High-risk Human Papillomavirus Testing Research Articles

The vaginal microbiota among the different status of human papillomavirus infection and bacterial vaginosis.

Although human papillomavirus (HPV) infection plays a decisive role in causing tumors, its infection is insufficient for independently promoting cancer development and other co-factors facilitate the carcinogenic process. The objective of this study was to demonstrate the association between vaginal microbiota and high-risk human papillomavirus (HR-HPV) infection in women with and without bacterial vaginosis (BV). The study included 1015 women aged 21-64 who participated in cervical cancer screening in two areas of China from 2018 to 2019. Women were collected cervical exfoliated cell specimens and reproductive tract secretions samples for HR-HPV, BV and microbial composition testing. From the non-BV& HPV- group (414 HPV-negative women without BV) to the non-BV& HPV+group (108 HPV-positive women without BV), to the BV& HPV-group (330 HPV-negative women with BV) and then to the BV& HPV+group (163 HPV positive-women with BV), microbial diversity increased. The relative abundance of 12 genera, including Gardnerella, Prevotella, and Sneathia increased, while Lactobacillus declined. Correlation networks of these genera and host characteristics were disrupted in the non-BV& HPV+group, and the network trended more disordered in the BV& HPV+group. Besides, multiple HPV infection, certain HPV genotype infection and cervical intraepithelial neoplasia (CIN) status were associated with some microbes and higher microbial diversity. HPV shifted the composition and diversity of vaginal microbiota, and BV further reinforced the trend. The relative abundance of 12 genera increased and 1 genus decreased on account of BV and HPV infection, and some genera including Lactobacillus, Prevotella, and Sneathia were associated with some specific HPV genotypes infection and CIN.

Promoter hypermethylation analysis of host genes in cervical intraepithelial neoplasia and cervical cancers on histological cervical specimens

BackgroundDNA methylation is an essential factor in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer. The aim was to investigate the diagnostic value provided by methylation biomarkers of six tumor suppressor genes (ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671) for cervical precancerous lesions and cervical cancer.MethodsThe histological cervical specimens of 396 cases including 93 CIN1, 99 CIN2, 93 CIN3 and 111 cervical cancers were tested for methylation-specific PCR assay (GynTect®) of score and positive rate. Among them, 66 CIN1, 93 CIN2, 87 CIN3 and 72 cervical cancers were further used for paired analysis. A chi-square test was used to analyze the difference of methylation score and positive rate in cervical specimens. The paired t-test and paired chi-square test were for analyzing the methylation score and positive rate in paired CIN and cervical cancer cases. The specificity, sensitivity, odds ratio (OR) and 95% confidence interval (95% CI) of the GynTect® assay for CIN2 or worse (CIN2 +) and CIN3 or worse (CIN3 +) were evaluated.ResultsAccording to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P = 0.000). The methylation score above 1.1 was more common in CIN2 + than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P = 0.033, 0.000 and 0.000, respectively), except for CIN2 (P = 0.171). While the positive rate of GynTect® in each paired group had no difference (all P > 0.05). The positive rate of every methylation marker in the GynTect® assay showed differences in four cervical lesion groups (all P < 0.05). The specificity of GynTect® assay for detection of CIN2 + /CIN3 + were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect®/ZNF671 were significantly higher in CIN2 + : odds ratio (OR) 5.271/OR 13.909, and in CIN3 + : OR 11.022/OR 39.150, (all P < 0.001).ConclusionThe promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect® assay based on cervical specimens provides diagnostic values for detecting CIN2 + and CIN3 + .

High sensitivity and specificity rates of cobas® HPV test as a primary screening test for cervical intraepithelial lesions in a real-world setting.

Cervical carcinoma (CC) is the fourth most common malignancy among women. Screening with Papanicolau smear is linked to a reduction in CC incidence rates when screening programs have been developed. However, this technique has several limitations, including moderate sensitivity rates for detection of cervical preneoplastic HPV-related lesions. In this real-world study, we proposed to evaluate the sensitivity and specificity rates of cobas® test, which amplifies target DNA fragments by polymerase chain reaction and hybridization of nucleic acids for the detection of 14 HR-HPV types in a single analysis) used as primary screening test for CC and preneoplastic lesions in women aged 25-65 years in a large University Hospital in Buenos Aires. A total of 1044 patients were included in the sample (median age: 46 years); sensitivity and specificity rates for the HR-HPV test used as primary screening test were 98.66% (95% confidence interval [95CI]: 97.67-99.3%) and 87.15% (95CI: 84.93-89.15%), respectively. The positive predictive value was 88.47% (95CI: 86.54%-90.42%) and the negative predictive value was 98.48% (95CI: 97.75%-99.23%). The cobas® HR-HPV testing was highly sensitive and specific for the detection of CC and preneoplastic lesions in real practice.

Prevaccination Prevalence of Type-Specific Human Papillomavirus Infection by Grade of Cervical Cytology in Estonia

Large-scale data on type-specific human papillomavirus (HPV) prevalence and disease burden worldwide are needed to guide cervical cancer prevention efforts. Promoting the research and application of health care big data has become a key factor in modern medical research. To examine the prevaccination prevalence of high-risk HPV (hrHPV) and type distribution by cervical cytology grade in Estonia. This cross-sectional study used text mining and the linking of data from electronic health records and health care claims to examine type-specific hrHPV positivity in Estonia from 2012 to 2019. Participants were women aged at least 18 years. Statistical analysis was performed from September 2021 to August 2022. Type-specific hrHPV positivity rate by cervical cytological grade. A total of 11 017 cases of cervical cytology complemented with data on hrHPV testing results between 2012 and 2019 from 66 451 women aged at least 18 years (mean [SD] age, 48.1 [21.0] years) were included. The most common hrHPV types were HPV16, 18, 31, 33, 51 and 52, which accounted for 73.8% of all hrHPV types detected. There was a marked decline in the positivity rate of hrHPV infection with increasing age, but the proportion did not vary significantly based on HPV type. Implementation of nonavalent prophylactic vaccination was estimated to reduce the number of women with high-grade cytology by 50.5% (95% CI, 47.4%-53.6%) and the number with low-grade cytology by 27.8% (95% CI, 26.3%-29.3%), giving an overall estimated reduction of 33.1% (95% CI, 31.7%-34.5%) in the number of women with precancerous cervical cytology findings. In this cross-sectional study, text mining and natural language processing techniques allowed the detection of precursors to cervical cancer based on data stored by the nationwide health system. These findings contribute to the literature on type-specific HPV distribution by cervical cytology grade and document that α-9 phylogenetic group HPV types 16, 31, 33, 52 and α-7 phylogenetic group HPV 18 are the most frequently detected in normal-to-high-grade precancerous lesions in Estonia.

Time trends in prevalence of p16 positivity and combined HPV/p16 positivity in a large cohort of Danish vulvar cancer patients.

Vulvar cancer is rare, but causes substantial morbidity in affected patients. A subset of vulvar cancers is caused by high-risk human papillomavirus (hrHPV), which primarily exerts its oncogenic effect through upregulation of tumor suppressor protein p16. Tumors positive for both hrHPV and p16 (double positive) are assumed to be HPV-driven, but only few large studies have investigated the combined prevalence of hrHPV and p16 positivity in vulvar cancer over time. In this Danish cross-sectional study, we assessed the prevalence of p16 positivity and double positivity for hrHPV and p16 in a large sample of vulvar squamous cell carcinomas (VSCCs) diagnosed during 1990 to 2017. In a nationwide register, we identified VSCCs from 13 hospitals across Denmark, and collected archival tumor tissue for hrHPV testing with INNO-LiPA and immunohistochemical p16 staining. We calculated the prevalence of hrHPV, p16 positivity and double positivity according to time, age and histological subtype and evaluated time trends through estimated annual percentage changes. We included 1278 VSCCs. Overall, 35.0% (95% confidence interval [CI]: 32.4-37.6) were positive for p16 and 31.0% (95% CI: 28.4-33.5) were positive for both hrHPV and p16. The prevalence of p16 positivity and double positivity increased over time, both in women aged ≤59 and ≥60 years. The double positive prevalence was higher in nonkeratinizing (60.7%) and warty/basaloid VSCCs (67.5%) than in keratinizing (16.1%) and verrucous VSCCs (5.0%). These results indicate that approximately one-third of vulvar cancers were caused by hrHPV infection, supporting a substantial preventive potential of the HPV vaccine.

Risk Analysis Stratification of CIN 2+ Development in a Cohort of Women Living with HIV with Negative Pap Smear and HR-HPV Test during a Long-Term Follow-Up.

Women living with Human Immunodeficiency Virus are at higher risk of cervical cancer and precancer compared to women without HIV infection. The aim of the study is to evaluate the risk factors for the development of CIN2+ in a cohort of WLWH with negative colposcopy and cytology during a long follow-up period. We enrolled, in a multicentric retrospective cohort study, WLWH who attended the colposcopic services from 1999 to 2019. Patients with a normal Pap smear, a negative HR-HPV test, and at least one year of follow-up were considered for the anlysis. The five-year cumulative incidence of histologically confirmed HSIL was 8.3% (95% CI = 2.6-13.6) among subjects with a CD4+ cell count of <200 cells/µL at any visit and 2.1% (95% CI = 0.7-3.4, p = 0.001) in women with a CD4+ cell count of persistently >200 cells/µL. In women with persistent HR-HPV infection, the five-year cumulative incidence of CIN 2+ was 6% (95% CI = 1.6-10.2) versus 2% (95% CI = 0.4-3.6, p = 0.012) in women without HPV infection. An HIV viremia of >200 copies/mL, a CD4+ cell count of <200 cells/µL, persistent HR-HPV infection, and smoking ≥10 cigarettes/day were all independent and statistically significant risk factors associated with the development of CIN2+ during follow-up. WLWH with good immune status and negative Pap smear and HR-HPV test have a low risk for CIN2+.

Feasibility and acceptability of self-collection of Human Papillomavirus samples for primary cervical cancer screening on the Caribbean Coast of Nicaragua: A mixed-methods study.

Cervical cancer is the primary cause of cancer death for women in Nicaragua, despite being highly preventable through vaccination against high-risk genotypes of the Human Papillomavirus (hrHPV), screening for hrHPV, and early detection of lesions. Despite technological advances designed to increase access to screening in low resource settings, barriers to increasing population-level screening coverage persist. On the Caribbean Coast of Nicaragua, only 59% of women have received one lifetime screen, compared to 78.6% of eligible women living on the Pacific and in the Interior. In concordance with the WHO's call for best practices to eliminate cervical cancer, we explored the feasibility and acceptability of self-collection of samples for hrHPV testing on the Caribbean Coast of Nicaragua through a multi-year, bi-national, community-based mixed methods study. Between 2016 and 2019, focus groups (n=25), key informant interviews (n=12) [phase I] and an environmental scan [phase II] were conducted on the Caribbean Coast of Nicaragua in partnership and collaboration with long-term research partners at the University of Virginia and community-based organizations. In spring 2020, underscreened women on the Caribbean Coast of Nicaragua were recruited and screened for hrHPV, with the choice of clinician collection or self-collection of samples. Over the course of the study, providers and potential patients expressed significant acceptability of self-collection of samples as a strategy to reduce barriers currently contributing to the low rates of screening (phases I and II). Ultimately 99.16% (n=1,767) of women chose to self-collect samples, demonstrating a high level of acceptability of self-collection in this pilot sample (phase III). Similarly, focus groups, key informant interviews, and the environmental scan (phases I and II) of resources indicated critical considerations for feasibility of implementation of both HPV primary screening and subsequently, self-collection of samples. Through phase III, we piloted hrHPV screening (n=1,782), with a 19.25% hrHPV positivity rate. Self-collection of samples for hrHPV testing demonstrated high acceptability and feasibility. Through concerted effort at the local, regional, and national levels, this project supported capacity building in reporting, monitoring, and surveilling cervical cancer screening across the continuum of cervical cancer control.

Application Analysis of High Risk HPV Detection Combined with Cervical Cytology, Colposcopy and Pathology in Cervical Lesions of Women in Tiandeng County

Purpose: To understand the application of high-risk HPV detection combined with cervical cytology, colposcopy and pathology in cervical lesions of women in Tiandeng County. Method: Women in the outpatient and inpatient departments of our hospital from January 2021 to October 2022 were collected for high-risk HPV testing, TCT, colposcopy and pathological examination according to their personal wishes, to understand the application of relevant examinations in cervical lesions. Result: In 2021, the number of patients was 5801, among whom 1743 patients had received cervical cancer examination in the past, accounting for 30.05% of the total number of patients, and 5795 who had volunteered for TCT examination this time, accounting for 99.90% of the total; A total of 289 cases of atypical squamous cells with unclear significance (ASC-US) were detected, excluding 11 cases of high-grade squamous intraepithelial lesions (ASC-H), 122 cases of low-grade squamous intraepithelial lesions (LSIL), 16 cases of high-grade squamous intraepithelial lesions (HSIL), 2 cases of squamous cell carcinoma (SCC), and 4 cases of atypical adenocyte (AGC); Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of people who volunteered for high-risk HPV testing was 4237, and the number of positive cases was 740, accounting for 17.47% of the screening population; Among 740 HPV-positive patients, 488 high-risk HPV-positive patients were selected for TCT examination, and 87 patients were found to be TCT positive; From 401 high-risk HPV-positive and TCT negative patients, 287 patients with possible lesions were screened out for colposcopy; The results showed that 60 patients may have certain cervical lesions and need further pathological examination and the results showed that 28 patients had CTN1 and 18 patients had CIN2 - 3. In 2022, 8840 patients received medical treatment, among which 3188 patients had received cervical cancer examination in the past, accounting for 36.06% of the total number of patients, and 8314 patients voluntarily underwent TCT examination, accounting for 94.05% of the total number of patients. 434 cases of atypical squamous cells with ambiguous meaning (ASC-US) were detected, excluding 13 cases of high-grade squamous intraepithelial lesions (ASC-H), 217 cases of low-grade squamous intraepithelial lesions (LSIL), 35 cases of high-grade squamous intraepithelial lesions (HSIL), 1 case of squamous cell carcinoma, and 4 cases of atypical adenocarcinoma (AGC); Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of volunteers for high-risk HPV testing was 3871 cases, and the number of positive cases was 654 cases, accounting for 16.89% of the screening number. 527 high-risk HPV-positive patients were selected from 654 HPV-positive patients for TCT examination, and the number of TCT-positive patients was found to be 49. From 478 high-risk HPV-positive patients with TCT negative, 276 patients with possible lesions were screened out for colposcopy; The results showed that 66 patients may have certain cervical lesions and need further pathological examination; and then the results showed that 31 cases of CTN1 and 6 cases of CIN2 - 3. Conclusion: Gynecological high-risk HPV examination can provide better etiological sources for cervical cancer screening; Cervical cytology examination has high sensitivity; Colposcopy examination has high specificity; Pathological examination can be used as an effective supplement for cervical cytology examination and colposcopy; So high-risk HPV combined with cytology examination, colposcopy examination and pathological examination has high clinical application value; It is worth popularizing and applying.

Abstract A108: Improving communication and management following a positive home HPV self-sampling kit result

Abstract Background: Over 14,000 cervical cancers are diagnosed annually in the U.S. In 2019, ~30% of individuals with a cervix were under-screened based on current guidelines. Previous studies established feasibility of mailed self-sampling high-risk HPV test kits to improve screening adherence. Qualitative findings from our HOME trial found unmet information needs and anxiety among patients with a positive kit result. We designed the STEP trial to test optimized implementation strategies for educating patients about screening when offering the kit to patients due/overdue for screening, and when reporting results. Purpose: To evaluate acceptability of the implementation strategies, we interviewed individuals after receiving a positive kit result about the result communication processes and their information needs. Methods: The STEP trial added a centralized licensed practical nurse to communicate about and arrange scheduling for all patients with positive kit results, and provided an educational pamphlet to explain the purpose of HPV testing (especially difference to Pap testing) and how latent infections can reactivate. Telephone interviews were conducted from December 2021 to March 2022 with 29 patients (56% of invited) who had a positive kit result. Interview guide asked about reaction to the kit, results communication, patient-provider interactions, and follow-up visit experiences; and included a survey regarding attitudes toward the kit. Five coders analyzed interview transcripts using iterative content analysis; 12 transcripts were double-coded. Codes were organized into node reports to identify overarching themes. Results: Of 29 participants, most (65.5%) were non-Hispanic White and the average age was 47.5 years (SD=11.2). Participants appreciated the convenience of the kit, though a few worried about the accuracy of self-sampling test results, especially compared to screening performed by a provider. While surprised by the positive kit result, all reported feeling reassured after talking with the nurse and understood next steps in the diagnosis and management process, although some reported still wanting to check with their primary care provider about the test findings. Though an educational pamphlet was provided with the home HPV kit, most participants did not recall receiving it or using it to understand their kit results. After reflecting on home kit versus in-clinic screening, most (69%) preferred using the kit on their own to provider-collected screening. All (100%) agreed that the kit instructions were easy to understand, however 90% were sure that they had sampled the right place, and 86% believed that the home test results were correct. Discussion: Unlike the prior HOME trial, there was less negative affect expressed by patients after receiving results. This suggests patients received the information needed to continue with the screening process and supports the value of a centralized nurse. Providing educational materials at multiple timepoints may further improve results communication in the future. Citation Format: Meera Muthukrishnan, Jasmin A. Tiro, Kris Hansen, John Lin, Caitlin Dorsey, Hongyuan Gao, Catherine Troja, Melissa Anderson, Richard Meenan, Beverly B. Green, Diana S.M. Buist, Rachel Winer. Improving communication and management following a positive home HPV self-sampling kit result [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A108.

Aptima HR-HPV Testing of Cytology Specimens Is an Effective Supplement for p16 Staining to Improve Diagnostic Accuracy for HPV-Related Oropharyngeal Squamous Cell Carcinoma

Introduction: Regarding a small proportion of oropharyngeal squamous cell carcinoma (OPSCC) patients who tested p16-positive but human papillomavirus (HPV)-negative, we attempted to perform HPV testing to improve the accuracy of HPV detection in OPSCC patients. Methods: We simultaneously performed Aptima HPV testing of cytological specimens and p16 immunohistochemistry (IHC) staining of histologic biopsies from the same cohort of patients with head and neck SCC (HNSCC). The cytological specimens included fine-needle aspiration specimens from patients with enlarged nodes and endoscopic brushing specimens from the primary lesions of patients without enlarged nodes. Cases with discordant results for p16 IHC staining and Aptima HPV testing were reexamined by a third method, RNAscope testing. Results: Sixty patients with HNSCC (39 OPSCC and 21 non-OPSCC) were recruited for examination of HPV status. Among these patients, 28 were p16+/HPV+, 29 were p16−/HPV−, 2 were p16+/HPV−, and 1 was p16−/HPV+. The overall concordance rate between Aptima HPV testing and p16 IHC was 95.0%. Three cases with discordant results for these two methods were reexamined by RNAscope testing, and all were confirmed to be HPV negative. The prevalence of HPV in OPSCC and non-OPSCC patients was 61.5% (24/39) and 19.0% (4/21), respectively. The sensitivity and negative predictive values of Aptima HPV testing and p16 IHC were consistent at 100%, while the specificity and positive predictive values were 96.9% and 96.6% versus 93.8% and 93.3%, respectively. Additionally, 30 OPSCCs were simultaneously examined and diagnosed by both brush cytology and biopsy pathology; six of these SCCs were underdiagnosed by histopathology but accurately diagnosed by supplemental brush cytology. Conclusion: Aptima HPV testing of cytology specimens can be used as an adjuvant examination to identify false-positive OPSCC patients after p16 IHC of biopsies, while brush cytology may be a supplemental method for the histologic diagnosis of malignant oropharyngeal tumors.

High-risk HPV testing vs liquid-based cytology for cervical cancer screening among 25- to 30-year-old women: A historical cohort study.

High-risk human papilloma virus (hrHPV) DNA testing is more sensitive than cytology screening, achieving greater protection against cervical cancer. Controversy exists regarding the preferred screening method for women 25-30 years of age. At this age, infection with HPV is common and usually transient. Consequently, hrHPV screening in this age group is fraught with high false-positive screening results, leading to more colposcopies and unnecessary treatments with the potential for harm. In the present study, we aimed to compare the results of two screening methods in relation to high-grade cervical intraepithelial lesion detection rate in the young age group of 25-30 years. Retrospective information on cervical cytology, hrHPV testing, colposcopy referrals and histologic results, from one screening round, were retrieved from the Maccabi HealthCare Health Maintenance Organization centralized database during the study period from March 1, 2017 to April 1, 2019 for 25- to 30-year-old women. Screening with hrHPV testing for types 16, 18 and 12 other hrHPV types was compared with the conventional PAP liquid-based cytology (LBC) test. Odds ratio (OR) of detection with 95% confidence interval (CI) was calculated for cervical intraepithelial neoplasia (CIN) grade 3 or higher (CIN 3+). During the study period, 42 244 women 25-30 years old underwent cervical cancer screening; of them, 20 997 were screened with LBC between March 1, 2017 and March 1, 2018 and compared with 21 247 who were screened with hrHPV between April 1, 2018 and April 1, 2019. Testing for hrHPV resulted in a higher colposcopy referral rate compared with primary LBC screening: 9.8% vs 7.8%, respectively; (OR 1.28; 95% CI 1.2-1.37; p< 0.001). Screening with hrHPV led to significantly higher detection of CIN 3+ lesions (OR 1.4; 95% CI 1.2-1.6; p< 0.001) compared with LBC. HPV infections with non-16/18 hrHPV (other hrHPV) were the most prevalent (84.8%). In women 25-30 years old, primary hrHPV screening was associated with a higher detection rate of CIN 3+ compared with cytology screening and should be considered for primary screening in this age group.

Clinical implementation of a cervical cancer screening program via co-testing at a university hospital.

The Human Papillomavirus (HPV) test is a crucial technology for cervical cancer prevention because it enables programs to identify women with high-risk HPV infection who are at risk of developing cervical cancer. Current U.S. Preventive Services Task Force recommendations include cervical cancer screening every three years with cervical cytology alone or every five years with either high-risk HPV testing alone or high-risk HPV testing combined with cytology (co-testing). In Argentina, 7,548 new cervical cancer cases are diagnosed each year with 3,932 deaths attributed to this cause. Our study aims to show the clinical implementation of a cervical cancer screening program by concurrent HPV testing and cervical cytology (co-testing); and to evaluate the possible cervical cancer screening scenarios for Latin America, focusing on their performance and average cost. A cervical cancer screening five year program via co-testing algorithm (Hybrid-2-Capture/cytology) was performed on women aged 30-65 years old at a university hospital. Statistical analysis included a multinomial logistic regression, and two cancer screening classification alternatives were tested (cytology-reflex and HPV-reflex). A total of 2,273 women were included, 91.11% of the participants were double-negative, 2.55% double-positive, 5.90% positive-Hybrid-2-Capture-/negative-cytology, and 0.44% negative-Hybrid-2-Capture/positive-cytology. A thorough follow-up was performed in the positive-Hybrid-2-Capture group. Despite our efforts, 21 (10.93%) were lost, mainly because of changes on their health insurance coverage which excluded them from our screening algorithm. Of the 171 women with positive-Hybrid-2-Capture results and follow-up, 68 (39.77%) cleared the virus infection, 64 (37.43%) showed viral persistence, and 39 (22.81%) were adequately treated after detection via colposcopy/biopsy of histological HSIL (High-Grade Squamous Intraepithelial Lesion). The prevalence of high-risk HPV in this population was 192 women (8.45%), with HSIL histology detection rates of 17 per 1,000 screened women. A multinomial logistic regression analysis was performed over the women with positive-Hybrid-2-Capture considering the follow up (clearance, persistence and HSIL) as dependent variable, and the cytology test results (positive- or negative-cytology and Atypical Squamous Cells of Undetermined Significance, ASC-US) as independent variable. The model supported a direct association between cytology test results and follow up: negative-cytology/clearance, ASC-US/persistence, and positive-cytology/HSIL with the following probabilities of occurrence for these pairs 0.5, 0.647 and 0.647, respectively. Cytology could be considered a prognostic-factor in women with a positive-Hybrid-2-Capture. These findings suggest that the introduction of co-testing could diminish the burden of cervical cancer in low-and middle-income-countries, acting as a tool against inequity in healthcare.

Clinician practices, knowledge, and attitudes regarding primary human papillomavirus testing for cervical cancer screening: A mixed-methods study in Indiana

Primary human papillomavirus (HPV) testing, in which a high-risk HPV test is administered without cytology, was first included in 2018 US cervical cancer screening guidelines. Subsequent guidelines endorsed primary HPV testing as the preferred method for cervical cancer screening following evidence of its clinical and economic benefits, although many sources still indicate it as an option along with cytology and HPV/Pap co-testing. Primary HPV testing could be key to improving the declining cervical cancer screening rates in the US; however its adoption has been slow as clinicians are hesitant to make the change. Indiana ranks in the top ten states for cervical cancer mortality, with marked race-ethnic disparities in cervical cancer screening and low HPV vaccination rates. To examine clinician practices, knowledge, and attitudes regarding primary HPV testing, in 2021 we conducted an online cross-sectional survey (n = 224) and in-depth interviews (n = 20) with Indiana clinicians practicing cervical cancer screening. Only 3 % reported using primary HPV testing for eligible patients, and only 50 % were willing to adopt it as the preferred cervical cancer screening method for the recommended patient group. In a multivariable logistic regression model, knowledge of the effectiveness (aOR 2.58 [1.41–4.72]) and perceived benefit (aOR 7.35 [3.65–14.81]) of primary HPV testing predicted willingness to adopt. In-depth interviews revealed knowledge gaps, uncertainty, and perceived limitations of this method as the reasons for limited uptake of primary HPV testing. Targeted messages about the benefits and effectiveness may enhance clinician knowledge, acceptance, and adoption.

Urinary Bladder Squamous Cell Carcinoma In-Situ in a Background of Condyloma Acuminatum – A Diagnostic Challenge

Abstract Introduction/Objective Condyloma acuminatum is a rare lesion of the urinary bladder and urethra, usually associated with extensive anogenital condyloma acuminatum and immunosuppression. It is considered a risk factor for developing urinary bladder squamous cell carcinoma. Methods/Case Report We report a case of an 80-year-old male with a history of invasive squamous cell carcinoma of the anus, status-post chemoradiation ten years prior, and renal transplantation for end-stage renal disease 15 years prior. He presented with a lesion adjacent to the neoureteral orifice at the bladder dome. Biopsy revealed nonkeratinizing, hyperplastic papillary fronds of squamous epithelium with koilocytic change and viral atypia. The tumor was positive for p16, GATA3, and p40 and negative for high-risk and low-risk Human Papilloma Virus by in-situ hybridization. However, the morphology was consistent with squamous cell carcinoma in-situ arising in a background of condyloma acuminatum, which was concurred by an outside expert. Bladder condyloma acuminata are often challenging to recognize, given their extreme rarity and the possibility of negative low-risk and high-risk Human Papilloma Virus tests. Lack of prior history of anogenital condylomas can further obscure this diagnosis. Results (if a Case Study enter NA) NA. Conclusion This case raises awareness of condyloma acuminatum as a rare entity that needs to be considered in the differential diagnosis of bladder tumors, especially in immunosuppressed patients. Given that the treatment strategies for squamous cell carcinoma arising from condyloma acuminatum differ from that for urothelial carcinoma with squamous differentiation, distinguishing these lesions from one another is imperative.

Correlation Between hr-HPV Genotypes/Negative Cytology with Cervical Histology Findings

Abstract Introduction/Objective It is well established that the persistent of hr-HPV infection is necessary for the development of cervical dysplasia. Currently, routine cervical cancer screening include both high-risk human papilloma virus (hr- HPV) testing and cervical cytology tests. The guidelines for managing HPV-positive/cytology-negative results is cotesting at 1 year, and/or immediate colposcopy if HPV16 and/or HPV18 is positive. We analyzed the correlation between hr-HPV genotypes /negative cytology with cervical histology findings. Methods/Case Report Retrospective chart review was performed to identify all negative pap smears with positive hr-HPV and follow up colposcopy for patients who presented to our institution from January 2018 to December 2019. We calculated the distribution of HPV genotypes within low grade and high-grade cervical lesions among patients with HPV-positive/cytology-negative pap smears. Results (if a Case Study enter NA) 179 patients with HPV-positive/cytology-negative pap smears were included. The age range was 22-69 years old. Among these patients, 6.70% had low-grade squamous intraepithelial lesion (LGSIL) and 6.14% had high-grade squamous intraepithelial lesion (HSIL) on follow up biopsy. The detection rates of HPV genotypes among patients with LGSIL diagnosis were HPV16 (41.66%), HPV18 (16.66%) and other hr-HPV (41.66%). The detection rates of HPV genotypes among patients with HGSIL diagnosis were HPV16 (9.09), HPV18 (0%), other hr-HPV (72.72%), combined HPV16 + other hr-HPV (9.09), combined HPV18+ other hr-HPV (9.09%). Conclusion According to our data, patients with negative cytology and HGSIL on biopsy have higher association with other hr-HPV (not 16 or 18) than HPV 16 and 18. Patients with negative cytology and LGSIL on biopsy have higher association with HPV16 and other hr-HPV subtypes than HPV18. Thus, we recommend follow-up colposcopy even for patients with other hr-HPV infection.

High-Risk HPV Genotype Distribution According to Cervical Cytology and Age.

A retrospective study of a single laboratory's results from patients in the United States to investigate high-risk human papillomavirus (HPV) genotype distribution according to cervical cytology and age was performed. Anonymous results of 23 580 patients' cervical specimens sent to Medical Diagnostic Laboratories, LLC, for cervical cytology and HPV testing between August 2020 and August 2021 were analyzed. Overall, any of the 14 high-risk HPV genotypes identified were detected in 2302 of the 23 580 patients (9.8%), with HPV 52 (1.4%), HPV 39 (1.3%), HPV 51 (1.3%), and HPV 16 (1.2%) being the most frequent in all patients. Multiple high-risk HPV infection was observed in 1.3% of all patients. HPV 16 was most likely to be a single high-risk genotype detected as compared with detection with other high-risk HPV genotypes, in contrast to HPV 33, which is least likely to be a single high-risk genotype detected as compared with detection with other high-risk HPV genotypes. High-risk HPV detection was greatest in patients under 25 years old (<21-year-olds, 24.6%, and 21-25-year-olds, 25.4%). In patients with low-grade squamous intraepithelial lesions, the most frequently detected high-risk HPV genotypes were HPV 51 (10.5%) and HPV 39 (9.1%), and in patients with high-grade squamous intraepithelial lesions, the most frequently detected high-risk HPV genotypes were HPV 16 (25.6%) and HPV 52 (17.1%). HPV genotyping and cervical cytology data analysis may contribute to and inform cervical cancer screening and HPV vaccination programs.

Concurrent Cervical and Anal High-Risk Human Papillomavirus Infection in Women Living With HIV: An Observational Case-Control Study.

To evaluate the prevalence and correlates of concurrent uterine cervical and anal HR-HPV infections in women living with HIV (WLHIV). A cross-sectional study was undertaken at a tertiary care hospital and linked ART center. One hundred and forty-one WLHIV and 161 HIV-negative women were enrolled for cervical and anal cytology as well as HR-HPV testing using the HC2 method. Screen-positive women were followed-up with colposcopy/anoscopy and/or repeat cytology. Appropriate statistical tests were applied to assess the association of concurrent HR-HPV with various parameters. Concurrent cervical and anal HR-HPV infection was detected in 22 WLHIV (16.3%) and 5 HIV-negative women (3.1%), the difference being statistically significant ( P &lt; 0.001 ). Among WLHIV, concurrent HR-HPV was associated with tobacco use ( P &lt; 0.001 ), receptive anal intercourse ( P = 0.02 ), low CD4 counts ( P = 0.001 ), and negatively with ART intake ( P = 0.004 ) on bivariate analysis. Multivariate logistic regression analysis showed a positive association of concurrent HR-HPV positivity with tobacco use ( P = 0.02 ) and low nadir CD4 counts ( P = 0.03 ). WLHIV, especially those with CD4 counts less than 200/µL, should be offered HR-HPV screening and follow-up to detect cervical and anal lesions.

Prevalence of cervical high-risk human papillomavirus and cytological abnormalities in elderly Turkish women

Objective: Cervical cancer (CC) screening ends at the age of 65 in Turkey, as in many countries. However, about a quarter of CCs occurs in women over the age of 65. Persistent high-risk human papillomavirus(HR-HPV) infection is the most important factor leading to CC. In this study, we aimed to investigate the prevalence of cervical HR-HPV and cytological abnormalities in Turkish women aged 65 and over. Patients and Methods: A total of 467 women between the ages of 66-84 who were referred to the gynecology outpatient clinics for any reason between January 2010 and December 2021 were included in the study. Pap smears (liquid-based) of patients were screened for HPV DNA typing using the COBAS test system and evaluated cytopathologicaly. Results: The mean age of women was 72.4 years. The prevalence of HR – HPV was 5.1% (n = 24), HPV-16 and HPV-18 subtypes constituted 58.4% of all positive cases. The rate of cervical HR-HPV and cytological abnormalities were not statistically different between age groups. Of the women with a positive HR-HPV test in Pap smear, cytological abnormalities were found to be more frequent when compared to HR-HPV negatives (95.8%, n=23 vs 4.3%, n=19, p&amp;lt;0.00001). Conclusion: We demonstrated a strong correlation between HR-HPV positivity and cytological abnormality in the elderly women population. Age groups were not significantly different regarding the prevalence of HR-HPV and abnormal cytology. We also revealed that the prevalence of HR-HPV and cytological abnormalities in the elderly population were not high enough to explain the second peak of cervical cancer seen in older ages. More studies are needed to explain which testing methods should be used in the elderly patient population.

Prevalence of cervical human papillomavirus in Mexico, 2010-2017: analysis of 2.7 million women.

Prevalence of cervical high-risk human papillomavirus (hrHPV) infection varies greatly. Data on distribution of hrHPV infection constitute important evidence for decision-making when implementing HPV testing into cervical cancer screening programs. We estimate the prevalence of cervical hrHPV infection in a large sample of women in a middle-income country and explore variation by age, community marginalization and region in women using public cervical cancer screening services. Records covering 2010-2017 from a registry of hrHPV test results (Hybrid Capture 2 and polymerase chain reaction) in 2,737,022 women 35-64years were analyzed. In this observational study, 32 states were categorized into five geographical regions and classified by degree of marginalization. We stratified by test type and estimated crude and adjusted prevalence and rate ratios and used Poisson models and joinpoint regression analysis. Prevalence was higher in women 35-39years, at 10.4% (95% CI 10.3-10.5) and women 60-64years, at 10.1% (95% CI 10.0-10.3). Prevalence was higher in the southeast, at 10.5% (95% CI 10.4-10.6). Women living in less marginalized areas had a significantly higher prevalence, at 10.3% (95% CI 10.2-10.4) compared to those in highly marginalized areas, at 8.7% (95% CI 8.5-8.7). HPV16 infection was detected in 0.92% (2,293/23,854) of women and HPV18 infection was detected in 0.39% (978/23,854) of women. Understanding the distribution of HPV prevalence has value as evidence for developing policy in order to improve cervical cancer screening strategies. These results will constitute evidence to allow decision makers to better choose where to focus those resources that they do have.

Agreement between Xpert and AmpFire tests for high-risk human papillomavirus among HIV-positive women in Rwanda.

High-risk human papillomavirus (hrHPV) may cause more than 99% of cervical cancers worldwide. Little is known about performance differences in tests for hrHPV. This study analysed agreement for detection of hrHPV between the established, clinically validated Xpert HPV assay and the novel isothermal amplification-based AmpFire HPV genotyping assay. This study was nested in a larger project on cervical cancer screening among approximately 5000 women living with HIV in Kigali, Rwanda. This sub-study included 298 participants who underwent initial screening for cervical cancer using the Xpert HPV assay and visual inspection with acetic acid in 2017 and tested positive by either or both. Participants were rescreened using colposcopy, and cervical samples were collected between June 2018 and June 2019. Samples were then tested for HPV using the Xpert HPV assay and AmpFire HPV genotyping assay. Agreement between results from both tests was analysed using an exact version of McNemar test and chi-square test. Overall agreement and kappa value for detection of hrHPV by Xpert and AmpFire were 89% and 0.77 (95% confidence interval: 0.70-0.85). AmpFire was marginally more likely to diagnose hrHPV-positive than Xpert (p = 0.05), due primarily to the extra positivity for HPV16 (p < 0.001). Overall, there was good to excellent agreement between the Xpert and AmpFire when testing hrHPV types among women living with HIV. AmpFire was more likely to test extra cases of HPV16, the most carcinogenic HPV type, but the clinical meaning of detecting additional HPV16 infections remains unknown.