviews identified key themes, including the differentiation between cervical cancer and STI screening methodologies, potential underdiagnosis of STI and cervical cancer, and the rationale supporting primary HPV testing and associated screening intervals. These qualitative findings can inform health systems of potential patient concerns to address when considering the transition from cotesting every 3 years to primary HPV testing every 5 years for cervical cancer screening.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Self-Collection for Primary HPV Testing: Perspectives on Implementation From Federally Qualified Health Centers.

Primary testing for high-risk human papillomavirus (HPV) by self-collection could result in higher rates of cervical cancer screening. Federally qualified health centers (FQHCs) in the US serve a large proportion of women who have low income and no health insurance and are medically underserved - risk factors for being insufficiently screened for cervical cancer. Although the implementation of self-collection for HPV testing is not yet widespread, health care entities need to prepare for its eventual approval by the US Food and Drug Administration. We conducted focus groups and interviews among clinical and administrative staff and leadership to gather data on key logistical concerns that must be addressed before implementing self-collection for HPV testing in FQHCs. We identified focus group and interview participants from 6 FQHCs in North Carolina. We conducted focus groups with clinical and administrative staff (N = 45) and semistructured interviews with chief executive officers, senior-level administrators, chief medical officers, and clinical data managers (N = 24). Transcripts were coded by using codebooks derived from research questions and notes taken during data collection. Themes emerged on implementation of self-collection for HPV testing. We applied the constructs from the Consolidated Framework for Implementation Research (CFIR) to themes to identify domains of potential barriers and facilitators to implementation. Clinical personnel reported that offering self-collection for HPV testing is acceptable and feasible and can increase cervical cancer screening rates. Uncertainties emerged about accuracy of results, workflow disruptions, financial implications, and effects on clinic quality measures. Implementing self-collection for HPV testing was considered feasible and acceptable by participants. However, important health service delivery considerations, including financial implications, must be addressed before integrating self-collection for HPV testing into the standard of care.

Screening Tests and Support in Positive Human Papilloma Virus Tests

Screening for the detection of Cervical Cancer (CC) is moving from cytology or Papanicolaou (Pap) test to the detection of the primary highrisk Human Papillomavirus (HPV) test, based on evidence for this change, with support or triage options for positive HPV test results with better access innovations. The test of higher specificity such as cytology makes it an option for triage in positive HPV tests; but cytology and genotyping have been recommended for all positive HPV tests, especially for the other pool-positive hr-HPVs; but HPV-16/18 negative. Screening with primary HPV testing has been shown to be effective, affordable, and acceptable to women, especially in emerging countries; the use of Dual Staining (DS) to classify positive HPV results has higher sensitivity and specificity than HPV-16/18 genotyping or cytology at triage.

Cervical Cancer Screening in South Florida Veteran Population, 2014 to 2020: Cytology and High-Risk Human Papillomavirus Correlation and Epidemiology.

ObjectiveThis project aims to use our robust women's health patient data to analyze the correlation between cytology and high-risk human papillomavirus (Hr-HPV) testing, study the performance of Hr-HPV testing for detecting cytology lesions, and examine epidemiologic measures of human papillomavirus (HPV) infections in the women's veteran population.MethodsWe collected patient data from 2014 to 2020 from our computerized patient record system. We performed HPV assays using the cobas® 4800 system (Roche Diagnostics, Basel, Switzerland). The cobas HPV assay detects HPV 16, HPV 18, and 12 other HPV types (31, 33, 35, 39, 45, 51, 56, 58, 59, 66, and 68). We organized cytology results and Hr-HPV assays with Microsoft Access and Microsoft Excel (Microsoft Corporation, Washington, USA) for analysis.ResultsA total of 9437 cervical specimens were co-tested. High-grade cytology lesions - high-grade intraepithelial lesion (HSIL) or higher and atypical squamous cells, cannot exclude HSIL (ASC-H) - were overwhelmingly positive for Hr-HPV (94.1% and 87.2%, respectively). Low-grade cytology lesions - low-grade squamous intraepithelial lesion ((LSIL) and atypical squamous cells of undetermined significance (ASC-US) - were positive for Hr-HPV in lower percentages (72.6% and 54.9%, respectively). Hr-HPV testing had a sensitivity of 91.3%, a specificity of 93.1%, a positive predictive value of 16.4%, and a negative predictive value of 99.8% for detecting high-grade cytology lesions. Hr-HPV testing had a lower performance for detecting low-grade cytology lesions. Ten cases had high-grade cytology and negative Hr-HPV test. Out of 10 such patients, nine showed no dysplasia (six) or low-grade dysplasia (three) on subsequent biopsy. Overall, 14.4% of tests were positive for Hr-HPV. The highest positive Hr-HPV test rates were in the third and eighth decades of life, 25.1% and 22.0%, respectively. However, the eighth decade consisted of a small sample of only 50 women. In women over 30 years of age with Hr-HPV infections, HPV types 16 and 18 were present in 11.7% and 6.4% of tests, respectively. Other HPV types were present in 82.3% of tests.ConclusionsHr-HPV testing has a high performance in detecting high-grade cytology lesions and a lower performance for detecting low-grade cytology lesions. However, studies show that LSIL rarely progresses to cervical intraepithelial neoplasia grade 3 or higher (CIN3+), suggesting minimal to no impact on cervical cancer screening. We believe our findings are in accordance with recent studies and affirm the guidelines that recommend primary Hr-HPV testing as the preferred screening method. The percentage of positive Hr-HPV tests and rates for age and HPV types 16 and 18 in our women’s veteran population suggest similar HPV prevalence to that of the general US population.

Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening in the United States: Is It Time?

- The most recent update to cervical cancer screening guidelines offers interim guidance on the use of primary human papillomavirus (HPV) screening, with algorithms for management of results. After decades of screening with pure cytology and a shorter time with adjunctive HPV or cotesting with Papanicolaou (Pap) test and HPV, this is a significant change to our screening methods. - To briefly review the history of cervical cancer screening, the evidence upon which these interim guidelines were based, the arguments for and against primary HPV testing, and the current state of the field. - Primary studies, review articles, and commentaries were reviewed. - While there is evidence both for and against primary HPV testing, there are a growing number of countries adopting the practice. It would be worthwhile to be informed and prepared for such a change in the United States as well.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk HPV (hrHPV) testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Self‐sampling of vaginal fluid and high‐risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening

To study the value of self-sampling of vaginal fluid at home in combination with high-risk human papillomavirus (HPV) testing in a cohort of older women not attending Papanicolaou (Pap) smear screening. Women (n = 3618), aged 50-65 years, who had not attended screening for at least 6 years were offered self-sampling of vaginal fluid at home (study cohort). The collected material was analysed for the presence of high-risk HPV (using Hybrid capture 2; Hc2). Women with a positive HPV test were referred for colposcopy. These results were compared with the results of Pap smear screening in a corresponding age group of women (controls). The end point of the study was identification of a histological cervical intraepithelial neoplasia stage 2 (CIN2) and above (CIN2+). In all, 39.4% (n = 1426) women participated and 4.6% (n = 66) were high-risk HPV positive. Of the HPV-positive women 56 chose to attend a surgery (84.8%) after a mean time of 2.1 months and ten of these women (17.9%) showed CIN2+, corresponding to 0.70% of all participating women. In the controls, who participated in organised Pap smear screening, the prevalence of CIN2+ was 0.25% (15/6048). The odds ratio for identification of CIN2+ in women aged 50 years or older performing self-sampling and HPV test in comparison with Pap smear was: 2.84 (95% CI 1.14-6.77, P = 0.0174). In older women primary high-risk HPV testing (Hc2) and Pap smear screening showed equal specificity of around 96%. Self-sampling of vaginal fluid in combination with high-risk HPV testing appears to be an attractive method to improve screening coverage and decrease the prevalence of cervical cancer in women aged 50 years or older.

Optimizing technology for cervical cancer screening in high-resource settings.

Although historically successful in reducing the burden of cervical cancer, Papanicolaou (Pap) testing faces numerous limitations. A growing body of evidence suggests that modern screening practice will benefit from primary screening for high-risk human papillomavirus (HPV) infection, the causative agent of cervical cancer. Molecular tests detecting the presence of HPV nucleic acids consistently demonstrate high sensitivity relative to Pap testing, and provide reliable, dichotomous results. Pap cytology is ideally suited to triage HPV-positive cases owing to its high test specificity, and the accuracy of cytological readings will be maximized in high-prevalence conditions. This algorithm of primary HPV testing with Pap triage has been shown to maintain the high sensitivity of HPV testing without compromising Pap cytology's strong ability to rule out falsely positive diagnoses. Given the anticipated decline of high-risk HPV-16 and -18 infections in the emergent post-HPV vaccination era, highly sensitive primary HPV testing is especially warranted. Novel screening technologies that identify HPV viral gene expression continue to emerge and seek to complement current HPV testing by identifying those women who may be at risk of progressive disease. How to best incorporate these new technologies into clinical practice presents our next great challenge. Implementation of novel algorithms for cervical screening is not a trivial task. Avoidance of exceedingly complex screening algorithms is an important priority.