Human Papillomavirus Screening Research Articles

Enhanced cervical cancer and HIV interventions reduce the disproportionate burden of cervical cancer cases among women living with HIV: A modeling analysis.

Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied. Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021-2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV. Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% [Uncertainty Range (UR): 26-42%] in 2021 to 25% [19-34%] in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% [63-86%] to 58% [47-74%], but incidence remained 4.3-fold [3.3-5.7] that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 [3.7-7.3]. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 [3.6-7.6]), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 [1.9-3.4] in 2071. Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.

Concomitant Cervical and Anal Screening for Human Papillomavirus (HPV) – Worth the effort or waste of time?

Abstract Background Human papilloma virus (HPV) infection represents the most common sexually transmitted disease and a major risk factor for disease progression to anal cancer. Aims This study aimed to analyze the rate of concomitant anal dysplasia in a prospectively surveilled cohort of sexually active women. Methods This study represents a follow-up analysis of the AnusGynecology (ANGY) study (doi.org/10.3390/cancers14205096). This prospective, cross-sectional single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. Cervical / anal smears +/- biopsies if deemed necessary were performed by board-certified specialists during a single outpatient visit. All women with findings of either HPV or any type of dysplastic lesions on anal smears were offered follow-up in a specialized high-resolution anoscopy (HRA) outpatient clinic. Results Overall, 275 patients (mean age 42±12) were included. Among them, 102 (37%) had cervical high risk (HR)-HPV. Anal smear cytology was performed in 255 patients (93%), while 19 patients (7%) underwent anal biopsy during the combined visit. In total, HPV was (incidentally) revealed in 91 patients (33%) on anal smears, while any degree of anal dysplasia was found in 30 patients (11%), 6 if which were high-grade squamous intraepithelial lesions (H-SIL). Furthermore, 10 out of 19 biopsies were positive (3 H-SIL lesions). Only half (48/93, 52%) of women agreed to undergo the recommended specialized follow-up evaluation. Of them, 18 (38%) were diagnosed with dysplastic lesions (9 L-SIL and H-SIL, respectively) on biopsies, while the remaining visits revealed no abnormalities. Conclusion The present study revealed a significant number of dysplastic lesions in women willing to undergo specialized proctologic evaluation after abnormal findings on initial screening. Close follow-up of these women is hence strongly recommended.

Concomitant human papillomavirus (HPV) vaccination and screening for elimination of HPV and cervical cancer.

HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a population-based trial of this strategy to reduce the incidence of HPV. All 89,547 women born 1994-1999 and resident in the capital region of Sweden were personally invited to concomitant HPV vaccination and HPV screening with 26,125 women (29.2%) enrolled between 2021-05-03 and 2022-12-31. Baseline HPV genotyping of cervical samples from the study participants finds, compared to pre-vaccination prevalences, a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, some decline for cross-protected HPV types but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicts that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 62-64% in 3 years. Baseline results are prevalences of HPV infection, validated transmission model projections, and power estimates for evaluating HPV incidence reductions at follow-up (+/-0.1% with 99.9% confidence). In conclusion, concomitant HPV vaccination and HPV screening appears to be a realistic option for faster cervical cancer elimination. Clinicaltrials.gov identifier: NCT04910802; EudraCT number: 2020-001169-34.

Human Papillomavirus Vaccination Hesitancy, Screening Disparities, and Associated Factors Among Sexual and Gender Minority Women: A Systematic Review of Global Literature [ID 2683547

INTRODUCTION: Human papillomavirus (HPV) ranks as the most prevalent sexually transmitted infection globally, with a significant association with cervical cancer in cervix-having individuals. Understanding the epidemiological patterns of HPV vaccination rates and behaviors within the context of sexual and gender minority (SGM) women is essential in identifying factors hindering the initiation of HPV vaccination and screening. METHODS: A systematic review was conducted by searching five databases (PubMed, CINAHL, Embase, Web of Sciences, MedLine). Eligibility criteria included the following: reported HPV vaccination or screening outcomes, conducted among SGM women, data collected since 2010. All studies were independently screened and synthesized following PRISMA guidelines. Of 44 items, 13 studies met the criteria. RESULTS: Sexual and gender minority women reported substantial HPV vaccine hesitancy and decreased screening practices compared to their non-SGM peers, with the degree of vaccine hesitancy and delayed screening varying among bisexual, lesbian, and transgender individuals. Individual factors associated with HPV vaccine hesitancy and decreased screening include socioeconomic status, vaccination awareness, and SGM identity. Meanwhile, interpersonal and structural factors include community biases, family support, lack of provider LGBTQ+ health education, and structural racism. CONCLUSION: Sexual and gender minority women experience a substantial health care disparity surrounding HPV vaccination hesitancy and screening status. Results from this study substantiate the need for the standardization of health care practice, individual patient vaccine counseling, and the expansion of sexual and gender minority health training at all tiers of medical education. Furthermore, additional disaggregated research is needed to understand the unique health circumstances of bisexual, lesbian, and transgender individuals, as the current research landscape fails to capture the community’s health needs.

Cost-effectiveness of single-visit cervical cancer screening in KwaZulu-Natal, South Africa: a model-based analysis accounting for the HIV epidemic.

Women living with human immunodeficiency virus (WLHIV) face elevated risks of human papillomavirus (HPV) acquisition and cervical cancer (CC). Coverage of CC screening and treatment remains low in low-and-middle-income settings, reflecting resource challenges and loss to follow-up with current strategies. We estimated the health and economic impact of alternative scalable CC screening strategies in KwaZulu-Natal, South Africa, a region with high burden of CC and HIV. We parameterized a dynamic compartmental model of HPV and HIV transmission and CC natural history to KwaZulu-Natal. Over 100 years, we simulated the status quo of a multi-visit screening and treatment strategy with cytology and colposcopy triage (South African standard of care) and six single-visit comparator scenarios with varying: 1) screening strategy (HPV DNA testing alone, with genotyping, or with automated visual evaluation triage, a new high-performance technology), 2) screening frequency (once-per-lifetime for all women, or repeated every 5 years for WLHIV and twice for women without HIV), and 3) loss to follow-up for treatment. Using the Ministry of Health perspective, we estimated costs associated with HPV vaccination, screening, and pre-cancer, CC, and HIV treatment. We quantified CC cases, deaths, and disability-adjusted life-years (DALYs) averted for each scenario. We discounted costs (2022 US dollars) and outcomes at 3% annually and calculated incremental cost-effectiveness ratios (ICERs). We projected 69,294 new CC cases and 43,950 CC-related deaths in the status quo scenario. HPV DNA testing achieved the greatest improvement in health outcomes, averting 9.4% of cases and 9.0% of deaths with one-time screening and 37.1% and 35.1%, respectively, with repeat screening. Compared to the cost of the status quo ($12.79 billion), repeat screening using HPV DNA genotyping had the greatest increase in costs. Repeat screening with HPV DNA testing was the most effective strategy below the willingness to pay threshold (ICER: $3,194/DALY averted). One-time screening with HPV DNA testing was also an efficient strategy (ICER: $1,398/DALY averted). Repeat single-visit screening with HPV DNA testing was the optimal strategy simulated. Single-visit strategies with increased frequency for WLHIV may be cost-effective in KwaZulu-Natal and similar settings with high HIV and HPV prevalence.

Performance evaluation of a self-administered point-of-care test for anal HPV screening in PrEP users: data from a community-based PrEP service.

In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its feasibility. We enrolled PrEP users from a local community-based PrEP service. Each participant self-collected an anal swab to test anal HPV with a PCR POCT capable of detecting 14 high-risk HPV genotypes. Anonymous questionnaires on self-sampling feasibility were completed. Participants were then referred to local clinics to undergo standard viral genotyping. Concordance between POCT and gold-standard test was measured with absolute agreement and Cohen's kappa. Receiver operating characteristic (ROC) curves were used to calculate POCT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). 179 subjects got a valid POCT result, most of them men (98.3%) and men who have sex with men (90.4%). 68.2% tested positive for at least one high-risk HPV genotype on POCT. 150 feasibility questionnaires were collected: 92.7% of compilers found the self-swab easy to perform. For 178 subjects, a gold-standard test valid result was also available: 77% tested positive for at least one high-risk HPV genotype. The median time elapsed between the two tests was 9.8 months, due to COVID-19-related service interruptions. Agreement between POCT and gold-standard test was 79.3% (Cohen's kappa=0.49). POCT showed a sensitivity of 81.0%, a specificity of 73.8%, a PPV of 91.0% and an NPV of 54.4%. POCT showed a moderate agreement with gold-standard test and a discrete sensitivity and specificity, suggesting that it could be a useful and feasible additional tool for HPV screening, especially in low-resource and community-based settings.

Analysis of the application value of HPV mRNA and DNA detection in early screening of cervical lesions

Aim: At present, COBAS human papillomavirus (HPV) and Aptima HPV screening are widely used to detect HPV infection. In this study, we compared and analyzed the positive rates of DNA and mRNA (n = 10,128 women). Methods: After HPV screening, colposcopy was performed. Subsequently, pathological analysis was conducted on the screening results. Results: In Aptima HPV 16 group, the proportion of pathological lesions ≥CIN2 was 32.69%, while in COBAS HPV group, it was 24.18% (p < 0.05). Aptima HPV other risk types and COBAS HPV other risk types, the proportion of cases ≥CIN2 was 12.42 and 5.79%, respectively (p < 0.001). Conclusion: The results illustrated that the Aptima HPV test detects more accurately clinically relevant lesions than the COBAS test.

Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus–Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study

Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer–HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus–associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution’s dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus–associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.

The indirect costs of human papillomavirus-related cancer in Central and Eastern Europe: years of life lost and productivity costs

Background Human papilloma virus (HPV) is a common cause of several types of cancer, including head and neck (oral cavity, pharynx, oropharynx, hypopharynx, nasopharynx, and larynx), cervical, vulval, vaginal, anal, and penile cancers. As HPV vaccines are available, there is potential to prevent HPV-related disease burden and related costs. Method A model was developed for nine Central Eastern European (CEE) countries (Bulgaria, Croatia, Czechia, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia). This model considered cancer patients who died from 11 HPV-related cancers (oropharynx, oral cavity, nasopharynx, hypopharynx, pharynx, anal, larynx, vulval, vaginal, cervical, and penile) in 2019. Due to data limitations, Bulgaria only included four cancer types. The model estimated the number of HPV-related deaths and years of life lost (YLL) based on published HPV-attributable fractions. YLL was adjusted with labor force participation, retirement age and then multiplied by mean annual earnings, discounted at a 3% annual rate to calculate the present value of future lost productivity (PVFLP). Results In 2019, there were 6,832 deaths attributable to HPV cancers resulting in 107,846 YLL in the nine CEE countries. PVFLP related to HPV cancers was estimated to be €46 M in Romania, €37 M in Poland, €19 M in Hungary, €15 M in Czechia, €12 M in Croatia, €10 M in Serbia, €9 M in Slovakia, €7 M in Bulgaria and €4 M in Slovenia. Conclusions There is a high disease burden of HPV-related cancer-related deaths in the CEE region, with a large economic impact to society due to substantial productivity losses. It is critical to implement and reinforce public health measures with the aim to reduce the incidence of HPV-related diseases, and the subsequent premature cancer deaths. Improving HPV screening and increasing vaccination programs, in both male and female populations, could help reduce this burden.

Human Papillomavirus and Its Association With Cervical Cancer: A Review.

The human papillomavirus (HPV) belongs to the Papillomavirus family and is considered a non-enveloped virus. HPV affects individuals by causing both benign and malignant lesions. We aim to define HPV and its important characteristics, explain the relation between HPVs and cervical cancer, review its prevalence among Saudi women and their awareness of screening and prevention of cervical cancer, and focus on the importance ofHPVvaccination. The persistence of HPV infection is the most important risk factor for the development of cervical cancer.HPVs cannot be cultured, and the identification of the virus is dependent on a variety of techniques, including immunology, serology, and molecular biology. Cervical cancer is the fourth most prevalent form of cancer in women worldwide, while it is considered the 12th type of cancer that affects Saudi women. Unfortunately, many studies have shown a lack of awareness regarding HPV infection, screening, and vaccination among the Saudi population in general, as well as among Saudi healthcare professionals. The HPV vaccine has a potent role in preventing people from getting infected with the virus, despite some previous clinical trials assessing the outcomes of therapeutic HPV vaccinations showing unsatisfactory results. While there is no doubt about the benefits of vaccines and their role in reducing the incidence of HPV infectious diseases, there are discrepancies in the evaluation of the safety of the HPV vaccine.In conclusion, HPV is an essential etiology of cervical cancer, and the expansion of public awareness about protective methods and threat factors associated with HPV infection is highly important.

Cervical Squamous Intraepithelial Lesions: A Comparison of Diagnostic Approaches

Aim. To compare the effectiveness of Papanicolaou test, screening for oncogenic human papillomavirus (HPV) strains, and colposcopy in diagnosis of cervical squamous intraepithelial lesions and cervical cancer.Materials and Methods. We conducted a retrospective study which included 101 patients aged 21-65 years (mean age 36.9 ± 8.2 years). All patients underwent cytological examination, screening for 14 high-risk HPV types, and colposcopy. The prognostic value of the methods was calculated using standard formulas for determining the sensitivity, specificity, and prognostic value of positive and negative results. Cervical biopsy was accepted as the gold standard.Results. Among the examined women (n = 101), high-risk HPV types were detected in 78 women (77.2%). According to the results of cytological examination, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and cancer were detected in 24 (23.8%), 24 (23.8%), 22 (21.7%), and 2 (2%) cases, respectively. Abnormal colposcopy results of the 1st and 2nd degree were found in 33 (32.7%) and 51 (50.5%) women, respectively. The highest sensitivity in the diagnosis of low-grade squamous intraepithelial lesion was demonstrated by colposcopy (81.3%), whilst HPV testing and cytological examination had lower sensitivity values (75.0% and 58.3%, respectively). However, HPV testing had the highest sensitivity (85.7%) in diagnosis of high-grade squamous intraepithelial lesion and cervical cancer, whereas colposcopy and Papanicolaou test were behind (82.9% and 63.6%, respectively).Conclusion. Detection of high-risk HPV types has a high sensitivity in detecting both low- and highgrade squamous intraepithelial lesions and cervical cancer.

The current state of the problem of cervical screening

the article summarizes the issue of prevention of cervical cancer - the most common disease associated with the human papillomavirus (HPV). The main goal of this study is to generalize the etiology of cervical cancer, to note unique opportunities for its prevention, as well as to develop screening tests for HPV as one of the most effective strategies. Explore how current HPV diagnostics detect E6/E7 DNA or mRNA in cervical/vaginal specimens using molecular technologies. To find out whether HPV screening tests are more sensitive than cytology or visual examination with acetic acid as the primary screening method, and even more clinically valuable for detecting subtle cytological changes as a hybrid test. Through a detailed study of literature sources, their systematization and approaches to solving the problem, it was found that technical and laboratory capabilities are very limited in underserved places, so women have to travel long distances and make some efforts to prevent and treat cervical cancer. The relevance of the study of this pathology lies in the fact that cervical cancer is a serious public health problem and is the fourth most common cancer in women worldwide, accounting for about 604,000 new cases every year. And the practical implementation of an HPV screening program can face many problems, and measures must be taken to overcome these problems without compromising the detection of the disease. These measures could include reducing the frequency of screening using the WHO global strategy to offer HPV screening tests at ages 35 and 45, implementing high-throughput testing technology, and improving access to vaginal HPV screening tests for women in remote areas. Improving informational education for those who do not want to undergo a gynecological examination. Another important strategy is to implement a see-and-treat approach using a healthcare delivery platform that requires limited laboratory technician skills. In addition, the development and large-scale implementation of more specific HPV testing technologies that are much cheaper and easier to use in a non-laboratory setting than currently available options should be a priority for underserved facilities. At the same time, there is a need to develop and initiate implementation of an affordable and readily available intermediate or secondary test with optimal specificity to triage or separate clinically insignificant HPV infections that do not require colposcopy. The results of this study may be of interest to primary care physicians, gynecologists, oncologists, and therapists.

Performance of a vaginal self-collection device versus clinician collected cervical samples for the detection of high-risk human papillomavirus

ObjectiveScreening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. MethodsA cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. ResultsOverall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. ConclusionThe Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

Therapeutic Effect Analysis of Cervical Cancer Vaccine

Cervical cancer is a very widespread carcinogenic condition that poses a significant threat to women's health. The primary cause of this condition is mostly linked to persistent infection with high-risk strains of human papillomavirus (HPV), which are recognized for their ability to promote the development of cancer. Due to HPV infection, both therapeutic and preventative HPV vaccinations have been developed. Therapeutic vaccines can eradicate viruses and virus-infected cells by stimulating cellular immunity. Notwithstanding the availability of preventive HPV vaccinations, HPV screening, surgery, radiotherapy, and chemotherapy, the therapeutic effect on cervical cancer patients is limited. Therefore, therapeutic vaccines have emerged as a new treatment option. The cancer-causing proteins E6 and E7, which are consistently detected in cervical cancer and precancerous lesions, are crucial in the progression and sustenance of cervical cancer. Consequently, these cancer-causing proteins present an encouraging opportunity for the research and creation of therapeutic cervical cancer vaccines. The multiple therapeutic vaccines against cervical cancer will be briefly discussed in this article, including their mechanisms, development methods, and clinical effects.

Abstract 6082: Rapid on-site nucleic acid detection using CRISPR and digital signal processing for portable and integrated cervical cancer screening in low resource settings

Abstract Addressing the global disparity in cancer care necessitates the development of rapid and affordable nucleic acid (NA) testing technologies. This need is particularly critical for cervical cancer. Molecular detection of human papillomavirus (HPV) has emerged as a highly accurate screening method, surpassing traditional Pap smears. However, implementing this transition in low- and middle-income countries has been challenging due to the high costs and centralized facilities required for current NA tests. Here, we present CreDiT (CRISPR Enhanced Digital Testing), an advanced diagnostic system for rapid, on-site NA detection. CreDiT integrates two major technical breakthroughs: i) a one-pot CRISPR strategy that simultaneously amplifies both target NAs and analytical signals, and ii) a robust fluorescent detection method based on digital communication (encoding/decoding) technology. These innovations enhance CreDiT's practical utility, offering a rapid assay (<35 minutes) that integrates NA extraction and detection in a single streamlined workflow. Furthermore, CreDiT's straightforward probe design enables easy incorporation of new NA targets, while its compact device provides robust signal detection. We adapted CreDiT for point-of-care HPV screening by designing probes for high-risk HPV genes (HPV16, HPV18, HPV45, HPV31, HPV33, HPV58) and oncoprotein mRNAs (E6, E7, p16INK4a) and developing a portable CreDiT device capable of processing 12 samples. CreDiT demonstrated sensitive detection of cell-derived HPV DNA targets down to single copies and accurately identified HPV types in every clinical cervical brushing specimen (n = 121) we tested. This technology has the potential to facilitate prompt and reliable triaging of high-risk HPV, overcoming pathology bottlenecks and circumventing geographical and socioeconomic barriers to effective cervical cancer screening in resource-limited regions. This work has spearheaded recent screening research efforts in Uganda and Ghana. Citation Format: Chang Yeol Lee, Hyunho Kim, Hanna Lee, Thomas Randall, Amy Ly, Hakho Lee, Cesar M. Castro. Rapid on-site nucleic acid detection using CRISPR and digital signal processing for portable and integrated cervical cancer screening in low resource settings [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 6082.

A multiplex RPA-CRISPR/Cas12a-based POCT technique and its application in human papillomavirus (HPV) typing assay

Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary and initiating factor for cervical cancer. With over 200 identified HPV types, including 14 high-risk types that integrate into the host cervical epithelial cell DNA, early determination of HPV infection type is crucial for effective risk stratification and management. Presently, on-site immediate testing during the HPV screening stage, known as Point of Care Testing (POCT), remains immature, severely limiting the scope and scenarios of HPV screening. This study, guided by the genomic sequence patterns of HPV, established a multiplex recombinase polymerase amplification (RPA) technology based on the concept of “universal primers.” This approach achieved the multiple amplification of RPA, coupled with the CRISPR/Cas12a system serving as a medium for signal amplification and conversion. The study successfully constructed a POCT combined detection system, denoted as H-MRC12a (HPV—Multiple RPA—CRISPR/Cas12a), and applied it to high-risk HPV typing detection. The system accomplished the typing detection of six high-risk HPV types (16, 18, 31, 33, 35, and 45) can be completed within 40 min, and the entire process, from sample loading to result interpretation, can be accomplished within 45 min, with a detection depth reaching 1 copy/μL for each high-risk type. Validation of the H-MRC12a detection system’s reproducibility and specificity was further conducted through QPCR on 34 clinical samples. Additionally, this study explored and optimized the multiplex RPA amplification system and CRISPR system at the molecular mechanism level. Furthermore, the primer design strategy developed in this study offers the potential to enhance the throughput of H-MRC12a detection while ensuring sensitivity, providing a novel research avenue for high-throughput detection in Point-of-Care molecular pathogen studies.

Strategies to Increase Cervical Cancer Screening With Mailed Human Papillomavirus Self-Sampling Kits: A Randomized Clinical Trial

ABSTRACT In the United States, adherence for cervical cancer screening decreased from 86% to 77% between 2005 and 2019. Over 50% of cervical cancers are diagnosed in individuals overdue for screening, and promoting access and adherence is essential. Unlike traditional Papanicolaou testing, human papillomavirus (HPV) screening can use self-collected samples, which have comparable sensitivity and specificity to clinician-collected samples. Self-collecting has been shown to increase screening adherence, possibly by circumventing important barriers such as scheduling clinic appointments and negativity about pelvic examinations. Despite this, most individuals in prior studies remained unscreened with low follow-up of HPV-positive results, and kit uptake among populations that are screening adherent or have unknown screening history is unknown. The STEP trial (self-testing options in the era for primary HPV screening for cervical cancer) was a parallel, single-blind, randomized clinical trial comparing cervical cancer screening completion across groups of individuals with due (screening-adherent), overdue, or unknown screening history. Participants were randomized to traditional care (patient reminders and clinician electronic health record [HER] alerts), education (usual care plus educational materials about screening), direct mail (traditional care plus educational materials plus a mailed HPV self-collection kit), or to opt in (traditional care plus educational materials plus the option to request a self-collection kit). Patients were identified using the Kaiser Permanente Washington HER and administrative claims. Eligible participants were females aged 30 to 64 years with current Kaiser Permanente Washington insurance and primary care, intact cervix, who were either due or overdue for screening. The primary study outcome was screening completion within 6 months after randomization, which could be done either in clinic or using the self-collection kit. Modified Poisson regression was used to estimate relative risk (RR) of screening completion for the direct-mail and opt-in groups, relative to the education group. A total of 32,771 participants were randomized between November 2020 and January 2022, of which 13,356 were due for screening, 8682 were overdue, and 10,733 had unknown screening history. Of those due for screening, the RR for screening completion was 1.30 (95% confidence interval [CI], 1.23–1.36; absolute difference, 14.1% [95% CI, 11.2%–16.9%]) for direct mail and 1.07 (95% CI, 1.02–1.12; absolute difference, 3.5% [95% CI, 1.2%–5.7%]) for the opt-in group compared with education. Of those overdue for screening, the RR for screening completion was 1.90 (95% CI, 1.68–2.16; absolute difference 16.9% [95% CI, 13.8%–20.0%]) for direct mail compared with education. Of those with unknown screening history, the RR for screening completion was 1.14 (95% CI, 1.03–1.25; absolute difference 2.2% [95% CI, 0.5%–3.9%]) for the opt-in group compared with education. The results of this randomized controlled trial showed that directly mailing HPV self-collection kits increased cervical cancer screening by over 14% compared with education alone. The effect was similar between participants that were due or overdue for screening, and an opt-in approach was found to minimally increase screening.

Screening for High-Risk Human Papillomavirus Reveals HPV52 and HPV58 among Pediatric and Adult Patient Saliva Samples.

Previous research has demonstrated that the human papillomavirus (HPV) can infect a wide range of human tissues, including those within the oral cavity. High-risk oral HPV strains have been associated with the development and progression of oral cancers, including oral squamous cell carcinomas. Although many studies have examined the prevalence of the high-risk strains HPV16 and HPV18, far fewer have assessed the prevalence of other high-risk HPV strains. An approved study protocol was used to identify HPV52 and HPV58 among clinical samples (n = 87) from a saliva biorepository. Quantitative polymerase chain reaction (qPCR) and validated primers for HPV52 and HPV58 were used to facilitate this screening. This screening demonstrated that a total of n = 4/45 or 8.9% of adult saliva samples harbored high-risk HPV52, and n = 2/45 or 4.4% tested positive for high-risk HPV58. In addition, a total of n = 6/42 or 14.3% of the pediatric saliva samples tested positive for high-risk HPV, including n = 5/42 or 11.9% with HPV52 and n = 3/42 or 7.1% for HPV58. These data demonstrate the presence of the high-risk oncogenic HPV52 and HPV58 strains among both adult and pediatric clinical patient samples. More detailed longitudinal research must be conducted to determine whether this prevalence may be increasing or decreasing over time. In addition, these data strongly support public health prevention efforts, such as knowledge and awareness of the nine-valent HPV vaccine covering additional high-risk strains, including HPV52 and HPV58.

'I was able to make a better decision about my health.' Wāhine experiences of colposcopy at a marae-based health clinic: A qualitative study.

Equitable access to colposcopy services is required if we are to realise the benefit of the introduction of human papilloma virus (HPV) screening in Aotearoa New Zealand. We piloted a community colposcopy clinic, co-located at an urban marae health clinic. To describe the experiences of wāhine (women) attending the marae-based colposcopy clinic. An in-depth reflexive thematic analysis from 34 people's accounts was undertaken. Five themes were identified from the experiences of wāhine attending the clinic. Three themes related to how having a local clinic supported access: everyone was welcoming and friendly, the environment was familiar and non-clinical and the clinic was accessible. The fourth theme related to how this contributed to agency. A fifth theme relates to wāhine views about informing the ongoing provision of colposcopy services. The experiences reflected the principles and values practised at the marae health clinic. Wāhine described feeling cared for as soon as they entered the clinic. As the clinic was local, and for some based at their marae, it was a known space where they knew the experience would be safe. Whānau were welcome with spaces for children to play. Being local meant there were fewer logistics to manage, all of which supported access. Prioritising wāhine through the provision of culturally safe and accessible colposcopy is feasible. It has the potential to contribute to the elimination of cervical cancer in Aotearoa, New Zealand.

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.