HPV-based Screening Research Articles

Are Canadian Women Prepared for the Transition to Primary HPV Testing in Cervical Screening? A National Survey of Knowledge, Attitudes, and Beliefs.

As Canadian provinces and territories prepare to transition to HPV-based primary screening for cervical cancer, failure to identify and address potential barriers to screening could hinder program implementation. We examined screening-eligible Canadians' attitudes towards and knowledge of cervical screening. A nationally representative sample of screening-eligible Canadians (N = 3724) completed a web-based survey in the summer of 2022. Oversampling ensured that half of the sample were underscreened for cervical cancer (>3 years since previous screening or never screened). The participants completed validated scales of cervical cancer, HPV, and HPV test knowledge and HPV test and self-sampling attitudes and beliefs. Between-group differences (underscreened vs. adequately screened) were calculated for scales and items using independent sample t-tests or chi-square tests. The underscreened participants (n = 1871) demonstrated significantly lower knowledge of cervical cancer, HPV, and the HPV test. The adequately screened participants (n = 1853) scored higher on the Confidence and Worries subscales of the HPV Test Attitudes and Beliefs Scale. The underscreened participants scored higher on the Personal Barriers and Social Norms subscales. The underscreened participants also endorsed greater Autonomy conferred by self-sampling. Our findings suggest important differential patterns of knowledge, attitudes, and beliefs between the underscreened and adequately screened Canadians. These findings highlight the need to develop targeted communication strategies and promote patient-centered, tailored approaches in cervical screening programs.

Testing for Human Papillomaviruses in Urine, Blood, and Oral Specimens: an Update for the Laboratory.

Twelve high-risk alpha human papillomavirus (HPV) genotypes cause approximately 690,000 cancer cases annually, with cervical and oropharyngeal cancer being the two most prominent types. HPV testing is performed in laboratory settings for various applications of a clinical, epidemiological, and research nature using a range of clinical specimens collected by clinicians or by individuals (self-collected specimens). Here, we reflect on the importance and justification of using the right test for the right application and provide practical updates for laboratories either participating in or anticipating involvement in HPV testing in three specimen types, namely, urine, blood, and oral specimens, which are considered "alternative" specimens by many. In addition to clinician-collected cervical samples and self-collected cervicovaginal samples, first-void urine is emerging as a credible specimen for HPV-based cervical cancer screening, triage of HPV screen-positive women, monitoring HPV vaccine impact, and HPV testing in groups for which a less invasive sample is preferred. Detection of cell-free DNA (including HPV DNA) in blood has great promise for the early detection of HPV-attributable oropharyngeal cancer (HPV-AOC) and potentially other HPV-driven cancers and as an adjunct prognostic marker in long-term tumor surveillance, including treatment response. The moderate sensitivity of HPV testing in oral rinses or swabs at HPV-AOC diagnosis prevents its use in HPV-AOC secondary prevention but represents a promising prognostic tool in HPV-AOC tertiary prevention, where the HPV persistence in oral rinses throughout treatment may predict early HPV-AOC recurrences and/or the development of secondary HPV-AOC. The increasing sophistication of specific collection devices designed for alternative samples and the enhanced precision of novel molecular technologies are likely to support the evolution of this field and catalyze potential translation into routine practice.

Protocol for the formative phase of a trial (SHE-CAN) to test co-designed implementation strategies for HPV-based cervical screening among vulnerable women in two diverse settings in India

BackgroundIn view of the WHO’s call for the elimination of cervical cancer as a public health problem, and current low screening coverage, Indian policy makers need evidence on how to effectively implement cervical screening programmes, ensuring equity in access.Our study will follow the INSPIRE implementation framework to co-design and test HPV-based screening approaches in two states of India with different health system organisation, based on understanding the status of screening as currently implemented, readiness and challenges to transition to HPV-based screening, and preferences of key stakeholders. Here, we describe our protocol for the formative phase of the study (SHE-CAN).MethodsThe study population includes women from vulnerable populations, defined as residents of tribal areas, rural villages, and urban slums, in the states of Mizoram and Tamil Nadu. The baseline assessment will use mixed methods research, with desktop reviews, qualitative studies, and surveys. A capacity assessment survey of screening and treatment facilities will be done, followed by interviews with healthcare providers, programme managers, and community health workers. Interviews will be conducted with previously screened women and focus group discussions with under and never-screened women and community members. Stakeholder workshops will be held in each state to co-design the approaches to delivering HPV-based screening among 30–49-year-old women.DiscussionThe quality and outcomes of existing screening services, readiness to transition to HPV-based screening, challenges in providing and participating in the cervical cancer care continuum, and acceptability of screening and treatment approaches will be examined. The knowledge gained about the current system, as well as recognition of actions to be taken, will inform a stakeholder workshop to co-design and evaluate implementation approaches for HPV-based screening through a cluster randomised implementation trial.

The features of high-risk human papillomavirus infection in different female genital sites and impacts on HPV-based cervical cancer screening

BackgroundThe causal role of high-risk Human papillomavirus (HR-HPV) in the pathogenesis of anogenital cancers is well established. In contrast, information on HR-HPV distribution of continuous anatomic sites within the female genital tract is limited, and the impact of sample type on the clinical performance in HPV-based cervical cancer screening warrants investigation.MethodsA total of 2,646 Chinese women were enrolled in the study from May 2006 to April 2007. We analyzed the infection features by infection status and pathological diagnoses of 489 women with complete HR-HPV type and viral load data on the cervix, upper vagina, lower vagina, and perineum samples. Additionally, we assessed the clinical performance for detecting high-grade cervical intraepithelial neoplasia of grade two or worse (≥ CIN2) among these four types of samples.ResultsHR-HPV positivity rate was lower in the cervix (51.53%) and perineum (55.83%), higher in the upper (65.64%) and lower vagina (64.42%), and increased with the severity of cervical histological lesions (all P<0.001). Single infection was more dominant than multiple infections at each anatomic site of the female genital tract. The proportion of single HR-HPV infection decreased successively from the cervix (67.05%) to the perineum (50.00%) (Ptrend=0.019) in cervical intraepithelial neoplasia grade 1 (CIN1) and was higher in samples of the cervix (85.11%) and perineum (72.34%) in ≥ CIN2. In addition, the highest viral load was observed in the cervix compared to the other three sites. The overall agreement of the cervical and perineum samples was 79.35% and increased continuously from normal (76.55%) to ≥ CIN2 (91.49%). As for the detection of ≥ CIN2, the sensitivity was 100.00%, 97.87%, 95.74%, and 91.49% for the cervix, upper vagina, lower vagina, and perineum samples, respectively.ConclusionsSingle HR-HPV infection predominated throughout the female genital tract, but the viral load was lower compared to multiple HR-HPV infections. Despite the decreasing viral load from cervix to perineum, the clinical performance for detecting ≥ CIN2 of the perineum sample was comparable to that of the cervix.

A retrospective analysis of human papillomavirus (HPV) prevalence and genotype distribution among 25,238 women in Shanghai, China revealed the limitations of current HPV-based screening and HPV vaccine

BackgroundTo determine the human papillomavirus (HPV) type-specific prevalence and distribution among women with various age and cervical lesions in Shanghai, China. And to evaluate the carcinogenicity of different high-risk HPV (HR-HPV) and the efficacy of HR-HPV testing and HPV vaccine. MethodsThe clinical data from 25,238 participants who received HR-HPV testing (HPV GenoArray test kit, HybriBio Ltd) at the Affiliated Hospital of Tongji University from 2016 to 2019 were reviewed and analyzed using SPSS (version 20.0, Tongji University, China). ResultsThe overall prevalence of HPV was 45.57% in the study population, of which 93.51% were found HR-HPV infection. The three most prevalent HR-HPV genotypes were HPV 52 (22.47%), 16 (16.4%) and 58 (15.93%) among HPV-positive women, and HPV 16 (43.30%), 18 (9.28%) and 58 (7.22%) in women with histologically confirmed cervical cancer (CC). 8.25% of CC were found to be HPV negative. Only 83.51% of CC cases were related to the HPV genotypes covered by nine-valent HPV vaccine. HPV prevalence and genotype distribution varied with age and cervical histology. The odds ratios (OR) of HR-HPV for CC were also different, among which the top three types were HPV 45 [OR= 40.13, 95% confidence intervals (CI) 10.37–155.38], 16 (OR=33.98, 95%CI 15.90–72.60) and 18 (OR=21.11, 95%CI 8.09–55.09). The increase in the types of HPV infection did not increase the risk of CC correspondingly. As the primary cervical screening method, HR-HPV testing showed the high sensitivity (93.97%, 95%CI 92.00–95.49) but low specificity (42.82%, 95%CI 41.81–43.84). ConclusionsOur study provide the comprehensive epidemiological data on HPV prevalence and genotype distribution among Shanghai women with various cervical histology, which can not only serve as a significant reference for clinical practice, but also implicated the need of more effective CC screening methods and HPV vaccine covering more subtypes.

Evaluation of DNA methylation biomarkers ASCL1 and LHX8 on HPV-positive self-collected samples from primary HPV-based screening

BackgroundHost-cell DNA methylation analysis can be used to triage women with high-risk human papillomavirus (HPV)-positive self-collected cervicovaginal samples, but current data are restricted to under-/never-screened women and referral populations. This study evaluated triage performance in women who were offered primary HPV self-sampling for cervical cancer screening.MethodsSelf-collected samples from 593 HPV-positive women who participated in a primary HPV self-sampling trial (IMPROVE study; NTR5078), were tested for the DNA methylation markers ASCL1 and LHX8 using quantitative multiplex methylation-specific PCR (qMSP). The diagnostic performance for CIN3 and cervical cancer (CIN3 + ) was evaluated and compared with that of paired HPV-positive clinician-collected cervical samples.ResultsSignificantly higher methylation levels were found in HPV-positive self-collected samples of women with CIN3 + than control women with no evidence of disease (P values <0.0001). The marker panel ASCL1/LHX8 yielded a sensitivity for CIN3 + detection of 73.3% (63/86; 95% CI 63.9–82.6%), with a corresponding specificity of 61.1% (310/507; 95% CI 56.9–65.4%). The relative sensitivity for detecting CIN3+ was 0.95 (95% CI 0.82–1.10) for self-collection versus clinician-collection, and the relative specificity was 0.82 (95% CI 0.75–0.90).ConclusionsThe ASCL1/LHX8 methylation marker panel constitutes a feasible direct triage method for the detection of CIN3 + in HPV-positive women participating in routine screening by self-sampling.

Health and economic impact of delaying large-scale HPV vaccination and screening implementation on cervical cancer in China: a modelling study

Current uptake of HPV vaccination and screening in China is far below World Health Organization 2030 targets for cervical cancer elimination. We quantified health and economic losses of delaying large-scale HPV vaccination and screening implementation in China. We used a previously validated transmission model to project lifetime health benefits, costs, effectiveness, and timeline for cervical cancer elimination of alternative scenarios, including combining HPV vaccination initiated from 2022 to 2030 with screening in different modalities and coverage increase rates, as well as screening alone. All women living or projected to be born in China during 2022-2100 were considered. We employed a societal perspective. Regardless of vaccine type, immediate large-scale vaccination initiated in 2022 and achieving 70% coverage of HPV-based screening in 2030 (no-delay scenario) would be the least costly and most effective. Compared with the no-delay scenario, delaying vaccination by eight years would result in 434,000-543,000 additional cervical cancer cases, 138,000-178,000 deaths, and $2863-4437 million costs, and delay elimination by 9-10 years. Even with immediate vaccination, the gradual scale-up of LBC-based screening to 70% coverage in 2070 would result in 2,530,000-3,060,000 additional cases, 909,000-1,040,000 deaths, and $5098-5714 million costs compared with no-delay scenario, and could not achieve elimination if domestic 2vHPV or 4vHPV vaccines are used (4.09-4.21 cases per 100,000 woman in 2100). Delaying large-scale HPV vaccination and/or high-performance screening implementation has detrimental consequences for cervical cancer morbidity, mortality, and expenditure. These findings should spur health authorities to expedite large-scale vaccine rollout and improve screening. Bill & Melinda Gates Foundation (INV-031449 and INV-003174) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-004).

Abstract NG13: Feasibility of topical self-administered therapies to improve cervical precancer treatment outcomes among women living with HIV in low-and middle-income countries

Abstract Global trends of invasive cervical cancer (ICC) represent a dire global health inequity, with 85 percent of incident cases and 90 percent of deaths occurring in low- and middle-income countries (LMICs).1 ICC is the leading cause of cancer death among women living with HIV (WLWH) in sub-Saharan Africa, which accounts for 71% of the global burden of HIV infection, despite being home to only 12% of the global population.2 Compared to HIV-negative women, WLWH have increased incidence and persistence of human papillomavirus (HPV),3 have a shorter time from HPV infection to development of precancerous lesions,4 and have a six to eightfold increased risk of developing invasive cancer.5 In 2020, the World Health Organization (WHO) launched the 90/70/90 global strategy for cervical cancer elimination, which aims for 90% human papillomavirus (HPV) vaccination rate, 70% screening coverage, and 90% of precancerous lesions adequately treated by 2030. Current efforts towards this elimination agenda include scaling up HPV-based screening programs as well as improving access to precancer treatment using portable ablation and excisional devices in LMICs. However, among WLWH, current precancer treatment methods are limited by high rates of treatment failure. In a randomized trial of WLWH with cervical intraepithelial neoplasia grade 2/3 (CIN2/3), recurrence at 24 months was 30% in the ablation arm and 19% in the excision arm.6 These high rates of treatment failure, demonstrated in multiple studies, are driven by persistent HPV infection following treatment,7 and are highly consequential in LMICs settings follow-up mechanisms are weak. This highlights an urgent need for studies on feasible, innovative, yet accessible strategies to improve HPV clearance following precancer treatment for WLWH in LMICs. Use of self-administered topical therapies with anti-viral properties as adjunct treatment could be a feasible and highly scalable strategy to address this limitation. Several studies, have demonstrated the safety, and efficacy of 5-Flourouracil (5FU), a readily available topical drug as primary or adjuvant therapy for CIN2/3 among both HIV-positive and HIV-negative women in the U.S. In a Phase III multicenter trial of U.S WLWH with CIN2/3 randomized to self-administered intravaginal 5-Flourouracil (5FU) versus observation following standard treatment, participants in the 5FU arm had an 8% CIN2/3 recurrence rate at 18 month follow-up, compared to 31% in the observation arm (p=0.04).8 In another randomized trial of self-administered 5FU as primary treatment versus 6-month observation for CIN grade 2 (CIN2) among U.S women without HIV infection, 93% in the 5FU arm had disease regression, compared to 56% in the observation arm (p=0.01).9 In this study, 50% of participants in the 5FU arm cleared HPV at follow-up, compared to 22% in the observation arm (p&amp;lt;0.05). In both studies, 5-FU, used once every other week for 8 applications, was safe, with no grade 3 or 4 adverse events, and compliance and adherence to treatment was high. However, there are no studies evaluating whether self-administered therapies would be culturally acceptable to WLWH and their male partners in LMICs, or whether topical 5FU may be in this population. To fill this gap, with the support of the 2022 Victoria’s Secret Global Fund for Women’s Cancers Career Development award, in partnership with Pelotonia &amp; the American Association for Cancer Research, using in-depth-interviews and focus group discussions, I am carrying out a mixed-methods qualitative study among WLWH with HPV and their male partners in Kenya and Malawi to investigate their perceptions towards using self-administered therapies for HPV and cervical precancer treatment, as well as perceived barriers and facilitators to uptake. Additionally, I will conduct a Phase I trial to evaluate the safety and adherence of self-administered intravaginal 5-FU following primary treatment among WLWH with CIN2/3 in Kenya. These studies will generate key preliminary data to support future randomized trials to investigate the efficacy of 5FU as adjuvant therapy to improve current precancer treatment strategies for WLWH in LMICs.

Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology

Background: A plethora of data supports HPV-based screening to be the preferred strategy for cervical cancer prevention. The shift to a more sensitive first-line test brings the need of effective triage up for discussion. Currently, most algorithms apply cytology as a triage of HPV-DNA positive women. This study compared the performance of a 7-type HPV-mRNA test to cytology. Methods: From 1 January 2019 until 31 December 2021, cervical samples from 58,029 women were examined at the University Hospital of North Norway. A total of 30.5% (17,684/58,029) fulfilled the criteria for HPV-DNA primary screening. All positive samples were triaged by cytology and followed-up according to national guidelines through 2022. Additionally, a 7-type HPV-mRNA test was applied. The study endpoint was a histologically confirmed high-grade lesion (CIN2+). Results: A total of 5.6% (990/17,684) had positive HPV-DNA test, 97.2% (962/990) with valid HPV-mRNA results. A total of 55.5% (534/962) had abnormal cytology (ASC-US+), and 35.1% (338/962) had a positive HPV-mRNA test. A total of 13.9% (134/962) had CIN2+. The sensitivity (CIN2+) of cytology versus the HPV-mRNA test was 76.1% (102/134) versus 73.1% (98/134), p = 0.67. The specificity was 47.8% (396/828) versus 71.0% (588/624), p &lt; 0.001. PPV was 19.1% (102/534) and 29.0% (98/338), p &lt; 0.001, respectively. The number of colposcopies per CIN2+ detected by cytology and HPV-mRNA test was 5.2 and 3.1. Conclusion: The 7-type HPV mRNA test was significantly more specific than cervical cytology in a triage of HPV-DNA positive women. Using this biomarker as the threshold for colposcopy may better balance the benefits and harms of screening.

High-risk human papillomavirus genotype distribution among women with gynecology complaints in northwest Ethiopia

BackgroundHuman papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities.MethodsA health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar–Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany.ResultsWe included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8–58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer.ConclusionsHR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia.

Understanding the Challenges of HPV-Based Cervical Screening: Development and Validation of HPV Testing and Self-Sampling Attitudes and Beliefs Scales.

The disrupted introduction of the HPV-based cervical screening program in several jurisdictions has demonstrated that the attitudes and beliefs of screening-eligible persons are critically implicated in the success of program implementation (including the use of self-sampling). As no up-to-date and validated measures exist measuring attitudes and beliefs towards HPV testing and self-sampling, this study aimed to develop and validate two scales measuring these factors. In October-November 2021, cervical screening-eligible Canadians participated in a web-based survey. In total, 44 items related to HPV testing and 13 items related to HPV self-sampling attitudes and beliefs were included in the survey. For both scales, the optimal number of factors was identified using Exploratory Factor Analysis (EFA) and parallel analysis. Item Response Theory (IRT) was applied within each factor to select items. Confirmatory Factor Analysis (CFA) was used to assess model fit. After data cleaning, 1027 responses were analyzed. The HPV Testing Attitudes and Beliefs Scale (HTABS) had four factors, and twenty-two items were retained after item reduction. The HPV Self-sampling Attitudes and Beliefs Scale (HSABS) had two factors and seven items were retained. CFA showed a good model fit for both final scales. The developed scales will be a valuable resource to examine attitudes and beliefs in anticipation of, and to evaluate, HPV test-based cervical screening.

HPV prevalence and genotype distribution among women in eastern China during the Covid-19 pandemic

ABSTRACT Since March 2020, the pandemic caused by SARS-CoV-2 has affected nearly all aspects of daily life. In this study, we investigated the age-stratified prevalence and genotype distribution of human papillomavirus (HPV) among females in Shandong province (eastern China) and aimed to provide guidance on HPV-based cervical cancer screening and vaccination. The distribution of HPV genotypes was analyzed using PCR-Reverse Dot Hybridization. The overall infection rate of HPV was 16.4%, which was dominated by high-risk genotypes. The most prevalent genotype was HPV16 (2.9%), followed by HPV52 (2.3%), HPV53 (1.8%), HPV58 (1.5%), and HPV51 (1.3%). Among the positive cases with HPV infection, single-genotype infection was significantly higher than that of multi-genotype infection. In subgroup analyses by age (≤25, 26–35, 36–45, 46–55, >55), HPV16, 52, and 53 were consistently the three most common hrHPV genotypes in all age groups. The infection rate of multi-genotypes in the ≤25 and >55 age groups was significantly higher than that in other age groups. A bimodal distribution of HPV infection rate was observed in different age groups. Among lrHPV genotypes, HPV6, HPV11, and HPV81 were the three most common types in the ≤25 age group, while in other age groups, HPV81, HPV42, and HPV43 are the three most common lrHPV genotypes. This study provides basic information on the distribution and genotypes of HPV in the female population in eastern China, which could improve the application of HPV diagnostic probes and vaccines.

HPV typing as the method of choice in the prevention and early detection of cervical cancer

Background: Human papillomavirus (HPV) is recognized as the primary cause of cervical cancer (CC), and significant coexisting factors have also been identified. CC is considered a curable disease because it has a long preinvasive period. It is possible to organize effective screening, and the treatment of preinvasive lesions is successful. Aim: To show the importance of HPV typing in the early detection of premalignant cervical disease. Method: Literature review, synthesis, and extraction of key professional and contemporary literature. Results: Depending on the methods used in identification, the presence of different types of HPV was identified in about 90% of intraepithelial neoplasia and CC samples. HPV genotyping plays an important role in the detection of dysplasia and helps to reduce the number of false-positive Pap test results. Randomized controlled trials have shown that CC screening with HPV testing offers greater protection against cervical precancer and cancer compared with cytology-based screening. To date, it has been proven that HPV 16 and 18 genotypes have the highest oncogenic potential. These two genotypes are responsible for about 70% of all squamous cell carcinomas, 30-40% of vulvar cancers, and about 85% of cervical adenocarcinomas. According to a recent report, 48 (35%) of 139 countries recommended HPV-based cervical screening, with most currently switching from cytology to HPV testing. Conclusion: HPV typing can be of great benefit in the early detection of malignant transformation of infected cells and the prevention of CC.

Older women testing positive for HPV16/18 on cervical screening and risk of high-grade cervical abnormality.

In Australia's HPV-based cervical screening program, we previously showed that risk of histological high-grade abnormality at 1year post screening decreased with age in women with oncogenic HPV. In this study, we followed 878 HPV16/18 positive women aged 55 years and over for up to 3 years post screening test, to determine the proportion with histological high-grade abnormality (HGA, incorporating high-grade squamous intraepithelial abnormality (HSIL), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma) and to correlate risk of HGA with liquid-based cytology result and with prior screening history. HGA was detected in 7.8% at 1year and 10.0% at 3 years, with no significant difference (P=.136), despite the number of women with follow-up information significantly increasing from 82.9% to 91.0% (P < .0001). The proportion of HPV16/18 positive women with HGA at 3 years was highest in those with an HSIL cytology result (79.0%) and lowest in those with negative cytology (6.2%). Women with an adequate screening history had fewer HGA than such women with inadequate prior screening (6.6% vs 16.0%, P=.001) or with a history of an abnormality (6.6% vs 14.4%, P=.001). HPV16/18 infection in women over 55 years may have a different natural history from that in younger women, in whom HGA are more common after HPV16/18 detection. In HPV-based cervical screening programs, management algorithms for screen-detected abnormalities based on risk stratification should include factors such as age, screening history and index cytology result, so that women receive appropriate investigation and follow-up.

Incorporating HPV 33 and cytology into HPV 16/18 screening may be feasible. A cross-sectional study.

The distribution of human papillomavirus (HPV) varies geographically, and each country is making its screening and vaccination program. This study questioned the need for colposcopy for HPV types other than HPV 16 and 18, and the need for cytology incorporated into HPV testing. 1043 consecutive patients referred for colposcopy are included in this retrospective study. Logistic regression analysis, ANOVA, and Pearson's correlation were used for statistical analysis. The value of p < 0.05 was considered statistically significant. HPV 16 was the most common HPV type referred, followed by HPV 18, 52, 51, and 31, respectively. HPV 16 tends to be positive in younger patients than other HPV types (p < 0.05). Only HPV 16 (OR: 1.41, 1.06-1.88 95% CI) and HPV 33 (OR: 2.23; 1.06-4.64 95% CI) (p < 0.05) had significant prediction for CIN 2 + lesions. In patients with only a cytological abnormality, cytological abnormality with single other high-risk (hr) HPV (without HPV 16 or 18) or double other hrHPV positivity but without HPV 16 and 18 infections, we detected 159 (19%) CIN 2 + lesions. HPV 33 may be implemented in hrHPV screening protocols for direct colposcopy referral as well as HPV 16 and HPV 18 in specific regions. If we had opted for HPV-based screening only for HPV 16 and 18 without cytology, 19% of all CIN 2 + lesions would have been missed. HPV-based screening only with HPV 16 and 18 may not be feasible. Nonavalent vaccines should be considered for the vaccination of specific populations.

Implementing HPV testing in 9 Latin American countries: The laboratory perspective as observed in the ESTAMPA study.

Replacement of cytology screening with HPV testing is recommended and essential for cervical cancer elimination. HPV testing for primary screening was implemented in 12 laboratories within 9 Latin American countries, as part of the ESTAMPA cervical cancer screening study. Our observations provide information on critical operational aspects for HPV testing implementation in diverse resource settings. We describe the implementation process of HPV testing in ESTAMPA, focusing on laboratory aspects. We assess the readiness of 12 laboratories to start HPV testing and their continuity capacity to maintain good quality HPV testing until end of recruitment or up to December 2021. Readiness was based on a checklist. Information from the study database; regular meetings and monitoring visits; and a questionnaire on laboratory operational aspects sent in May 2020 were used to assess continuity capacity. Compliance with seven basic requirements (readiness) and eight continuity requirements (continuity capacity) was scored (1 = compliant, 0 = not compliant) and totaled to classify readiness and continuity capacity as very limited, limited, moderate or high. Experiences, challenges, and enablers of the implementation process are also described. Seven of 12 laboratories had high readiness, three moderate readiness, and of two laboratories new to HPV testing, one had limited readiness and the other very limited readiness. Two of seven laboratories with high readiness also showed high continuity capacity, one moderate continuity capacity, and the other four showed limited continuity capacity since they could not maintain good quality HPV testing over time. Among three laboratories with moderate readiness, one kept moderate continuity capacity and two reached high continuity capacity. The two laboratories new to HPV testing achieved high continuity capacity. Based on gained expertise, five laboratories have become part of national screening programs. High readiness of laboratories is an essential part of effective implementation of HPV testing. However, high readiness is insufficient to guarantee HPV testing high continuity capacity, for which a "culture of quality" should be established with regular training, robust monitoring and quality assurance systems tailored to local context. All efforts to strengthen HPV laboratories are valuable and crucial to guarantee effective implementation of HPV-based cervical screening.

Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus.

Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH. In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher. Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%-93.6%) and 89.7% (83.0%-96.5%), respectively, and specificities of 72.9% (67.3%-78.5%) and 75.0% (69.5%-80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82-.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02-1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01-1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90-1.003]). Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing.

HPV-Based Screening with Cytologic Triage. Results of an Opportunistic Screening Protocol in Barcelona, Spain

HPV-Based Screening with Cytologic Triage. Results of an Opportunistic Screening Protocol in Barcelona, Spain

HPV-genotyping versus conventional cervical cytology as a screening method to detect dysplastic cervical epithelial changes

The world health organization (WHO) called for coordinated global action in 2018 to eliminate cervical cancer, ensuring that every woman is screened and treated for precancerous lesions (World Health Organization. Cervical cancer: an NCD we can overcome. Geneva, 2018. http://www.who.int/director-general/speeches/detail/cervical-cancer-an-ncd-we-can-overcome.tegy). Cytology-based screening has been for decades the conventional method of screening. Ancillary techniques have been added like immunocytochemistry with P16/Ki67 and L1-Capsid, but these methods require maintenance of complex infrastructure and highly trained personnel as well as relatively short screening intervals. HPV-based screening method to detect high-risk groups is a faster and automated method, which does not need morphologically highly qualified personal with high social costs. In the study, we have focused on the distribution of cervical lesions in the age groups with concordance of detection HPV high-risk subtypes (HPV-HR) and on the safety of the screening method. In the Institute for Pathology and Cytology-Schuettorf-Leer-Germany 146.800 samples of women from the age of and above 35 years were analyzed between the beginnings of 2020 until the beginning of 2021. 63.710 cases under 35 years old were analyzed. The samples were processed for both conventional cytological techniques and for molecular detection and subtyping of HPV-HR according to the advice and measurements of BD-manufacture. In this study, we have studied the histopathological results (Table 2) after colposcopy according to the age subgroups. The histopathological results were subdivided into no dysplasia, cervical intraepithelial neoplasia I (CIN I), cervical intraepithelial neoplasia II (CIN II), cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (Sq.c.c), adenocarcinoma in situ (AIS), endometrial carcinoma, endocervical adenocarcinoma and cases without biopsy during the colposcopy (COB). We have used the muenchener classification III (Table 3) as a subgrading system for the cytological specimens. The frequency of detecting HPV56/59/66 is higher as detecting HPV-16 and HPV18 in age groups under 35 years old, 41–50 years old and 51–60 years old. HPV16 is detected higher in age groups 35–40 years old and above 60 years. The incidence of high squamous intraepithelial lesions (CIN II and III) is 0.92% in age group 35–40 years, 0.54% in age under 35 years, 0.59% in age group 41–50 years old, 0.35% in age group 51–60 years old and 0.15% in age group above 60 years old. There is no significance (p value = 0.4060). Low grade cervical lesions (CIN I) were 0.13% (< 35 Ys), 0.35% (35–40 Ys), 0.36% (41–50 Ys), 0.25% (51–60 Ys) and 0.098% (> 60Y s), which was statistically significant (p value = 0.04,0.60). Without dysplasia 0.19% (< 35 Ys), 0.5% (35–40 Ys), 0.56% (41–50 Ys), 0.51 (51–60 Ys) and 0.26% (> 60 Ys). There is no significance between occurrence of cervical dysplasia and without dysplasia despite of detection of HPV-HR subtypes (p value = 0.1754). The only use of HPV-subtyping is not a secure method and a protective way for women. There are worldwide many HPV-positive cases, which have been psychologically impaired with higher costs, although they have no cervical epithelial changes during the HPV-infection. There are many HPV-negative cases, in some studies up to 13% of cases, which develop cervical cancer. We have the opinion and are convinced that the screening should be both morphologically via cytological examination and may be with adding immunocytochemistry to detect the really dysplastic cervical lesions. HPV-subtyping may be added every three years to detect the concomitant subtype.

HPV screening in the urine of transpeople - A prevalence study.

SummaryBackgroundThere is limited data on human papillomaviruses (HPV) prevalence in transpeople due to low acceptance rate of screening methods. HPV tests from self-collected urine are gender-neutral, have a high acceptance, and have a comparable accuracy in females to clinician-collected samples. The aim of this study was to evaluate both the HPV prevalence in the urine in a large cohort of 200 transpeople with common risk profiles and the acceptability of such screening method.MethodsThe study was conducted at the outpatient clinic for transpeople at the Department of Obstetrics and Gynaecology, Medical University of Vienna, Austria. 200 transpeople have been enrolled between May and October 2021. Inclusion criteria were gender identity dysphoria, age over 18 years, and adequate language skills.Subjects were asked to answer a survey concerning gender identity, established risk factors for HPV infections as well as their preference regarding urine or provider-collected cytology-/HPV-based screening, and to provide a urine sample. Five patients not able to provide urine were excluded. HPV genotyping was performed using a validated multiplex real-time PCR assay, which simultaneously detects 28 HPV genotypes. This trial is registered at ClinicalTrials.gov, NCT04864951.FindingsOverall HPV positivity was 19·0% (37/195), 24·2% in female to male, 11·8% in male to female, 26·3% in genderqueer/non binary/other subjects, 27·9% in subjects currently having a cervix, and 26·0% in subjects born with cervix. Independent of gender reassignment surgery, being born with a cervix was associated with a higher risk of HPV infections (p = 0·008), yet 42·3% (44/104) have never attended cervical cancer screening. Overall, 79·0% (154/195) of transpeople would prefer urine HPV tests to provider-collected HPV screening.InterpretationHPV testing in self-collected urine samples provides a unique opportunity for screening of this hard-to-reach population and should be evaluated in further studies.FundingNone.