High-risk Human Papillomavirus Testing Research Articles

Abstract 2142: Spatial distribution of high-risk human papillomavirus (HR-HPV) across 23 Chicago community areas and correlates

Abstract Background: Despite availability of effective vaccines and screening, cervical cancer claimed 4,280 lives in 2022. We explored the spatial distribution of high-risk human papillomavirus (“HR-HPV”) infection across 23 Chicago Community Areas (CCAs) served by the University of Illinois Health Network (UI Health). Using a modified Warnecke et al Health Disparity Outcomes (HDO) model, we hypothesized that CCAs with higher rates of structural violence, the social, economic, and political systems exposing populations to risks and vulnerabilities, would correlate with increased HR-HPV. Methods: Electronic medical records of patients receiving routine cervical cancer screening between January 1, 2015 and December 31, 2019 were reviewed. As per the 2014 ACS guidelines. HR-HPV test results were captured as HR-HPV positive, HR-HPV-16, HR-HPV-18 and non-16/18 HR-HPV, the latter consisting of 12 HR-HPV subtypes. Structural violence variables were used from Chicago Health Atlas (2015-2019) with percent poverty, hardship index score, easy access to fruit and vegetables, routine checkup, homicide, and primary care provider across CCAS. Univariate Poisson regression was used to compare the associations between selected structural violence factors and HR-HPV prevalence. Univariate multinomial logistic regression evaluated associations between structural violence indicators and HR-HPV subtypes Global p-values were obtained using ANOVA at 0.05 significance. Results: 8,566 women met inclusion criteria out of 13,466 total women. 75% were Black or Hispanic. Overall prevalence of cervical HR-HPV infection was 20.3% (n=1,737), ranging from 8.7% to 27.2% across CCAs. Median age for women was 36. Percent with primary care provider was negatively associated with HPV infection (IRR = 0.99 with 95% CI (0.98, 1.00), adjusted p-value=0.023), indicating women living in CCAs with higher rates of primary care provider were less likely to have HR-HPV. Easy access to fruit and vegetables (adjusted p-value = 0.007) and percent with primary care provider (adjusted p-value = 0.009) were significantly associated with HR-HPV subtypes. Women living in CCAs with easy access to fruit and vegetables (OR = 0.99, with 95% CI (0.98,0.99)) as well as those with higher rates of primary care provider (OR = 0.98, with 95% CI (0.97,0.99)) were less likely to have non-16/18 HR-HPV. Conclusion: HR-HPV is the most common sexually transmitted infection, and most women clear the infection naturally. As the origin of 99% of cervical cancer, understanding the reasons HR-HPV persists and progresses to cancer among certain individuals and groups is critical. Novel interventions like increasing access to fruit and vegetables could compliment widely available and effective vaccines. Citation Format: Gelila Goba, Jiehuan Sun, Quetzal Class, Joel Schwartz, Sage Kim, Karriem Watson, Lisa Tussing-Hummphreys, Yamile Molina, Shannon MacLaughlan, Ziqiao Xu, Benjamin Aldred, Subhash Kumar Kolar Rajanna, Tamika Alexander, Anna-Barbara Moscicki. Spatial distribution of high-risk human papillomavirus (HR-HPV) across 23 Chicago community areas and correlates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2142.

Abstract 3942: Mailed at-home self-sampling for HPV testing increases screening participation among under-screened patients in a U.S. safety net health system: Results of the PRESTIS trial

Abstract Background: In global settings, self-sampling for human papillomavirus (HPV) testing is associated with a pooled 2-fold increase in cervical cancer screening participation over usual care among underscreened persons. The Prospective Evaluation of Self-Testing to Increase Screening (PRESTIS) Trial is the first pragmatic randomized controlled trial (RCT) in the U.S. to evaluate the effectiveness of mailed at-home self-sampling for HPV testing in a safety net health system setting. Safety net systems provide care to medically underserved individuals at elevated cervical cancer risk. We hypothesized that patients who were mailed a self-sampling kit would have greater screening participation compared with those receiving usual care; and that patient navigation, a patient-centered intervention to address barriers to care, would further increase participation. Methods: PRESTIS is a three-arm pragmatic RCT of n=2,270 patients in a U.S. safety net health system who are under-screened for cervical cancer (i.e., no Pap in 3.5 years or Pap/HPV co-test in 5.5 years). Eligible participants were identified through the electronic health record (EHR) and randomized to arms: 1) telephone recall to provider-performed screening (usual care); 2) telephone recall + mailed self-sampling kit for HPV testing; or 3) telephone recall + mailed self-sampling kit + telephone-based patient navigation. Self-sampled swabs were tested for high-risk (HR)-HPV. HR-HPV+ patients were navigated to clinical follow-up. The primary outcome, incidence of screening participation, was ascertained by EHR review at 6 months post-randomization and defined as return of a completed kit or attendance for provider-performed screening. Results: Participants were enrolled 02/2020-08/2023. Primary outcomes have been ascertained for n=2,115 participants. Participants were predominantly Hispanic/Latina (68.6%); 53.4% indicated Spanish as primary language; and 60.3% were uninsured. Mean age was 47.9 years (SD: 10.4 years); median time since last screening test was 9.5 years (range: 1.6-21.7 years). In intent-to-treat analyses, screening participation was 15.3% (95% CI 13.0% - 17.9%) in Arm 1; 44.0% (40.4% - 47.6%) in Arm 2; and 51.4% (47.7% - 55.0%) in Arm 3. Relative incidence of screening in Arms 2 and 3 versus Arm 1 was 2.90 (2.42 - 3.47) and 3.36 (2.82 - 4.01), respectively. Relative incidence of screening in Arm 3 versus Arm 2 was 1.16 (1.04 - 1.29). Conclusion: Compared with usual care, mailed at-home self-sampling increased screening participation among an under-screened population by almost three-fold when used alone and over 3.3-fold when combined with telephone-based patient navigation. After FDA approval, self-sampling for HR-HPV testing has the potential to dramatically increase participation in cervical cancer screening in underserved populations. Citation Format: Jane R. Montealegre, Elizabeth Y. Chiao, Matthew L. Anderson, Susan G. Hilsenbeck, Shaun Bulsara, Susan L. Parker, Maria Daheri, Trisha L. Amboree, Kathleen M. Schmeler, Maria L. Jibaja-Weiss, Mohammad Zare, Ashish A. Deshmukh, Michael E. Scheurer. Mailed at-home self-sampling for HPV testing increases screening participation among under-screened patients in a U.S. safety net health system: Results of the PRESTIS trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3942.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment-Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology.

The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan-Meier survival analysis with Logrank test were performed. Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47-26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.

Human Papilloma Virus Typing as a Triage Tool for Women with Postcoital Bleeding: A Retrospective Cohort Study.

Objective: To investigate the performance of human papilloma virus (HPV) typing as a triage tool in the management of patients with postcoital bleeding (PCB). Methods: All patients referred for colposcopy at a cervical pathology clinic of a nationwide health insurance organization, due to PCB and had a preceding high-risk HPV (hrHPV) test between 2018 and 2020, were retrospectively located. Demographic and pathologic data were collected from electronic medical files. Sensitivity, specificity, and negative and positive predictive value of hrHPV test according to final pathology were calculated. Results: Three hundred ninety patients referred for colposcopy due to PCB with a preceding hrHPV test were located. HrHPV-positive patients were significantly younger (33.7 ± 10 vs. 37.2 ± 9, p < 0.006) with a higher proportion of nulliparous, nonmarried, and smokers compared with hrHPV-negative patients (75% vs. 47%, p < 0.001; 75.4% vs. 45.1%, p < 0.001; and 24.6% vs. 12.8%, p < 0.028, respectively). No case of high-grade cervical intraepithelial neoplasia (CIN2/3) was identified among hrHPV-negative patients. The sensitivity and NPV of the hrHPV test for high-grade cervical lesions were both 100%, decreasing to 36% and 95%, respectively, for any cervical dysplasia (CIN1/CIN2/CIN3). Adding cytology to HPV typing had a negligible effect on test performance. At univariate analysis, age, HPV vaccine status, nulliparity, and positive HPV typing were independently associated with cervical dysplasia. At multivariate analysis, only positive HPV typing remained significantly associated with cervical dysplasia (hazard ratio 2.75, confidence interval 1.1-6.5, p = 0.023). Conclusion: A negative HPV test even in the presence of PCB may rule out cervical dysplasia with extremely high accuracy and may save unnecessary colposcopies.

Atypical squamous cells of undetermined significance cervical cytology in Bahrain: Reporting rates, high-risk HPV testing, and cytologic and histopathologic follow-up findings.

Atypical squamous cells of undetermined significance cytology (ASC-US) is a challenging and equivocal diagnosis for pathologists in cervical Pap smears. The data on ASC-US cervical cytology in Bahrain are deficient. This study reviewed and identified the reporting rates, high-risk human papillomavirus (HPV) testing results, histopathologic follow-up findings, and the cytologic progression of patients diagnosed with ASC-US in Bahrain. A retrospective chart review was conducted on the medical records of 23,888 women who had Pap smear test results between January 2019 and March 2022 at the main referral tertiary hospital in Bahrain to identify the ASC-US cases. High-risk HPV (hrHPV) genotype was identified, and the histopathological results of the cervical biopsy was recorded. In addition, cytologic follow-up Pap smear tests conducted within 1 year of ASC-US diagnosis were tracked to monitor the progression or regression of ASC-US. In this study, 259 out of 23,888 women reported to have ASC-UC cytology results with a reporting rate of 1.1%. The mean age of the ASC-US cases was 43 ± 11.6. Thirty percent of the ASC-US cases tested positive for hrHPV, and they were predominantly infected with the other hrHPV genotype (75%). When the histopathological changes of the cervix were analyzed, 82.1% had normal histopathologic findings. However, low-grade cervical intraepithelial neoplasia-1 was reported in 2 cases (7.1%), and high-grade cervical lesions (cervical intraepithelial neoplasia-2 and higher) were reported in 3 cases (10.7%). Regarding the cytologic follow-up, most of the ASC-US cases were negative for intraepithelial lesion or malignancy (NILM) (73.8%) or had persistent ASC-US (17.9%). The remaining minority of cases progressed into either low-grade squamous intraepithelial lesions (6%) or high-grade squamous intraepithelial lesions (2.4%). There was a statistically significant and relatively strong association between the cytology follow-up findings and the hrHPV test results (χ2 [2] = 8.869, P < 0.012, Cramer's V = 0.417). This is the first and largest study to characterize the ASC-US cytology cases in Bahrain. The reporting rates of ASC-US fell within the worldwide reported range. Although most of the ASC-US cases regressed into NILM, ASC-US showed progression into more advanced cervical cytologic diagnoses or contributed to the malignant transformation of cervical tissue, especially in the presence of hrHPV infection which was positive in 30% of the ASC-US cases. This emphasizes the role of cotesting (combination of hrHPV genotyping and Pap smear test) and the importance of colposcopic evaluation of those women with cytologic follow-up tests at 1 year of diagnosis. Implementing these recommendations in the cervical cancer screening practice in Bahrain will help in having a better management plan for women diagnosed with ASC-US cervical cytology.

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.

Exploratory Analysis of Concordance Between Clinician-Collected and Self-Sampled Human Papillomavirus Tests in a Small Cohort of Average- and High-Risk Patients.

Cervical cancer screening rates have stagnated, but self-sampling modalities have the potential to increase uptake. This study compares the test characteristics of self-sampled high-risk human papillomavirus (hrHPV) tests with clinician-collected hrHPV tests in average-risk (i.e., undergoing routine screening) and high-risk patients (i.e., receiving follow-up after abnormal screening results). In this cross-sectional study, a relatively small cohort of average-risk (n = 35) and high-risk (n = 12) participants completed both clinician-collected and self-sampled hrHPV testing, along with a brief phone survey. We assessed hrHPV positivity, concordance, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity across both methods (for types 16, 18, or other hrHPV). We also explored the relationship between test concordance and sociodemographic/behavioral factors. Among average-risk participants, hrHPV positivity was 6% for both test methods (i.e., hrHPV-positive cases: n = 2), resulting in reported concordance, PPV, NPV, sensitivity, and specificity of 100%. Among high-risk participants, hrHPV positivity was 100% for clinician-collected tests but only 67% for self-sampled tests, showing varied concordance and sensitivity. Concordance was not associated with sociodemographic or behavioral factors. Self-sampled hrHPV testing demonstrated high accuracy for average-risk patients in this exploratory study. However, its performance was less consistent in high-risk patients who had already received an abnormal screening result, which could be attributed to spontaneous viral clearance over time. The limited number of participants, particularly HPV-positive cases, suggests caution in interpreting these results. Further research with larger cohorts is necessary to validate these findings and to explore the integration of self-sampled hrHPV testing into routine clinical care, particularly for patients with a history of cervical abnormalities. NCT04591977, NCT04585243.

Value of high‑risk human papillomavirus detection combined with colposcopy in the diagnosis of cervical cancer and precancerous lesions.

In the present study, the diagnostic value of high risk-human papillomavirus (HR-HPV) combined with colposcopy for the detection of cervical cancer and precancerous lesions was evaluated. A total of 397 patients with confirmed cervical disease were enrolled between August 2020 and December 2021. According to the pathological diagnosis, the patients were divided into cervical intraepithelial neoplasia grade I (CIN I; n=153 cases), CIN II (n=101 cases), CIN III (n=86 cases) and cervical cancer (n=57 cases) groups. The HR-HPV-positive rate of the patients with different lesion types was compared, and the consistency of colposcopy and pathological examination results were assessed. For cervical cancer and precancerous lesions, the diagnostic value and efficacy of HR-HPV testing, colposcopy and combined HR-HPV testing and colposcopy examination were compared using pathological examination results as the gold standard. The results of the present study demonstrated that in patients with cervical cancer, the positive rate of HR-HPV (100.00%; n=57/57) was higher than that in patients with precancerous lesions, and the positive rate of HR-HPV in patients with CIN I type (36.60%, n=56/153) was lower than that in patients with CIN II (83.17%, n=84/101) and CIN III (82.56%, n=71/86) types (P<0.05). There was no significant difference in the HR-HPV-positive rate between patients with CIN II and CIN III (P>0.05). Cohen's κ coefficient for colposcopy examination and pathological examination of patients with cervical cancer and precancerous lesions was 0.622, the diagnostic accuracy was 90.43% (n=359/397), the positive predictive value was 65.57% (n=40/61), and the negative predictive value was 94.94% (n=319/336). Receiver operating characteristic curve analysis demonstrated that the area under the curve of the combined examination in the diagnosis of cervical cancer and precancerous lesions was 0.904, which was higher than that of colposcopy (0.820) or HR-HPV testing (0.802) alone (P<0.05). The results of the present study indicated that HR-HPV detection combined with colposcopy has diagnostic value for cervical cancer and precancerous lesions.

Portable, and ultrasensitive HR-HPV tests based on nucleic acid biosensors.

Cervical cancer is the third most common cancer threatening women's health globally, and high-risk human papillomavirus (HR-HPV) infection is the main cause of cervical cancer worldwide. Given the recurrent nature of HR-HPV infection, accurate screening is essential for its control. Since the commonly used polymerase chain reaction (PCR) technique is limited by professional equipment and personnel, convenient and ultrasensitive detection methods for HR-HPV are still highly needed. As new molecular detection methods, nucleic acid amplification-based biosensors have the advantages of high sensitivity, rapid operation, and portability, which are helpful for point-of-care testing in rural and remote areas. This review summarized nucleic acid biosensors for HR-HPV screening based on a variety of nucleic acid amplification strategies involved in improved PCR, loop-mediated isothermal amplification, recombinase polymerase amplification, hybridization chain reaction, catalyzed hairpin assembly, and CRISPR/Cas systems. In combination with microfluidic technology, lateral flow assays, electrochemical analysis and other sensing technologies, HR-HPV nucleic acid biosensors have the advantages of high throughput, short response time, high sensitivity and easy operation in the field. Although there are still shortcomings, such as high cost and poor reproducibility, this approach will be suitable for on-site screening of HR-HPV infection or cervical cancer and for auxiliary clinical diagnosis in complex environments and poor areas in the future.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Prevalence of genital high-risk human papillomavirus infections and associated factors among women living with human immunodeficiency virus in Uganda

BackgroundWomen living with HIV are at risk for cervical dysplasia and cancer worldwide. In 2015, the World Health Organization (WHO) recommended that testing for high-risk HPV (hrHPV) infection be incorporated into cervical cancer screening programs using molecular nucleic acid tests (NATs) but this has not previously been done in Uganda. The country’s coverage for Human Papilloma Virus (HPV) screening remains low at less than 10% for women aged 25–49 years. This study determined the genital prevalence of hrHPV infection and the associated factors among women living with HIV in Uganda.MethodsA descriptive cross-sectional study was conducted in 15 selected health facilities among participants who were on Antiretroviral therapy (ART). Participants who consented to participate were instructed on how to collect their own high vaginal swabs using a cervical brush for HPV molecular testing (HPV DNA or HPV RNA) and their demographics data was collected using a standard questionnaire. Laboratory diagnosis for HPV molecular testing was done using Gene xpert machines and Hologic Aptima Machine. Modified Poisson regression analysis was conducted to determine the associated factors.ResultsThis study involved 5856 HIV positive participants on ART. A total of 2006 out of 5856 (34.3%) participants had high risk HPV infections. HPV infections by genotypes were: HPV16 317(15.8%), HPV 18/45 308 (15.4%) and other high-risk HPV 1381 (68.8%). The independent factors associated with all hrHPV were parity, education level, having more than one partner, and engaging in early sex. Smoking was associated with HPV 16, HPV 18/45 and other hrHPV. Age was associated with all hrHPV, marital status with HPV 16, and occupation with HPV 16.ConclusionsThe prevalence of genital high-risk HPV infections among HIV positive women attending ART clinics in public facilities in Uganda was high. Other hrHPV genotype was the commonest compared to 18/45 and HPV 16. The integration of cervical cancer screening in ART programmes remains paramount to support the early detection of cervical cancer and Non-invasive self-collected urine and vaginal sampling for cervical cancer screening present an opportunity.

Retrospective analysis of cytology and high-risk HPV testing in 1067 endocervical adenocarcinomas and precursor lesions.

Cytology and high-risk human papilloma virus (hrHPV) cotesting is the mainstay in the detection of cervical carcinoma. Endocervical adenocarcinoma (EAC) is divided into HPV-associated adenocarcinoma (HPVA) and HPV-independent adenocarcinoma (HPVI) by the World Health Organization classification (2020). The detection effect of cotesting is suggested to be different among EAC subtypes and precursors, but has not well-documented yet. In this study, the authors retrospectively analyzed cotesting among adenocarcinoma in situ (AIS), HPVA, and HPVI. The cohort included 569 AIS and 498 EAC consisting of 371 (74.5%) HPVA, 111 (22.3%) HPVI, and 16 (3.2%) adenocarcinoma, not otherwise specified. The authors found that AIS patients were significantly younger than HPVA and HPVI (mean±SD, years: 40.7±8.6; HPVA, 44.8±9.3; HPVI, 50.0±11.3; p<.001) and had a higher prevalence of concurrent squamous intraepithelial lesions (75.5%, HPVA, 37.2%; HPVI, 12.6%; p<.001). The detection rate of hrHPV test or cytology was substantially higher in AIS and HPVA than in HPVI (97.7% and 90.2% vs. 16.5%, p<.001, or 71.1% and 71.9% vs. 60.7%, p=.042, respectively). Cytology and hrHPV cotesting was superior to a single test in the detection of EAC and AIS. The detection rate of cotesting amounted to 100% in AIS and 94.3% in HPVA but was substantially lower in HPVI (72.2%) (p<.001). The authors conclude that cytology and hrHPV cotesting can maximize the detection effect for HPVA and AIS but is not optimal for HPVI.

Vaginal pH value can affect the susceptibility to human papillomavirus infection

BackgroundCervical cancer is the fourth most common cancer among women, with persistent high-risk human papillomavirus (HPV) infection being responsible for its progression. In healthy, pre-menopausal women, the vaginal pH value is maintained at 3.8–4.5, but various factors can affect it. Previous studies have suggested the relationship between vaginal pH value and HPV infection. In this study, we aimed to explore the relationship between vaginal pH and susceptibility of HPV infection.MethodsIn our study, we retrospectively collected medical information from women who underwent leukorrhea examination at our hospital. We excluded women with infectious diseases or cancer, those who were pregnant or within 6 months post-delivery, and those without HPV test results within 6 months. The association between percentage of HPV infection and vaginal pH value was analyzed. Furthermore, we prepared HPV pseudovirus (PsVs) by co-transfecting structure plasmids and report plasmids in 293FT cells. In vitro, we changed the pH value of cell culture medium to investigate its influence on HPV PsVs infection. In vivo, we changed mouse’s vaginal pH value to investigate its influence on HPV PsVs infection.ResultsOur retrospective study included 3115 women aged 20–78, including 2531 women with HPV negative and 584 women with HPV positive. The percentages of both HPV infection and high-risk HPV infection were higher in women with a vaginal pH value ≥5.0 compared to those with a pH value < 5.0. In vitro, HPV PsVs infection rate was higher in cell culture medium of higher pH value, dominantly due to the influence of pH value on the stage of HPV PsVs adhering to cell surface. Neither of the cell surface HPV receptors Syndecan-1 nor integrin α6 was found to be changed obviously in different pH values. In vivo, more HPV PsVs were adhered to the mouse’s vaginal epithelial cells with the increase of the vaginal pH value.ConclusionsOur study suggests a possible association between vaginal pH value and HPV infection. The pH value can influence the susceptibility of HPV PsVs infection by affecting the adhering of HPV PsVs to cells in vivo and in vitro. Additionally, the cell surface HPV receptors Syndecan-1 and Integrin α6 do not seem to be affected by pH value, and the specific mechanism needs to be further explored.

Performance of BD Onclarity HPV assay on FLOQSwabs vaginal self-samples.

Human papillomavirus (HPV) testing on self-collected vaginal samples has been shown to improve women's participation to cervical cancer screening programs, particularly in regions with limited access to health care. Nevertheless, the introduction of self-sampling in cervical cancer screening programs requires prior clinical validation of the HPV assay in combination with a self-sample collection device, including also the laboratory workflow and automation required for high-throughput testing in screening. In this study, the performance of BD Onclarity HPV on FLOQSwab-collected vaginal self-samples has been compared to clinician-taken liquid-based cytology samples, to detect high-grade cervical intraepithelial neoplasia using two high-throughput platforms, BD Viper LT and BD COR. The study findings have shown a similar performance of BD Onclarity on testing self-collected samples, confirming the validation of the proposed pre-analytical and analytical protocols for their use in cervical cancer screening programs based on self-collected vaginal samples.

Community Screening for High-Risk Human Papilloma Virus Infection using Self-Sampling and 'Point-Of-Care' Test.

HR-HPV types 16 and 18 are responsible for pre-invasive and invasive lesions of the cervix, accounting for 70-80% of the total subtypes. The aim of this study was to investigate the prevalence of high-risk HPV subtypes 16 and 18 in self-collected vaginal samples using real-time micro-PCR and to study the acceptability of self-sampling. Eligible women (30-65 years) were screened from a semi-urban area of Uttarakhand (India) using self-sampling. High-risk HPV genotypes (16/31 and 18/45) were tested using real-time micro-PCR technique with results available in one hour. The positive results were validated by standard RT-PCR for high-risk HPV 16, 18, separately and for 12 other high-risk genotypes, combined. Ease of the procedure, level of comfort, and recommendation to other women were studied and the acceptability of self-sampling was analyzed using the Likert scale. Of 975 eligible women screened, 45 participants tested positive for HR-HPV (16/31,18/45) using real-time micro-PCR with a prevalence of 4.6%. Positive samples were further tested through routine RT-PCR and 60% were found to be HR-HPV 16 and 18 positive. For self-sampling, 96.72% (n=943) participants were 'very satisfied' and 94.15% (n=918) found self-sampling to be 'very comfortable' and 88.51% (n=863) stated that they will strongly recommend this test to other eligible women in the community. We conclude that HR-HPV testing with limited genotyping showed a prevalence of 4.6%, 60% of these were HPV 16/18 positive. Point of care testing was feasible in the community and self-sampling was acceptable.

International Anal Neoplasia Society's consensus guidelines for anal cancer screening.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing

Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

Feasibility and acceptability of an HPV self-testing strategy: lessons from a research context to assess for ability to implement into primary care at a national level in Botswana.

The WHO strategy for cervical cancer elimination strives to achieve 70% coverage with high-performance cervical screening. While few low- and middle-income countries have achieved this, high-risk human papillomavirus (hrHPV) self-testing creates the possibility to rapidly upscale access to high-performance cervical screening across resource settings. However, effective hrHPV screening requires linkage to follow-up, which has been variable in prior studies. This study developed and tested an implementation strategy aimed at improving screening and linkage to follow-up care in South East District in Botswana. This study performed primary hrHPV self-testing; those with positive results were referred for a triage visit. Withdrawals for any reason, loss-to follow-up between hrHPV test and triage visit, and number of call attempts to give hrHPV results were also documented. Acceptability of the program to patients was measured as the proportion of patients who completed a triage visit when indicated, meeting the a priori threshold of 80%. Feasibility was defined as the proportion of participants receiving the results and attending follow-up. To assess the associations between participant characteristics and loss-to-follow-up we used log-binomial regressions to estimate risk ratios and 95% confidence intervals (CI). Enrollment of 3,000 women occurred from February 2021 to August 2022. In total, 10 participants withdrew and an additional 33 were determined ineligible after consent, leaving a final cohort of 2,957 participants who underwent self-swab hrHPV testing. Half (50%) of participants tested positive for hrHPV and nearly all (98%) of participants received their hrHPV results, primarily via telephone. Few calls to participants were required to communicate results: 2,397 (82%) required one call, 386 (13%) required 2 calls, and only 151 (5%) required 3-5 calls. The median time from specimen collection to participant receiving results was 44 days (IQR, 27-65). Of all hrHPV positive participants, 1,328 (90%) attended a triage visit. In a large cohort we had low loss-to-follow-up of 10%, indicating that the strategy is acceptable. Telephonic results reporting was associated with high screening completion, required few calls to participants, and supports the feasibility of hrHPV self-testing in primary care followed by interval triage.

Human Papillomavirus Types and Cervical Cancer Screening among Female Sex Workers in Cameroon.

Female sex workers (FSWs) are at high risk for sexually transmitted infections (STIs), including infection with human papillomavirus (HPV) and cervical cancer due to occupational exposure. The objective of this study was to estimate the prevalence of HPV, HPV types, and precancerous lesions of the cervix among FSWs in Cameroon. In this cross-sectional study, FSWs in Cameroon aged 30 years and above were screened for cervical cancer using high-risk HPV testing and genotyping and visual inspection with acetic acid and Lugol's iodine (VIA/VILI) enhanced using digital cervicography (DC) simultaneously. Those who were positive for VIA/VILI-DC were provided treatment with thermal ablation (TA) immediately for cryotherapy/TA-eligible lesions while lesions meeting the criteria for large loop excision of the transformation zone (LLETZ) were scheduled at an appropriate facility for the LLETZ procedure. HPV-positive FSWs without any visible lesion on VIA/VILI-DC were administered TA. Bivariate analyses were conducted to compare demographic and clinical characteristics. Crude and adjusted logistic regression models were computed for HPV infection status and treatment uptake as outcomes in separate models and their ORs and 95% confidence intervals (95% CI) were reported. Among the 599 FSWs aged 30 years and older that were screened for HPV and VIA/VILI-DC, 62.1% (95% CI: (0.58-0.66)) were positive for one or more HPV types. HPV type 51 had the highest prevalence (14%), followed by types 53 (12.4%) and 52 (12.2%). Type 18 had the lowest prevalence of 2.8% followed by type 16 with 5.2%. In the multivariable model, HIV-positive FSWs were 1.65 times more likely to be infected with HPV compared to their HIV-negative counterparts (AOR: 1.65, CI: 1.11-2.45). A total of 9.9% of the 599 FSWs were positive for VIA/VILI-DC. The prevalence of HPV infection among FSWs in Cameroon is higher than the worldwide pooled FSW prevalence. HPV types 51 and 53 were the most prevalent, while types 18 and 16 were the least prevalent. HIV status was the only variable that was significantly associated with infection with HPV.

Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy.

The aim of this study was to investigate the significance of colposcopy in diagnosing cervical lesions when negative cervical cytology is combined with positive human papillomavirus (HPV). Overall, 370 patients with cervical epithelial lesions who had negative cervical fluid-based cytology combined with positive HPV results were selected and analysed for severity of cervical lesions and HPV distribution. Among the patients with cervical lesions, 242 had a single HPV infection, and 128 cases had multiple infections. No significant difference was found between HPV single infection and multiple infections in both groups of patients with cervical lesions (P > 0.05). Furthermore, 137 had non-HPV 16 and 18, accounting for 37.30% of all the patients with cervical lesions. Among them, HPV 52, 58, and 33 infections were the most common at 38.69, 30.66 and 29.20%, respectively - significantly higher than other high-risk HPV types (P < 0.05). High-risk HPV testing is crucial in patients with negative cervical fluid-based cytology combined with positive HPV results. Patients with HPV 16 and 18 and those with simple HPV 52, 58, and 33 infections should undergo timely colposcopy.