High-risk Human Papillomavirus Types Research Articles

Lineage Replacement and Genetic Changes of Four HR-HPV Types during the Period of Vaccine Coverage: A Six-Year Retrospective Study in Eastern China.

This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

Human Papillomavirus-Associated Multiphenotypic Carcinoma: First Description of a Vulval Case.

Human papillomavirus (HPV)-associated multiphenotypic sinonasal carcinoma is a rare and recently described epithelial neoplasm exhibiting myoepithelial differentiation and morphological overlap with salivary gland neoplasms, especially adenoid cystic carcinoma; it is commonly associated with HPV, especially type 33. It has mainly been reported in the nasal cavity and paranasal sinuses with a single case reported in the breast. Herein, we report the first vulval example in a 47-year-old patient who presented with a large craggy mass in the region of the Bartholin gland. The histologic features were of a high-grade carcinoma composed of basaloid cells arranged in sheets and nests, with occasional ductal formations, surrounded by densely hyalinised basement membrane-type material. There was diffuse block-type immunoreactivity with p16 and HPV genotyping revealed high-risk HPV type 16. In reporting this case, we highlight the propensity for "salivary gland-type" neoplasms to arise in the vulva, especially in the Bartholin gland, and stress that pathologists should consider salivary-type neoplasms when faced with a morphologically unusual vulval tumor.

Trends in the Prevalence and Mortality of Cervical Cancer in the Kyrgyz Republic.

Cervical cancer represents a significant health concern globally and is the fourth most common cancer among women, leading to substantial morbidity and mortality. The primary cause is persistent infection with high-risk human papillomavirus (HPV) types. Despite advancements in prevention, screening, diagnosis, and treatment, disparities in cervical cancer outcomes persist due to variations in screening accessibility and socioeconomic factors. This study focuses on women in the Kyrgyz Republic, highlighting regional disparities and the critical role of early detection. A retrospective data analysis was conducted on 1,338 women diagnosed with cervical cancer from 2012 to 2017 in the Kyrgyz Republic. Data were sourced from national health centers, focusing on sociodemographic metrics, clinical staging, and regional distributions. The study utilized statistical analysis to evaluate prevalence and mortality rates, employing the analysis of variance for comparison, significance, and analyzing trends over time. The prevalence of cervical cancer in the Kyrgyz Republic increased from 97.5 per 100,000 females in 2012 to 105.3 per 100,000 in 2017, with mortality rates of 8.3-9.7%. Notably, regional disparities were evident, with Chui, Osh, Jalal-Abad, and Bishkek experiencing increased prevalence rates, while Talas, Issyk-Kul, Naryn, and Batken reported decreased prevalence. Screening programs, particularly the introduction of Pap smears, have been effective in reducing both prevalence and mortality rates in areas with broad population coverage. However, the study highlighted significant variations in outcomes across different regions, underscoring the importance of targeted prevention and screening efforts. The study confirms the ongoing challenge of cervical cancer in the Kyrgyz Republic, emphasizing the need for improved screening and prevention strategies to address disparities in outcomes. The introduction of pilot screening programs represents a crucial step forward. However, the findings also point to the necessity for enhanced oncological literacy among primary care physicians and the implementation of comprehensive strategies to overcome socioeconomic and regional barriers to effective cervical cancer prevention and treatment. The reduction in prevalence observed in 2016 suggests progress, highlighting the potential impact of focused prevention and screening initiatives.

Prevalence of Trichomonas Infection in Relation to Human Papillomavirus (HPV) in Pap Smear Samples of Female Patients Referred to Shahid Sadoughi Hospital, Yazd (Iran).

Objectives Human papillomavirus (HPV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for cervical cancer. This study has been conducted with the aim of investigating the prevalence of TV and its relationship with HPV in women who underwent Pap smear testing as part of cancer screenings. Materials and methods The sampling of liquid-based cervical tissue was conducted among 500 women referred to the women's clinic of Shahid Sadoughi Hospital in Yazd, Iran. The studied samples were examined for Pap smear tests and microscopic identification of TV, as well as HPV-DNA detection and the determination of high-risk and low-risk HPV types by the polymerase chain reaction (PCR) method. The results were analyzed using the IBM SPSS Statistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York) software. Results The individuals included in the study were 16-72 years old. The prevalence rate of TV infection in this population was found to be 29.2%, and the frequency rate of HPV was reported to be approximately 19.4%, with high-risk HPV, including HPV-56, having the highest frequency. The Pap smear test results were reported as abnormal in 20.2%, anda significant correlation was observed between HPV infection and an abnormal Pap smear test (P < 0.05). In addition, a notable correlation was detected between TV infection and high-risk and low-risk HPV (P < 0.05). Conclusion According to the significant relationship found between the two pathogens, TV and HPV, in the abnormal Pap smear test results, TV infection can be considered a risk factor for HPV infection, as well as uterine lesions and cancer.

Chlamydia trachomatis and Neisseria gonorrhoeae rectal infections: Interplay between rectal microbiome, HPV infection and Torquetenovirus.

Men having sex with men (MSM) represent a key population, in which sexually transmitted rectal infections (STIs) caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and high-risk HPV (HR-HPV) are very common and linked to significant morbidity. Investigating the anorectal microbiome associated with rectal STIs holds potential for deeper insights into the pathogenesis of these infections and the development of innovative control strategies. In this study, we explored the interplay at the rectal site between C. trachomatis, N. gonorrhoeae, HR-HPV infection, and the anorectal microbiome in a cohort of 92 MSM (47 infected by CT and/or NG vs 45 controls). Moreover, we assessed the presence of Torquetenovirus (TTV), a non-pathogenic endogenous virus, considered as a possible predictor of immune system activation. We found a high prevalence of HR-HPV rectal infections (61%), especially in subjects with a concurrent CT/NG rectal infection (70.2%) and in people living with HIV (84%). In addition, we observed that TTV was more prevalent in subjects with CT/NG rectal infections than in non-infected ones (70.2% vs 46.7%, respectively). The anorectal microbiome of patients infected by CT and/or NG exhibited a reduction in Escherichia, while the presence of TTV was significantly associated with higher levels of Bacteroides. We observed a positive correlation of HR-HPV types with Escherichia and Corynebacterium, and a negative correlation with the Firmicutes phylum, and with Prevotella, Oscillospira, Sutterella. Our findings shed light on some of the dynamics occurring within the rectal environment involving chlamydial/gonococcal infections, HPV, TTV, and the anorectal microbiome. These data could open new perspectives for the control and prevention of STIs in MSM.

Impact of high-performance human papillomavirus testing to improve cervical cancer screening in China: a prospective population-based multicentre cohort study

ObjectivesThe aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. MethodsA total of 9829 eligible women aged 21–64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. ResultsAt baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34–99.31%] vs. 62/80, 77.50% [67.21–85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80–88.12%] vs. 8900/9749, 91.29% [90.72–91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91–96.39%] vs. 87/172, 50.58% [43.18–57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72–89.16%] vs. 6933/7660, 90.51% [89.83–91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old. DiscussionThe study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.

Exploring the Concordance Between High-Risk Human Papillomavirus Infections in Cervical and Oral Sites Among Females: A Cross-Sectional Study in Punjab, Pakistan.

Human papillomavirus (HPV) is widely recognized as a key contributing factor in cervical and oropharyngeal cancers. However, there has been limited research on the prevalence of concurrent HPV infections in various anatomic regions. This study aimed to investigate the prevalence and specific types of high-risk HPV (HR-HPV) infections in the cervical and oral regions of females in Punjab, Pakistan. We conducted a cross-sectional study involving women seeking care for general gynecologic issues at the gynecologic Outpatient Department of Lady Wallington Hospital in Lahore. After interviews and clinical examinations, we collected whole-saliva samples and high vaginal swabs from each participant. HR-HPV detection and genotyping were performed using real-time polymerase chain reaction at both the anatomic sites. In this study, 170 females, averaging 35.36 ± 8.305 years, participated. HR-HPV infection was more prevalent in the cervix (83/170 [48.8%]) than in the oral cavity (19/170 [11.2%]). Concordant HPV infections occurred in 10/170 participants (5.9%). HPV 16 was the most common genotype in cervical and oral locations, at rates of 21.8% and 5.3%, respectively, among concordant HR-HPV types. Socioeconomic status (P = .013), age at first sexual intercourse (P = .015), and history of oral sex (P = .01) were significantly associated with concurrent HR-HPV infection in both regions. This study suggests that HR-HPV cervical infections may increase the risk of oral transmission, especially during orogenital sexual practices. Thus, it is important to recognize that HPV infections may be linked in both areas. We emphasize the importance of comprehensive cervical and oral examinations and HPV vaccination in young women irrespective of their sexual practices.

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.

Clinical Validation of the Vitro HPV Screening Assay for Its Use in Primary Cervical Cancer Screening.

Many scientific societies have issued guidelines to introduce population-based cervical cancer screening with HPV testing. The Vitro HPV Screening assay is a fully automatic multiplex real-time PCR test targeting the L1 GP5+/GP6+ region of HPV genome. The assay detects 14 high risk (HR) HPV genotypes, identifying individual HPV16 and HPV18 genotypes, and the HPV-positive samples for the other 12 HR HPV types are subsequently genotyped with the HPV Direct Flow Chip test. Following international guidelines, the aim of this study was to validate the clinical accuracy of the Vitro HPV Screening test on ThinPrep-collected samples for its use as primary cervical cancer screening, using as comparator the validated cobas® 4800 HPV test. The non-inferiority analysis showed that the clinical sensitivity and specificity of the Vitro HPV Screening assay for a diagnosis of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were not inferior to those of cobas® 4800 HPV (p = 0.0049 and p < 0.001 respectively). The assay has demonstrated a high intra- and inter-laboratory reproducibility, also among the individual genotypes. The Vitro HPV Screening assay is valid for cervical cancer screening and it provides genotyping information on HPV-positive samples without further sample processing in a fully automated workflow.

Current status and challenges in timely detection of cervical cancer in Mexico: expert consensus.

Cervical cancer is a significant public health problem in low- and middle-income countries, accounting for 85% of new cases worldwide. Due to poorly organized screening programs, cervical cancer is more likely to develop in vulnerable groups who do not initiate or rarely undergo screening. Cervical cytology and detecting high-risk human papillomavirus types are the recommended screening tools. Further, these strategies allow for accurately identifying women at a higher risk of cervical cancer and establishing screening times. New detection tools, such as novel biomarkers or automatic HPV detection in the vagina or urine, can improve screening coverage. This review aims to identify the challenges faced by detection programs and screening tools in Mexico to provide evidence-based recommendations to improve early detection programs for cervical cancer.

The distribution of hrHPV genotypes among cervical cancer cases diagnosed across Ghana: a cross-sectional study

BackgroundThe burden of cervical cancer in Ghana is high due to a lack of a national screening and vaccination program. Geographical variations in high-risk Human Papilloma Virus incidence and type should be considered for vaccine improvement and screening in LMICs.MethodsA descriptive, multi-center cross-sectional study with purposive sampling of cases with cervical cancer diagnosed from January 2012 through to December 2018 was employed relying on archived Formalin Fixed Paraffin Embedded (FFPE) tissues from four (4) Teaching Hospitals. Cervical cancers were assessed for histopathological features following WHO guidelines. In addition, the novel Tumour Budding and Nest Size Grade (TBNS) for SCC, SILVA pattern of invasion for EAC and Tumour Infiltrating Lymphocytes (TILs) were assessed. High Risk HPV testing was performed using an isothermal, multiplex nucleic acid amplification method from ATILA biosystem (Mountain View California, USA). The FFPE blocks were tested for 15 hrHPV genotypes. Results were analyzed using SPSS v.26.0, with descriptive statistics and cross-tabulation and chi-square tests done with significance established at p < 0.05.ResultsA total of 297 cases were identified for the study with ages ranging from 20 to 95 years. The peak age group for cervical cancer was 46 to 55 years. For those tested, hrHPV positivity rate was 85.4% [EAC (84.6%) and SCC (85.6%)]. The top five hrHPV serotypes for both histological cancers were 59 (40.0%), 35 (32.0%), 18 (30.0%), 16 (15.0%), and 33 (10.0%) respectively. Approximately, 58.2% of infections were multiple. Single hrHPV infections were mostly caused by hrHPV 59 (28.9%), and 16 (26.3%). TBNS grade for SCC, SILVA pattern of invasion for EAC and TILs did not show any statistically significant relationship with hrHPV.ConclusionWe affirm reported differences in hrHPV types associated with cervical cancer in Ghana with hrHPV types such as 59, 35, and 33 forming a significant proportion of hrHPV types associated with cervical cancer. This difference in hrHPV types should guide vaccine improvement and triaging of hrHPV positives. Though multiple infections are more common, some hrHPV types such as hrHPV 16 and 59 are responsible for most single infections associated with cervical cancer. Simple haematoxylin and eosin-based morphological assessments can improve the prognostication of patients with cervical cancer.

Cervical cancer in Thailand: 2023 update.

Cervical cancer continues to pose a challenge to the health of Thai women, as the second most common cancer after breast cancer. Since high-risk human papillomavirus (HPV) types are the main cause for cervical cancer, cervical cancer screening and HPV vaccination are necessary to reduce the incidence of this disease. At present, the World Health Organization hopes to reduce the incidence of cervical cancer to 4 or less cases per 100,000 women-years using 90%- 70%-90% intervention by 2030. The first intervention involves vaccinating 90% of women aged 15 years with the HPV vaccine. The second intervention involves screening 70% of women between the ages of 35 and 45 years using a high-performance screening test. The third intervention involves detecting cervical lesions in 90% of affected women to enable diagnosis and treatment. In this context, this study reviews trends in the incidence and mortality rates of cervical cancer in Thailand, in addition to providing an up-to-date overview of the causes and necessary risk factors for cervical cancer, as well as reporting on cervical screening and HPV vaccination rates and cervical cancer during the coronavirus disease 2019 (COVID-19) pandemic. This study may prove useful for the formulation of policy aimed at eliminating cervical cancer in Thailand, such as the implementation of a free HPV vaccine service and providing athome kits for cervical screening through clinics and pharmacies. In addition, this review also highlights the need for further research on the effects of the COVID-19 pandemic on cervical cancer screening rates in Thailand.

Abstract 2141: Prevalence of cervical high risk HPV serotypes not covered by the 9vt vaccine in a clinic-based sample of Hispanic women living in Puerto Rico

Abstract Cervical cancer (CC) is the fourth most common female malignancy worldwide. Puerto Rico (PR) has the highest age-adjusted incidence of cervical cancer in the U.S. High-risk strains of human papillomavirus (hr-HPV) have been identified as common causative agents of CC. We aimed to characterize the prevalence of High-Risk HPV (HR-HPV) genotypes among a clinic-based sample of 368 HIV-negative women using a high-resolution approach. We used baseline data from IRB protocol 10510114. Cervical swabs underwent genomic DNA extractions followed by typification of HPV genotypes using a short-polymerase chain reaction-fragment assay (SPF10-LiPA) which detects 14 mucosal HR-HPV types (LiPA-25); 10 types (8 HR and 2LR) included in the 9-valent vaccine and 13 others not included on it. This process uses SPF10 primers to amplify a 65 bp fragment of the L1 open reading frame of HPV, followed by a reverse-hybridizationfor specific HPV genotypes by comparing the results to standardized kit controls. Cervical cytology was acquired for all participants. Data was collected from 186 women negative to intraepithelial lesions (NILM), 65 with low-grade lesions (LGSIL), 23 atypical squamous cells of undetermined significance (ASCUS) and 94 with high-grade lesions (HGSIL).Among study results, the prevalence of any HR-HPV infection was high overall (~71.5%) and higher in women who had either LGSIL or HGSIL. The top leading HR types detected were 51 (20.4%), 16 (18.5%), 52 (13.60%), 33 (13.00%) and 56 (11.00%, with other types including HPVs 35,39, 68 or 59.Nearly 34.00% of the identified cervical HR-HPV types, are not included in the 9-valent vaccine. The most common HPV types in HGSIL, included HR HPV types 16 (30.9%), 52 (18.10%), 51 (14.9%) and 33 (10.60%). In this group, only 35.20% were HPV16/18. The other 64.80% were other HR-HPV types and, based on the ASCCP guidelines, would not require a colposcopy, and could be observed in one year. Among these HGSIL (n=94) 48.9% of the HPV types were not included in the vaccine. HPV 51 was the most dominant in ASCUS (26.10%), LGSIL (20%), and women who were negative for intraepithelial lesions (NILM 22.6%). Additionally, the most prevalent HPV-HR serotypes across all cytology categories in the vaccinated cohort were 52 (11.14%), 16 (8.02%) and 31 (7.56%), whereas in the non-vaccinated cohort were HPV 16 (20.6%), 51 (17.55%), 33 (13.33%), 52 (12.29%), and 56 (11.94%).In conclusion, the high burden of other high-risk types not covered by the vaccine in women with high-grade lesions suggests that delaying immediate colposcopy might limit the identification of cervical lesions. Even though this is not a population-based study, the high prevalence of these other HR-HPV types calls for their inclusion in future generations of the vaccine. Study sponsored by 2U54MD007600-36 (8538) Research Centers in Minority Institutions of the University of Puerto Rico (NIH/NIMHD). Citation Format: Romaguera Josefina, Bianka Morales, Andrea Cortes, Ana Rosario, Andrea Padilla-Bou, Maria Frontera, Claudia Rosado, Daniela Cargas-Robles, Ana P. Ortiz, Filipa Godoy-Vitorino. Prevalence of cervical high risk HPV serotypes not covered by the 9vt vaccine in a clinic-based sample of Hispanic women living in Puerto Rico [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 2141.

Abstract 3948: HPV45 and HPV52 prevalence, within-type variants, and precancer/cancer risks differ by race/ethnicity

Abstract Introduction: Persistent infection with a high-risk HPV (HR-HPV) type causes cervical cancer and many other cancers in both men and women. Our published data have shown that the distribution of specific HPV16/35 sublineages and genetic variants differ around the world and confer greater risk of cervical precancer/cancer in the populations where the virus is thought to have originated and coevolved. More studies are needed to evaluate the relationship between race/ethnicity, HR-HPV genetic variation, and precancer/cancer risk. Objective: To evaluate HPV45 and HPV52 genetic variation, and how it relates to a woman’s race/ethnicity and cervical precancer/cancer risk, using HPV whole-genome sequencing of 774 HPV45+ and 719 HPV52+ women in the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression cohort; and compared to HPV16/35. Methods: We viral genome sequenced 557 HPV45+ and 345 HPV52+ controls (women with benign infections [≤CIN1]), and 94 HPV45+ and 227 HPV52+ precancer/cancer cases (CIN3+). We evaluated HPV45 and HPV52 prevalence for each type by a woman’s self-reported race/ethnicity, and compared them to HPV16 and HPV35 using existing comparable NCI-KPNC data. To assess associations between HPV45 and HPV52 genetic variation (viral sublineages and SNPs) and infection outcome, we used Fisher’s Exact Tests and logistic regression to estimate the OR and 95% CI. Results: For HPV45, we determined that sublineages have varying histology-specific precancer/cancer risk (ORs ranged from 2-14), and that the sublineage distribution significantly varied by race/ethnicity (p &amp;lt; 0.001). By race, the HPV45 A2 sublineage was most prevalent in Asian/PI women and was associated with the highest risk of CIN3+ in these women compared to other races/ethnicities (OR=5.7, 95% CI=1.5-29.4), while the B2 sublineage was associated with increased risk of CIN3+ in Black women only (OR=6.1, 95% CI=1.2-33.6). The prevalence of each HR-HPV type (HPV16/35/45/52) significantly varied by race/ethnicity (p &amp;lt; 0.001). For each type, White was the most reported race/ethnicity; however, Black women were a greater proportion of the HPV35+ cases compared to other types (15% vs 8-10%), and Asian/PIs were a greater proportion of HPV52+ cases (26% vs 10-13%). HPV52 genome analyses are still underway; we will present the complete study results (i.e., sublineage risk by race) at AACR. Conclusions: We conducted the largest studies of HPV45 and HPV52 genome variation to date. We demonstrate that specific HPV45 sublineages vary by race and are associated with an increased risk of precancer/cancer for specific races/ethnicities, and that HPV52 infection has a greater prevalence in Asian/PI women compared to other racial groups. Our data suggest that certain HR-HPV types and specific sublineages of these types are more common in specific racial/ethnic groups and potentially linked to differing risks by race. Citation Format: Aimee J. Koestler, Chase W. Nelson, Meredith Yeager, Zigui Chen, Laurie Burdett, Sambit K. Mishra, Michael Dean, Elizabeth Suh-Burgmann, Thomas Lorey, Phillip E. Castle, Mark Schiffman, Lisa Mirabello. HPV45 and HPV52 prevalence, within-type variants, and precancer/cancer risks differ by race/ethnicity [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 3948.

Abstract 4804: Prevalence of anal HPV infection in women attending a gynecology and colposcopy clinic: Assessing the potential impact of HPV vaccination

Abstract Human papillomavirus (HPV) accounts for over 80% of anal cancer cases. In the effort to prevent HPV-related cancers, the 9-valent HPV vaccine emerged as a crucial intervention, targeting HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; the previous 4-valent (types 6,11,16,18) and 2-valent (types 16, 18). This study involved 213 women aged 21-50 attending gynecology and colonoscopy clinics in San Juan, Puerto Rico. The study assessed anal HPV prevalence and analyzed vaccination status-related differences. Anal swabs were collected for HPV testing using the ATILA AmpFire, targeting 17 HPV types. This method identified 15 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68) and two low-risk HPV types (6 and 11). Prevalence of any HPV, HR-HPV, and LR-HPV, and of specific HPV types were calculated by overall and vaccination status. Differences were assessed for statistical significance (p&amp;lt;0.05) using Fisher's exact or Pearson χ2 test. The mean age of women was 36.0 ± 5.9 years. Overall, 19.7% (n=44) had received the HPV vaccine; among them, 52.2% (n=23) had received the 4-valent vaccine, 2.3% had received the 2-valent vaccine, 2.3% had received the 9-valent vaccine, and 43.2% were uncertain about their specific HPV vaccine type. The prevalence of anal HPV infection was 68.5% for any HPV, 61.5% for HR-HPV, and 15.0% for LR-HPV. The most prevalent HR-HPV types were HPV 56 (13.2%), HPV 68 (11.7%), and HPV 66 (11.2%). There were no statistically significant differences in the prevalence of any HPV, HR-HPV, and LR-HPV between vaccinated and unvaccinated women. The most common HR-HPV type among vaccinated were HPV 66 (20.5%), HPV 31 (18.2%), HPV 56 (15.9%), while the most common among unvaccinated women were HPV 56 (12.4%), HPV 68 (12.4%), and HPV 16 (12.4%). Additionally, when evaluating as a grouped variable, the HPV genotypes covered by the 4-valent, unvaccinated women had a significantly higher prevalence of these types as compared to those vaccinated (28.9% vs. 13.6%, respectively, p-value =.03). The unvaccinated women showed a lower prevalence for HPV types covered by the 9-valent vaccine compared to the vaccinated cohort (43.2% vs. 45.5%). However, this difference was not statistically significant. We found a high prevalence of anal HPV among these women, with lower prevalence of 4-valent and 2-valent HPV types among vaccinated women, evidencing the pivotal role of HPV vaccination. Future research should assess the 9-valent vaccine's long-term effectiveness against more HPV types. Funding: Research Centers in Minority Institutions (RCMI), University of Puerto Rico (NIMHD # 2U54MD007600-36), and CAPAC Research Training Program (NCI #R25CA240120). Citation Format: Anelisse Dominicci-Maura, Ana Patricia Ortiz, Josefina Romaguera, Filipa Godoy-Vitorino. Prevalence of anal HPV infection in women attending a gynecology and colposcopy clinic: Assessing the potential impact of HPV vaccination [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 4804.

CLIA Validation of a New High Performance HPV ctDNA Assay Covering Multiple High Risk HPV Types

CLIA Validation of a New High Performance HPV ctDNA Assay Covering Multiple High Risk HPV Types

Prevalence of Human Papillomavirus (HPV) and HPV Type Distribution in Penile Samples in Young Men in Denmark: Results 10 Years After Implementation of a Girls-Only HPV Vaccination Program.

In Denmark, a girls-only human papillomavirus (HPV) vaccination program was initiated in 2008-2009. The study aim was to assess the HPV prevalence and type distribution in younger men prior to HPV vaccination in men. The study population was younger men who attended information days regarding military service. At random days (2019-2020), 280 men were included. We collected questionnaire data regarding risk factors for HPV infection and a penile swab for HPV testing. We compared results in this study with those from a previous study of young men (2006-2007). The majority of participants (94%) were 18-20 years old. The median number of lifetime sexual partners was 4. Altogether, 130 men (46.4%) were HPV positive. No infections with HPV types 6, 11, 16, 18, 31, and 45 were detected. The most frequent type was HPV-51 (detected in 11.1%). Comparison showed that the odds of high-risk HPV type infection were higher in 2019-2020 (prevalence odds ratio [POR], 1.7 [95% confidence interval {CI}, 1.1-2.7]) compared with 2006-2007. In contrast, the odds were lower (POR, 0.3 [95% CI, .1-.6]) for HPV types targeted by the 9-valent HPV vaccine. The multicohort girls-only vaccination program has to a large degree protected young men against the HPV types included in the licensed vaccines. This does not speak against gender-neutral vaccination as the HPV prevalence is still high, although consisting largely of less carcinogenic HPV types.

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.

Prevalence and Correlation between High-Risk HPV Genotypes and Pap Smear Findings in Bahrain: A Retrospective Approach

Background: Human papillomavirus (HPV) is currently the most common pathogen responsible for cervical cancer (CC), a major cause of cancer-related deaths in women. This study aimed to estimate the current HPV prevalence in Bahrain and to determine the association of high-risk HPV (HR-HPV) genotypes with cytological findings, age, and clinical history of the patients. Methods and Results: Our study used a retrospective approach. Convenience sampling was used to gather 100 cases of HPV-positive women with abnormal and normal Pap smear findings from January 2017 to April 2023 in the Cytology Department at King Hamad University Hospital. Out of 100 HR-HPV positive cases, non-16/18/45 HR-HPV was found in 62%, and 73% had abnormal Pap smear findings. Among Pap smear findings, ASC-US/ASC-H (P=0.038) and LSIL/HSIL(P=0.017) were significantly associated with HR-HPV genotypes.ASC-US was found to be more frequently associated with HPV16+non-16/18/45 HR-HRV and LSIL with HPV18/45+non-16/18/45 HR-HRV. Most HR-HPV cases (59%) were aged ≤40 years, 25% - from 41 to 50 years old, while only 16% were &gt;50. The age group ≤40 had the highest peak with non-16/18/45 HR-HPV genotype (35%) and HPV16 (19%). The predominant genotypes for age groups 41-50 and &gt;50 were non-16/18/45 HR-HPV types (19% and 8%, respectively). Conclusion: In Bahrain, non-16/18/45 HR-HPV infection is becoming more prevalent, with ASC-US being the most common abnormal Pap finding and the highest HPV infection in women aged 40 years or younger.Based on our findings, we recommend effective screening and vaccine programs for women aged 40 years and younger, as early detection can lower infection rates and improve recovery.

Correlation between high-risk HPV infection and p16/Ki-67 abnormalities in Pap samples in a South Eastern Europe cohort.

Cervical cancer (CC) is the fourth most common cause of cancer-related deaths amongst women worldwide. CC represents a major global healthcare issue, and Romania ranks the worst in mortality rates amongst EU countries. However, the early detection of CC can be lifesaving. To understand the testing process undergone by women in Romania, we performed a retrospective study, and investigated a cohort of 83 785 cervical cases from Romanian women aged 15-70, obtained in private-based opportunistic screening. We examined the correlation between Pap smear results, human papilloma virus (HPV) genotyping, and the expression of cell cycle markers p16 and Ki-67. Analysis of Pap results revealed approximately 10% abnormal cases, of which high-grade squamous intraepithelial lesionsconstituted 4.9%. HPV genotyping of 12 185 cases with available Pap results unveiled a range of high-risk HPV (hrHPV) types associated with cervical abnormalities. Notably, 26% of hrHPV-positive cases showed no observable abnormalities. In a subset of cases with abnormal Pap and a type of hrHPV, P16/Ki-67 double-staining was also positive. This study suggests the importance of an integrated diagnostic algorithm that should consider the HPV genotype, Pap smear, and p16/Ki-67 staining. This algorithm should enhance the CC screening accuracy and its management strategies, particularly in those regions with a high disease burden, such as Romania.