Five-year evaluation of Anal Cancer Screening Program in Men Who Have Sex With Men with HIV at Two Academic Center Clinics.

BACKGROUND: Guidelines recommend annual anal cytology-based squamous cell carcinoma of anus (SCCA) screening for men who have sex with men (MSM) with HIV aged ≥35 years (eligible population). Recommended threshold for high resolution anoscopy (HRA) depends on its availability: low-threshold (any abnormal cytology) if availability is high, and high-threshold (High-Grade Squamous Intraepithelial Lesion (HSIL) on cytology) if availability is low. METHODS: Retrospective chart review (2018-2022) at academic HIV clinics. We evaluate (i) 5-year uptake of cytology based SCCA screening in eligible population; (ii) estimate HSIL detection rate based on our current low-threshold criteria, and if high-threshold criteria were used for HRA referral. RESULTS: Of 432 eligible individuals, only 219 (50.7%) had at least one, and only 113 (26%) had >1 SCCA screening tests in a median followup of 4 years. N=74 (17.1%) of individuals had at least one abnormal anal cytology during follow-up, of which 56 (75.6%) received HRA. Increasing age (≥57 years) and history of smoking negatively correlated with ever receiving screening. Anal cytology (365 tests in 206 individuals) showed: 17.5% 'unsatisfactory', and 26.8% with any abnormal cytology (zero with HSIL) triggering HRA referral. Only 34 individuals (7.8% of screening eligible) were ever detected with HSIL. Strictly using high-threshold criterion for HRA referral would have led to no HRA or HSIL detection. CONCLUSIONS: We noted poor uptake of screening over time, particularly in older age groups. Importantly, anal cytology performed poorly as a triage test for HRA referral: high rates of 'unsatisfactory' samples and low sensitivity for detecting HSIL.

Human papillomavirus vaccine to prevent CIN3 or worse (CIN3+): A nationwide case-control study in Japan.

An increase in cervical cancer incidence has been reported in Japan. The Ministry of Health, Labor, and Welfare of Japan has resumed the active recommendation of regular HPV vaccines in 2022. In Japan, the preventive effect of CIN3+ in the real world has not yet been demonstrated in age-adjusted cohort or case-control studies. This study aimed to estimate the effect of the HPV vaccine against CIN3+ in Japanese women. This nationwide case-control study from April 2013 to March 2020 targeted women aged 20-26 years old at the time of cervical screening. We compared HPV vaccination exposure between those with abnormal and those with normal cytology. Abnormal cytology was classified into cervical intraepithelial neoplasia (CIN)1+, CIN2+, and CIN3+. We calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 -OR) × 100. A total of 2790 cases and 13,990 controls (one-to-five matching) were eligible in 37 municipalities in Japan. In this study, 61 CIN3 (2.2%) and 10 squamous cell carcinomas (SCC) (0.4%) were found. The OR for CIN3+ versus controls was 0.14 (95% CI, 0.03-0.75), equating to a vaccine effectiveness of 86%. Of the 10 patients who had SCC none were vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in CIN3+ among women who did versus those who did not receive HPV vaccination.

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

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

A Review of Immunotherapy for Head and Neck Cancer.

The introduction of immune checkpoint inhibitors (ICIs) to oncological care has transformed the management of various malignancies, including head and neck squamous cell carcinoma (HNSCC), offering improved outcomes. The first-line treatment of recurrent and malignant HNSCC for many years was combined platinum, 5-fluorouracil, and cetuximab. Recently, the ICI pembrolizumab was approved as a first-line treatment, with or without chemotherapy, based on tumor and immune cell percentage of programmed-death ligand 1 (PD-L1). Multiple head and neck (HN) cancer trials have subsequently explored immunotherapies in combination with surgery, chemotherapy, and/or radiation. Immunotherapy regimens may be personalized by tumor biomarker, including PD-L1 content, tumor mutational burden, and microsatellite instability. However, further clinical trials are needed to refine biomarker-driven protocols and standardize pathological methods to guide combined regimen timing, sequencing, and deescalation. Gaps remain for protocols using immunotherapy to reverse oral premalignant lesions, particularly high-risk leukoplakias. A phase II nonrandomized controlled trial, using the ICI nivolumab, showed a 2-y cancer-free survival of 73%, although larger trials are needed. Guidelines are also needed to standardize the role of dental evaluation and care before, during, and after immunotherapy, specifically in regard to oral immune-related adverse events and their impact on cancer recurrence. Standardized diagnostic and oral care coordination strategies to close these gaps are needed to ensure continued success of HN cancer immunotherapy.

Conventional cytology scheme: adherence and associated factors.

OBJECTIVES: This study analyzed adherence rates to conventional cytology and associated factors in a cohort of women at a health service provider institution in Medellin, Colombia. STUDY DESIGN: Observational cohort study with repeated measures. METHODS: Clinical and sociodemographic data were obtained from databases for screenings between January 2018 and December 2022. Adherence, defined as undergoing 1, 2, or 3 cytology tests according to national guidelines, was the outcome. Statistical analysis involved a Poisson model with robust errors to identify factors associated with adherence. RESULTS: In total, 26,445 women were included, with a median age of 25 years (IQR: 22-27). Adherence rate was 20.4%. Having just high school education (RR = 0.51; 95% CI: 0.49-0.55), a history of pregnancy (RR = 0.63; 95% CI: 0.54-0.75), and a history of sexually transmitted infections (RR = 0.88; 95% CI: 0.78-0.99) decreased adherence. Conversely, the human papillomavirus (HPV) vaccination history increased adherence (RR = 2.11; 95% CI: 1.60-2.80). CONCLUSION: It is vital to monitor cytology programs to improve demand-induced and spontaneous consultations. Diligent follow-up, focusing on patients with factors linked to low adherence, along with appointment reminders, can enhance adherence to the screening protocol.

Knowledge, attitude and perception of Italian dental students toward HPV-related oropharyngeal cancer and vaccination: a cross-sectional study.

BACKGROUND: Human papillomavirus (HPV) infection is a leading cause of oropharyngeal squamous cell cancer (OPSCC). This study aimed to carry out a Knowledge, Attitude and Perception survey on HPV infection, HPV+ OPSCC, and HPV vaccination among Italian dental students. METHODS: Through an online self-administered questionnaire consisting of 82 questions, data on dental students' sociodemographic characteristics, knowledge, attitudes and perceptions concerning HPV+ OPSCC, infection and vaccination were acquired. A statistical analysis, based on their year of attendance (early career, from 1st to 3rd year vs. late career, from 4th to 6th year) was also conducted. RESULTS: A total of 412 dental students completed the questionnaire. Knowledge of HPV+ OPSCC was reported by 61% of early-career students and 73% of late-career students, with high awareness of the HPV-OPSCC correlation in both groups (85% vs. 89%, respectively). The percentage of correct responses regarding HPV infection knowledge was 61% for early-career and 73% for late-career students, while vaccine knowledge was 70% and 78%, respectively. Over 90% of students acknowledged the dentist's role in educating patients about HPV and OPSCC, and attitudes toward discussing HPV and vaccination were positive. However, only about half would recommend the vaccine to either gender. Statistically significant differences were found between early- and late-career groups across all knowledge sections (p < 0.001), while no significant differences emerged for perception (p = 0.076) or attitude (p = 0.147). CONCLUSIONS: The study reveals encouraging results but highlights significant gaps in dental students' knowledge, perceptions, and attitudes toward HPV+ OPSCC, infection, and vaccination. Addressing these gaps through targeted education and training in dental curricula could improve HPV prevention awareness and patient education, ultimately enhancing public health outcomes.

[Current vaccination and immunization strategies in dermatology]. / Aktuelles zu Impfungen und Immunisierungsstrategien in der Dermatologie.

Vaccinations are an important pillar of public health. They have high benefits for individuals and society as a whole by specifically preventing or mitigating infectious diseases. In many cases, they offer benefits that go beyond protection against the disease in question, e.g., protective cardiovascular effects. Vaccination recommendations in Germany are drawn up by the Standing Committee on Vaccination (STIKO), while the European Medicines Agency (EMA) is responsible for the approval of vaccines in the EU. Vaccinations may be carried out by physicians regardless of their specialty. In dermatology, vaccinations against varicella (chickenpox), herpes zoster, and human papillomavirus are established. The development of vaccines against other dermatologically relevant diseases and cancer vaccines is the subject of intensive research. Particularly in the case of immunosuppression, the physician must also take into consideration which vaccinations are possible and useful or contraindicated. Type I or type IV allergies to components of vaccinations are very rare, but reactions at the injection site often occur as a dermatological side effect. Urticarial reactions are also possible, as does the worsening of underlying dermatological conditions such as psoriasis vulgaris.

Alterations in miRNA Expression and Their Role in the Pathogenesis of Cervical Cancer.

BACKGROUND: Cervical cancer has a high incidence and mortality rate, affecting more than half a million women in 2018. Its development is strongly related to high-risk HPV infection. After infection, several cellular molecules are affected, including microRNAs (miRNAs), which are the focus of our study. We aimed to investigate changes in microRNA expression associated with cervical cancer and analyze the biological significance of these changes induced by HPV proteins. METHODS: We analyzed transcriptome data retrieved from the NCBI website to investigate miRNA and gene expression in cervical cancer. We evaluated the alteration in expression of miRNAs and genes (between normal tissues and cervical cancer) using the GEO2R tool and selected those with significantly altered expression (p-value < 0.05). The target genes of miRNAs were predicted using the miRNA Pathway Dictionary Database. Subsequently, we created a network of biological pathways affected by miRNA deregulation using Cytoscape software and associated the altered miRNAs with the Hallmarks of Cancer using COSMIC v84. RESULTS: We identified 10 miRNAs and 82 target genes with significantly altered expression levels in cervical cancer that matched the predicted results. In addition, the deregulation of these genes causes changes in 52 biological pathways. These miRNAs affected pathways such as interferon signaling (miR-106b-5p and miR-1183), signaling by interleukins (miR-557, miR-106b-5p, miR-15a-5p, and miR-21-5p), oxidative stress-induced senescence (miR-557 and miR-15a-5p), cell cycle checkpoints (miR-557), transcriptional regulation by P53 (miR-557 and miR-15a-5p), and the exchange of oxygen and carbon dioxide in erythrocytes (miR-15a-5p). CONCLUSION: Alterations in miRNA expression play an important role in the pathogenesis of cervical cancer, affecting several biological pathways and Hallmarks of Cancer, such as immune system regulation, cell cycle regulation, and energy metabolism. Thus, their analysis can contribute to the development of diagnostic and prognostic biomarkers and more effective treatments for cervical cancer.

Early-Stage and Locally Advanced Cervical Cancer during Pregnancy: Clinical Presentation, Diagnosis and Treatment.

In this comprehensive review supported by clinical examples, the authors explore the topic of cervical cancer in pregnancy, with emphasis on potential pre-cancer progression, the possibility of coexisting preinvasive and invasive disease, and neoadjuvant chemotherapy. This manuscript addresses the challenges of managing cervical cancer in pregnant women with a pregnancy-preserving approach, including the importance of screening, the timing of surgery, and the impact of pregnancy on the course of the disease. The first case study illustrates the potential for a benign cervical lesion to transform into a malignant one during pregnancy and the possible coexistence of preinvasive lesions together with early-stage cervical cancer. It also questions the rationale behind the non-treatment of pregnant patients initially diagnosed with CIN 2/3 during pregnancy. The second presented clinical example shows the histologically confirmed response to neoadjuvant chemotherapy, resulting in a radiologically diagnosed FIGO stage IIA1 being downgraded to adenocarcinoma in situ in the histology report after surgery performed six weeks postpartum. The treatment of cervical cancer, which is becoming increasingly prevalent among pregnant women, and the necessity for an individualized diagnostic and therapeutic approach represent significant challenges for contemporary medicine. Discrepancies in therapeutic options proposed among centers within the same region lead to the conclusion that there is a need for centralization and unification of evidence-based management in referral centers with both high-level oncological and perinatal care.

Children's and parents' attitudes to and knowledge about HPV vaccination following a targeted information intervention.

The aim of this study was to investigate Swedish children's and parents' attitudes and knowledge about human papillomavirus (HPV) vaccination a year after gender-neutral HPV vaccination was introduced in Sweden's national immunization program (NIP). Additional information about HPV and vaccine was provided in the extended immunazation program. In total, 276 parents and 206 children from 22 School Health Services responded to a web-based survey. Results showed that half of the children and about a third of the parents received additional Public Health Agency information about HPV vaccination, and a majority were satisfied. Parents considered HPV vaccination being important for their children's health, and both children and parents considered it important to vaccinate all genders against HPV. Both children and parents rated school nurses as most reliable source of HPV vaccination information. Teachers were also a common source of HPV and HPV vaccination information for children. Further research among teachers in Sweden is needed to explore their knowledge and abilities to inform students and parents about HPV and vaccination.

Human Papillomavirus, Cervical Intraepithelial Neoplasia, and Quantitative Blood Loss at Delivery.

Studies using estimated blood loss show the association of either human papillomavirus (HPV) or cervical intraepithelial neoplasia (CIN) with postpartum hemorrhage (PPH). We study the association of HPV or CIN with either blood loss or PPH as measured by the more precise measure of quantitative blood loss (QBL). We retrospectively studied 2,334 peripartum women with a documented Pap smear prior to de- livery. The main predictor variable had categories for HPV and CIN as compared to normal cytology. Covariates included demographics, medical/surgical history, and pregnancy variables. Model 1 included the whole sample. Model 2 included only those with an operative vaginal delivery or a cesarean delivery. Outcome measures were QBL and PPH measured by QBL. We found in model 1 that those HPV positive and those with CIN were each not significantly associated with QBL. In model 2, those HPV positive were significantly associated with increased QBL (B = 0.11, SE = 0.05, p = 0.047), while CIN was not significantly associated with QBL. In model 1, those HPV positive and those with CIN were each not significantly associated with PPH. In model 2, those HPV positive were significantly associated with increased odds for PPH (OR:11.03, 9% CI:1.77, 68.74, p = 0.01) while CIN was not significantly associated with PPH. In conclusion, the presence of HPV was positively associated with an increase in the QBL and PPH at time of delivery for those with operative vaginal and cesarean deliveries. We suggest that clinicians take HPV results of Pap smears into consideration when considering a patient's risk of PPH.

Characterization of High-Risk-Other Human Papillomavirus Genotypes in Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, and Cervical Cancer.

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for HPV genotype determination by Roche Linear Array (Roche Diagnostics, North America). Then we randomly selected 76 cervical biopsy samples of HGSIL or cervical cancer with high-risk-other HPV or HPV unknown status from 2016 to 2022 for HPV genotype determination by next-generation sequencing. Results are reported as counts and frequencies. Results: In the 50 high-risk-other HPV Pap test samples, 21 genotypes of HPV were noted; the most common were 53 (n=6), 51 (n=6), and 59 (n=5). In the samples with HGSIL or cervical cancer, 16 HPV genotypes were detected; the most common were 16 (n=26), 58 (n=12), and 33 (n=8). Among the patients with HGSIL or cervical cancer, the 9-valent HPV vaccine provided coverage for all the HPV variants found in 88% of patients, partial coverage in 8% of patients, and no coverage in 4% of patients. Conclusion: The 3 most common HPV genotypes seen in our high-risk-other HPV Pap test samples are not covered by the 9-valent HPV vaccine. For the HGSIL and cancer samples, 88% of the samples had full HPV genotype coverage with the 9-valent HPV vaccine. This study highlights a presence of HPV that will not be protected by vaccination in a high-risk population.

Immunoinformatics approach for design novel multi-epitope prophylactic and therapeutic vaccine based on capsid proteins L1 and L2 and oncoproteins E6 and E7 of human papillomavirus 16 and human papillomavirus 18 against cervical cancer.

BACKGROUND: This study aimed to identify the optimal protein construction for designing a multi-epitope vaccine with both prophylactic and therapeutic effects against cervical cancer, utilizing an immunoinformatics approach. The construction process involved using capsid epitopes L1 and L2, as well as oncoproteins E5, E6, and E7 from human papillomavirus (HPV) types 16 and 18. METHODS: An experimental in silico analysis with an immunoinformatics approach was used to develop 2 multi-epitope vaccine constructs (A and B). Further analysis was then conducted to compare the constructs and select the one with the highest potential against cervical cancer. RESULTS: This study produced 2 antigenic, non-allergenic, and nontoxic multi-epitope vaccine constructs (A and B), which exhibited the ideal physicochemical properties for a vaccine. Further analysis revealed that construct B effectively induced both cellular and humoral immune responses. CONCLUSION: The multi-epitope vaccine construct B for HPV 16 and 18, designed for both prophylactic and therapeutic purposes, met the development criteria for a cervical cancer vaccine. However, these findings need to be validated through in vitro and in vivo experiments.

Rationale and design of the Self-TI Study protocol: a cross-sectional human papillomavirus self-testing pilot study among transgender adults in England.

INTRODUCTION: Persistent infection with high-risk human papillomavirus (HPV) is the causal agent of several cancers including cervical, anal and oropharyngeal cancer. Transgender men and transmasculine non-binary (TMNB) people with a cervix are much less likely to undergo cervical cancer screening than cisgender women. Transgender women and transfeminine non-binary (TWNB) people assigned male at birth may be at increased risk of HPV. Both TMNB and TWNB people face many barriers to HPV testing including medical mistrust due to stigma and discrimination. METHODS AND ANALYSIS: The Self-TI Study (Self-TI) is a pilot study designed to measure acceptability and feasibility of HPV self-testing among transgender and non-binary people in England. TMNB people aged 25-65 years, with at least 1 year of testosterone, and TWNB people, aged 18 years and over, are eligible to participate. Participants self-collect up to four samples: an oral rinse, a first void urine sample, a vaginal swab (if applicable) and an anal swab. TMNB participants are asked to have an additional clinician-collected cervical swab taken following their routine Cervical Screening Programme sample. TWNB people are asked to take a self-collection kit to perform additional self-collection at home and mail the samples back to the clinic. Acceptability is assessed by a self-administered online survey and feasibility is measured as the proportion of samples returned in the clinic and from home. ETHICS AND DISSEMINATION: Self-TI received ethical approval from the Research Ethics Committee of Wales 4 and ethical review panel within the Division of Cancer Epidemiology and Genetics at the US National Cancer Institute. Self-TI was coproduced by members of the transgender and non-binary community, who served as authors, collaborators and members of the patient and public involvement (PPI) group. Results of this study will be shared with the community prior to being published in peer-reviewed journals and the PPI group will help to design the results dissemination strategy. The evidence generated from this pilot study could be used to inform a larger, international study of HPV self-testing in the transgender and non-binary community. TRIAL REGISTRATION NUMBER: NCT05883111.

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009-2014.

Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009-2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV-1, and HSV-2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26-1.70; OR 1.09, 95% CI 1.05-1.13; OR 1.06, 95% CI 1.01 - 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29-1.77; OR 1.08, 95% CI 1.04-1.12; OR 1.05, 95% CI 1.01-1.10, respectively) after adjusting all relevant co-factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV-1 infection, while the relationship between HSV-2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years.

Investigating under-reported human papillomavirus genotypes in Grenadian women through self-sampling for cervical cancer screening.

Objective: To compare the adequacy, agreement, and acceptability of Papanicolaou testing (cytology) for cervical cancer screening using self-collected samples compared to physician-collected samples in Grenada in the Caribbean. Furthermore, the study identifies the human papillomavirus (HPV) genotypes present among asymptomatic women testing positive for HPV, the etiologic cause of cervical cancer. Methods: Participants were divided into two groups and two cervical samples were collected from the women in each group: a self-collected sample and a physician-collected sample. Cervical specimens were tested for cytology and HPV. HPV genotyping was performed on positive specimens. Results: Self-collected samples were adequate and in agreement with physician-collected samples, showing no difference between the two sampling methods. Oncogenic high-risk HPV genotypes were identified in cervical samples which were positive for atypical squamous cells and low-grade squamous intraepithelial lesions. The high-risk HPV genotypes found, notably HPV 45 and 53, differed from those most commonly reported. Although the commonly reported high-risk genotypes HPV 16 and 18 were found, so were 31, 33, 35, 52, 66, 68, and 82. Conclusions: Using self-collection facilitated the discovery of unexpected HPV genotypes among asymptomatic women in Grenada. These findings add new information to the literature regarding cervical cancer and neoplasia screening and HPV genotypes in the Caribbean. This genotype information may impact surveillance of women with low-grade lesions, HPV vaccine selection, and possibly further vaccine research. Research regarding HPV in Caribbean pathology samples of cervical neoplasia and cancer is needed.

Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3. / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

INTRODUCTION: Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. OBJECTIVE: To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). MATERIALS AND METHODS: Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. RESULTS: The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT <0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. CONCLUSION: The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT <0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

Performance of CADM1, MAL and miR124-2 methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea.

OBJECTIVE: WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples. DESIGN: Exploratory observational study. SETTING: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea. PARTICIPANTS: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal). PRIMARY AND SECONDARY OUTCOME MEASURES: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain. RESULTS: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%). CONCLUSION: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.

Variables that impact HPV test accuracy during vaginal self collection workflow for cervical cancer screening.

Vaginal self collection (SC) is safe and effective for human papillomavirus (HPV) testing and can increase cervical cancer screening coverage for underserved women. To better understand the impact of SC methodology on HPV test outcomes, empirical testing was conducted using different swab collection workflows. Deposition of the collection swab into resuspension buffer resulted in a 2.4-cycle reduction in threshold detection of human beta-hemoglobin during PCR when compared to "swirl-and-toss". In addition, reducing the swab resuspension volume from 10 mL to 3 mL resulted in a 2.6-cycle reduction in threshold detection of human beta-globin. A systematic literature search (01/01/2020 to 08/02/2023) of Ovid Medline and Embase, followed by data extraction and analysis, was conducted to further assess the impact of resuspension volume on performance following SC. HPV test performance for SC, relative to clinician collection (CC), was calculated for detection of cervical pre-cancer. Data were stratified by the resuspension volume ratio of SC to CC being either ≥ 1.0 or < 1.0. SC with a volume ratio of ≥ 1.0 and < 1.0 had a relative ≥ CIN2 sensitivity of 92.0 % (95 % CI: 88.0, 96.0) and 97.0 % (95 % CI: 94.0, 100), respectively. Taken together, these results suggest that SC conditions can be modified to optimize sample recovery and performance, as part of cervical cancer screening.

Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.