Cervical High-risk Human Papillomavirus Research Articles

Trends in high-risk human papillomavirus infection and cervical cytology of women in Karamay City, 2012-2021.

Background To describe the changes in cervical lesions prevalence and high-risk human papillomavirus (HR-HPV) infections from 2012 to 2021, which have never been reported before, to provide direction for the effective implementation of cervical cancer prevention measures. Methods This retrospective study included women aged >25years who received either organised or opportunistic cervical HR-HPV screening from January 2012 to December 2021 in Karamay Central Hospital, Karamay, China. The patients were split into four groups according to age 25-35, 36-45, 46-55 and >55years, respectively. The Joinpoint Regression Program was used to analyse the trends of HR-HPV infection and the detection of cervical lesions. Results Data from 85,429 women revealed a decline in HR-HPV infection rates across all age groups from 2012 to 2021. Although HR-HPV infection rates decreased, cervical lesion detection rates increased, although the proportion of cervical cancer in these lesions declined, likely due to enhanced awareness and HPV vaccination in Karamay. From 2012 to 2021, the prevalence of low-grade squamous intraepithelial lesions was 9.70%, and high-grade squamous intraepithelial lesions was 5.85%. HR-HPV infections were highest in the ≥55years age group, with HPV52 (20.96%) being the most prevalent type. Conclusions In the past 10years, the prevalence of HR-HPV infection has shown a decreasing trend, whereas the detection prevalence of cervical lesions has shown an upward trend among women in Karamay City. Importantly, particular emphasis should be placed on cervical cancer screening in women aged >55years.

Concomitant Cervical and Anal Screening for Human Papilloma Virus (HPV): Worth the Effort or a Waste of Time?

This study represents a follow-up analysis of the AnusGynecology (ANGY) study. This prospective, cross-sectional, single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. 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, representing the study cohort for this follow-up study. Overall, 275 patients (mean age 42 ± 12) were included. Among them, 102 (37%) had cervical high-risk (HR) HPV. In total, HPV was (incidentally) revealed in 91 patients (33%) on anal smears, while any degree of anal squamous intraepithelial lesion (SIL) was found in 30 patients (11%), 6 if which were high-grade SIL (H-SIL). Furthermore, 10 out of 19 biopsies were positive (3 H-SIL lesions). Only half (48/91, 53%) of the women agreed to undergo the recommended specialized follow-up evaluation. Of them, 18 (38%) were diagnosed with dysplastic lesions (9 low grade (L-SIL) and 9 H-SIL, respectively) on biopsies, while the remaining visits revealed no abnormalities. Multivariable analysis revealed cervical HR-HPV infection (OR 4, 95% CI 2.2-7.5) and anal intercourse (OR 3.1, 95% CI 1.7-5.9) as independent risk factors for anal HR-HPV infection. Close follow-up of these women is hence strongly recommended.

A comparative study of self-collected versus clinician-collected specimens in detecting high-risk HPV infection: a prospective cross-sectional study.

The primary objective of this study was to compare the detection rate of high-risk human papillomavirus (HPV) infection between self-sampling to collect vaginal specimens and clinician sampling to collect cervical specimens, as well as the correlation between the two techniques. The secondary objective was to assess satisfaction with self-sampling for HPV testing. From October 2021 to September 2022, women positive for HPV 16/18 and other 12 high-risk HPV genotypes and cytological ASCUS were enrolled. All participants were instructed on the method for self-collection of HPV samples. Self-collected vaginal samples and clinician-collected cervical samples were subjected to HPV DNA typing. Paired self- and clinician-collected specimens were obtained from 104 women with positive HPV-positive results. The detection rate of high-risk HPV infection was comparable between the two techniques: 79/98 (80.6%) vs. 81/98 (82.7%) for the self-sampling and clinician-sampling techniques, respectively (McNemar's test; P=0.774). The agreement in detecting HPV infection was substantial, with a kappa coefficient of 0.75. More than 90% of the participants rated self-collection as satisfactory to very satisfactory because of its convenience and safety. Regarding methods of further follow-up, 51% of the participants chose self-sampling, whereas the remaining participants preferred collection by clinicians. No intervention-related complications were observed. The self-sampling technique for HPV testing was as effective as the clinician-sampling technique, and both techniques were substantially correlated in detecting high-risk HPV infection. The self-sampling method appears to be highly satisfactory and may provide better compliance for the detection of cervical HPV infection.

Co-infection of human papillomavirus and herpes simplex virus-2 with cervical dysplasia among women in Kaduna State, Nigeria

Background: The epidemiology of human papillomavirus (HPV) and co-infections with herpes simplex virus type 2 (HSV-2) remains poorly characterized in Africa. High risk HPV (hrHPV) infection is the primary cause of 99.7% all cervical cancer especially in the presence of genital ulcer disease (GUD) which is usually caused by HSV-2. Herpes simplex virus-2 might interact directly with hrHPV to increase the risk of cervical cancer. Co-infection of HPV and HSV-2 in asymptomatic women could provide a clue to early diagnosis of cervical cancer and this could aid in the development of new strategies for effective management and improvement of the quality of life of women who are infected. If the synergy between HPV and HSV-2 can be prevented, there may be significant reduction of the incidence of cervical cancer. Methodology: This was a descriptive cross-sectional study of 515 randomly selected apparently healthy women of reproductive age whose cervical samples were screened for HPV and HSV-2 in Kaduna State, Nigeria. The cervical samples were collected by liquid-based cytology (LBC) for detection of cervical epithelial cell abnormalities (CEA) and molecular detection of HPV and HSV-2 using conventional polymerase chain reaction (PCR) assay. Extracted viral DNAs from the samples were amplified by convectional PCR using specific hrHPV (HPV 16,18, 31 and 45) primer sets and a broad spectrum MY09/11 and GP5+/6+ primers for a wider range of HPV genotypes while HSV-2 DNA was detected by florescence-based PCR assay with HSV-2 gG primers and probes. Results: PCR assay revealed that 14.7% (n=76) of the 515 selected women harbored HPV, HSV-2 or both. The prevalence of HPV, hrHPV, HSV-2 and HPV/HSV-2 co-infection among in the study participants are 11.8% (n=61), 9.3% (n=48), 5.6% 4% (n=29) and 2.3% (n=12) respectively. The frequency of HPV detection in HSV-2 infected participants (41.4%, 12/29) was significantly higher (OR=6.295, p<0.0001) than in HSV-2 negative participants (10.1%, 49/437), but only co-infections of HPV-31 (p=0.004) and HPV-18 (p=0.040) with HSV-2 were significantly associated. Cervical cytology reports on the smears revealed prevalence of cervical epithelial abnormalities (CEA) of 16.7% (n=86), with cervical dysplasia prevalence of 6.4% (n=33), consisting of high grade squamous intraepithelial lesion (HGSIL) of 1.6% (n=8), low grade squamous intraepithelial lesion (LGSIL) of 4.1% (n=21) and atypical squamous cells of uncertain significance (ASCUS) of 0.8% (n=4). The frequency of HPV detection in women with cervical dysplasia (93.9%, 31/33) was significantly higher (OR=14.22, p<0.0001) than in women without cervical dysplasia (6.2%, 30/482), and all HPV genotypes were significantly associated (p<0.05) with cervical dysplasia except HPV 16 (p=0.051). Also, the frequency of HPV/HSV-2 co-infection among women with cervical dysplasia (15.2%, 5/33) was significantly higher than among women without cervical dysplasia (1.5%, 7/482) (OR=12.12, p<0.0001). Comparing women with cervical inflammatory and atrophic changes (n=53), women with cervical dysplasia (HGSIL, LGSIL and ASC-US) had significantly higher frequency of HPV infection (χ2=42.829, p=0.000), HSV-2 infection (χ2=25.140, p=0.001) and HPV/HSV-2 co-infections (χ2=66.602, p=0.000). Conclusion: Co-infection rate of hrHPV and HSV-2 among women in Kaduna State is 2.3%. Demographic factors significantly influencing the rate of co-infections included age and marital status. In spite of the screening method using the traditional Pap smear, GUD and cervical cancer continues to be a major public health problem, thus more sensitive and specific methods such as liquid based cytology technique and polymerase chain reaction for early detection of cervical dysplasia and hrHPV or HSV-2 in asymptomatic women should be adopted for routine use

Cross-Sectional Study on the Correlation Between Vaginal Microecology and High-Risk Human Papillomavirus Infection: Establishment of a Clinical Prediction Model.

High-risk human papillomavirus (HR-HPV) is a significant risk factor for cervical precancerous lesions and cancer. This study aimed to investigate the relationship between vaginal microecology and HR-HPV infection and to evaluate the clinical applicability of vaginal microecology in predicting HR-HPV infection. Overall, 2000 women with simultaneously detected vaginal discharge and cervical HPV were selected between March 2022 and March 2023, including 241 and 1759 cases in the HR-HPV positive and HPV negative groups, respectively. No significant differences were found in age, vulvovaginal candidiasis, trichomonas vaginitis, and β-N-acetylglucosaminosidase between the two groups (P>0.05). Significant differences were observed in Lactobacillus deficiency, bacterial vaginitis (BV), aerobic vaginitis (AV), glucuronidase (GUS), sialidase (SNA), and leukocyte esterase (LE) between the two groups (P<0.05). In the multivariate logistic regression equation, Lactobacillus deficiency, BV, AV, SNA, LE, and GUS were risk factors for HR-HPV infection (P<0.05). Three prediction models, namely, logistic regression, decision tree, and random forest, were established to rank the importance of the predictors. BV ranked first among the three prediction models. The logistic regression model demonstrated the highest accuracy in predicting the risk of HR-HPV infection. The calibration curve of the logistic regression model showed a strong correlation between the predicted and actual probabilities, and decision curve analysis revealed that the prediction model had good clinical applicability. Overall, vaginal microecology imbalance was closely associated with cervical HR-HPV infection, particularly BV and AV. The logistic regression model for the risk of HR-HPV infection based on six predictive factors (BV, AV, LE, SNA, Lactobacillus deficiency, and GUS) had good accuracy and clinical applicability.

Prevalence of 14 high-risk human papillomavirus subtypes among volunteers of cervical cancer screening by Papanicolaou smear cytology from a tertiary care institute of Assam, India

Abstract: BACKGROUND: In India, cervical cancer is the second most prevalent cancer among women, constituting 18.3% of all cases. Persistent high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer. OBJECTIVES: This study aimed to assess the prevalence of 14 high-risk HPV subtypes and their association with abnormal cytology among women in Upper Assam. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted from February 2022 to April 2023 at a tertiary care center in Assam. A total of 100 women aged 23-72 years underwent cervical sample collection for HPV DNA analysis via real-time polymerase chain reaction and cytological examination of Papanicolaou (PAP) smears. RESULTS: The overall HPV prevalence was 13%, with 10% testing positive for HPV 16/18 and 6% for other high-risk subtypes. Coinfection with HPV 16/18 and other subtypes was found in 3% of cases. The mean age of HPV-positive participants was 46 years. Cytology results showed 87% normal, 11% inflammatory changes, and 2% epithelial cell abnormalities. The Chi-square analysis (α = 0.05) showed no significant association between age (P = 0.24), religion (P = 0.49), or education (P = 0.57) and HPV positivity, but the study showed a significant association of HPV infection with menstrual cycle (P = 0.04). The study also showed a significant association between cervical cytology and HPV positivity (P = 0.0087). DISCUSSION: The present study’s findings on the prevalence of all 14 high-risk HPV subtypes contribute new insights to the existing literature, although the slightly lower prevalence may be attributed to the sample size and demographic factors. The findings emphasize the need for regular screening by PAP smear as well as by HPV DNA detection, as cytological abnormalities were detected even in those without HPV infection. CONCLUSION: Along with 16/18 HPV subtypes, a longitudinal study may offer important insights into the development of coinfections and the other 12 subtypes of HPV infection, as well as the spectrum of dysplasia and in situ cervical cancer.

Human Papillomavirus Genotypes Distribution in High-Grade Cervical Lesions and Invasive Cervical Carcinoma in Women Living in Mauritania: Implications for Cervical Cancer Prevention and HPV Prophylactic Vaccination.

Cervical cancer related to high-risk human papillomavirus (HR-HPV) is the second female cancer in Mauritania (Northwest Sahelian Africa). We assessed the distribution of HPV genotypes in Mauritanian women with high-grade cervical intraepithelial neoplasia (CIN2/3) or invasive cervical cancer (ICC). A prospective study was conducted in the Centre Hospitalier National, Nouakchott, Mauritania, to collect cervical biopsies among women suspected of CIN2/3 or cancer. HPV DNA detection and genotyping were carried out from formalin-fixed, paraffin-embedded biopsies using multiplex PCR (Human Papillomavirus Genotyping Real-Time PCR Kit, Bioperfectus Technologies Co., Taizhou, China). Fifty biopsies were included from women (mean age: 56.7 years) suffering from CIN2/3 (28.0%) and ICC (72.0%) which corresponded to 32 (64.0%) squamous cell carcinomas (SCC) and 4 (8.0%) adenocarcinomas (ADC). HPV DNA detection was successful in 47 (94.0%) samples. The most prevalent HR-HPV genotypes were HPV-45 (40.4%), HPV-16 (38.3%), HPV-39 and HPV-52 (23.4%), HPV-33 (17.0%), HPV-18 (14.9%), HPV-35 (4.2%), and HPV-56 (2.1%). The majority (93.6%) of HPV-positive biopsies contained at least one HPV type covered by the 9-valent Gardasil-9® vaccine, and 40.9% were infected by multiple vaccine HPV genotypes. To eradicate cervical cancer in Mauritania, prophylactic HPV vaccination must be combined with primary molecular screening of cervical HR-HPV infection.

Decoding Cervical High Risk HPV Genotype Disparities: A Comprehensive Study on Racially, Ethnically, and Gender Diverse Populations

Decoding Cervical High Risk HPV Genotype Disparities: A Comprehensive Study on Racially, Ethnically, and Gender Diverse Populations

High-risk human papillomavirus infection and cervical cytopathology: relationship with cervical nitric oxide levels

BackgroundNitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia.MethodsThe study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction.ResultsHigh-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5–45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2–9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6–94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6–33.3 and 34.5 µmol/mL, IQR: 11.7–61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively.ConclusionsThe high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.

Safety and Immunogenicity of the Nonavalent Human Papillomavirus Vaccine in Women Living with HIV.

The objectives were to evaluate the safety and immunogenicity of the nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in the anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa. In this single-center, open-arm, non-randomized clinical trial, the nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and/or colposcopy. A total of 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% were infected by HR-HPV in the anus and 25.4% in the cervix, most frequently HPV 16; 19.1% had anal intraepithelial neoplasia 1-(AIN1); and 3.1% had cervical intraepithelial neoplasia 1 and 2 (CIN1/CIN2). Vaccine administration did not modify viral-immunological status (CD4 [809 ± 226.8 cells/uL vs. 792.35 ± 349.95; p = 0.357]) or plasma HIV load (3.38 ± 4.41 vs. 1.62 ± 2.55 cop/uL [log]; p = 0.125). Anti-HPV antibodies ([IQR: 0-0] vs. 7.63 nm [IQR: 3.46-19.7]; p = 0.0001) and seroconversion rate (8.2% vs. 96.7% [p = 0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of the participants. HR-HPV infection in the anus was solely associated with a concomitant cervix infection (HR 5.027; 95% CI: 1.009-25.042). nHPV vaccine in adult WLHIV is immunogenic and safe.

Exploring the mechanisms of Qingdu Fang for the treatment of cervical HR-HPV using UPLC-QTOF-MS, network pharmacology, and cell experimentation.

Background: Qingdu Fang (QDF) is a traditional Chinese herbal formula with remarkable clinical effect in the treatment of HR-HPV, but its mechanism remains unclear. In this study, UPLC-QTOF-MS was used to detect its components, network pharmacology was used to explore the traditional Chinese medicine monomers and their related targets for the treatment of HR-HPV in QDF. Molecular docking and in vitro experiments were performed to verify the results. Methods: QDF constituents and active compounds were identified using UPLC-QTOF-MS analysis. TCMSP and GeneCard databases were used to identify active components, targets, and potential therapeutic targets in HR-HPV. PPI network was constructed using the String database to analyze protein-protein interactions. Cytoscape3.7.2 was used to construct PPI networks, while GO enrichment and KEGG pathway analyses with R. The effect of QDF on H8 cell proliferation was measured using the CCK-8 method, and apoptosis and cell cycle was assessed with flow cytometry. The effects of QDF on PI3K/AKT pathway were detected by Western blotting. Results: A total of 27 compounds were identified on QDF by UPLC-QTOF-MS. Base on Network pharmacology,a total of 254 target genes are involved in the action of QDF on cervical HR-HPV. PPI analysis suggested that TP53, JUN, AKT1, STAT3, TNF and IL6 were potential targets for QDF treatment of HR-HPV. Molecular docking shows that two compounds have strong binding activity with AKT1. CCK-8 and morphological observation have shown that QDF inhibits H8 cell proliferation in a dose-dependent manner. Flow cytometry experiments suggest that QDF induces apoptosis and cell cycle arrest in H8 cells. Western blotting experiments reveal that QDF inhibits the PI3K/AKT signaling pathway. Conclusion: QDF has a multi-faceted therapeutic approach for HR-HPV, targeting inflammation, oxidation, and apoptosis. It induces apoptosis in H8 cells by inhibiting the PI3K/AKT pathway.

The association between smoking and cervical human papillomavirus infection among women from indigenous communities in western Botswana

Introduction Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. Methods A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. Results A total of 171 participants with a median (interquartile range) age of 40 (31–50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. Conclusion These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.

The efficacy and safety of local 5-aminolevulinic acid-based photodynamic therapy in the treatment of cervical high-grade squamous intraepithelial lesion: a single center retrospective observational study.

Typical treatments for cervical high-grade squamous intraepithelial lesion (HSIL) are invasive procedures. However, these procedures often come with several severe side effects, despite their positive effects on cervical HSIL. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive treatment that has been successfully used to treat cervical low-grade squamous intraepithelial lesion (LSIL). In this study, we aimed to further investigate the clinical efficacy and safety of ALA-PDT in the treatment of patients with cervical HSIL. A total of 40 patients aged 20 - 41 years with cervical HSIL and high-risk Human Papilloma Virus (HR-HPV) infections were enrolled in this retrospective study from January 2019 to December 2022. Patients were treated with six times of ALA-PDT at intervals of 7-14 days. Three months after the treatment, the efficacy was evaluated through HPV genotyping and cervical cytology examination. If the cytological result was worse than ASC -US, the patient underwent colposcopy-directed biopsy immediately. Otherwise, patients would receive rigorous follow-up observation. Three months after receiving ALA-PDT treatment, 65% (26/40) of cervical HSIL patients at our center showed complete regression (cytological result: normal; HR-HPV: negative). This rate increased to 82.5% (33/40) at the 12-month follow-up. None of the patients experienced disease progression after ALA-PDT therapy. The risk of persistent HR-HPV infection was 32.5% (13/40) at the 3-month follow-up after ALA-PDT. Multivariate analyses identified cervical canal involvement as an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment. During the treatment of the 40 patients with ALA-PDT, there were no reports of severe adverse reactions. Only a limited number of patients experienced slight discomfort symptoms. ALA-PDT is safe and effective noninvasive therapy for patients with cervical HSIL and HR-HPV infections. It is particularly suitable for young women, who have been confirmed with cervical HSIL and have demand for fertility protection. Three months after ALA-PDT treatment, if a patient still has either ASC-US cervical cytological result and/or HR-HPV infection, rigorous observation is considered safe for her. Cervical canal involvement is an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment.

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

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

Incidence and clearance of cervical and anal high-risk human papillomavirus in kidney transplant recipients: Results from a Danish prospective clinical study

This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening.

Analogies between HPV Behavior in Oral and Vaginal Cavity: Narrative Review on the Current Evidence in the Literature.

Human genital papilloma virus infection is the most prevalent sexually transmitted infection in the world. It is estimated that more than 75% of sexually active women contract this infection in their lifetime. In 80% of young women, there is the clearance of the virus within 18-24 months. In developed countries, oral squamous cell carcinoma (OSCC) is now the most frequent human papilloma virus (HPV)-related cancer, having surpassed cervical cancer, and it is predicted that by 2030 most squamous cell carcinomas will be the HPV-related rather than non-HPV-related form. However, there are currently no screening programs for oral cavity infection. While the natural history of HPV infection in the cervix is well known, in the oropharynx, it is not entirely clear. Furthermore, the prevalence of HPV in the oropharynx is unknown. Published studies have found wide-ranging prevalence estimates of 2.6% to 50%. There are also conflicting results regarding the percentage of women presenting the same type of HPV at two mucosal sites, ranging from 0 to 60%. Additionally, the question arises as to whether oral infection can develop from genital HPV infection, through oral and genital contact or by self-inoculation, or whether it should be considered an independent event. However, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. Therefore, this literature review aims to evaluate whether there is evidence of a connection between oral and cervical HPV, while also endorsing the usefulness of the screening of oral infection in patients with high-risk cervical HPV as a means of facilitating the diagnosis and early management of HPV-related oral lesions. Finally, this review emphasizes the recommendation for the use of the HPV vaccines in primary prevention in the male and female population as the most effective means of successfully counteracting the increasing incidence of OSCC to date.

Exploring the Mechanisms of Action of Quercetin for the Treatment of Cervical High-Risk-Human Papilloma Virus Using Network Pharmacology and Molecular Docking

Abstract Objective Our objective was to investigate the therapeutic mechanism of quercetin in the management of cervical HR-HPV through the integration of network pharmacology and molecular docking techniques. Methods The GeneCard database was utilized to analyze and identify potential therapeutic targets in HR-HPV. Subsequently, a protein–protein interaction (PPI) network was constructed by employing the String database. The visualization and construction of PPI networks were accomplished using Cytoscape. The R language was utilized to conduct Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results A total of 154 active constituents of quercetin were identified through screening. Additionally, 139 target genes associated with the effects of quercetin on cervical HR-HPV were predicted. PPI analyses revealed that threonine kinase Akt1, mitogen-activated protein kinase1, human IL-6 protein, signal transducer and activator of transcription 3, and epidermal growth factor receptor (EGFR) may serve as potential targets for quercetin in the treatment of cervical HR-HPV. Furthermore, GO and KEGG analyses demonstrated that quercetin is involved in various functional pathways, biological processes, molecular categories, including the Th17 signaling pathway, tumor necrotizing factor (TNF) signaling pathway, EGFR signaling pathway, PI3K-Akt signaling pathway, among others. Conclusion Quercetin exhibits multifaceted characteristics, targeting multiple components, pathways, and targets, in the therapeutic intervention of HR-HPV, primarily by modulating inflammatory responses, oxidation reactions, and apoptotic processes.

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

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

Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections

Genetic variants that underlie susceptibility to cervical high-risk human papillomavirus (hrHPV) infections are largely unknown. We conducted discovery genome-wide association studies (GWAS), replication, meta-analysis and colocalization, generated polygenic risk scores (PRS) and examined the association of classical HLA alleles and cervical hrHPV infections in a cohort of over 10,000 women. We identified genome-wide significant variants for prevalent hrHPV around LDB2 and for persistent hrHPV near TPTE2, SMAD2, and CDH12, which code for proteins that are significantly expressed in the human endocervix. Genetic variants associated with persistent hrHPV are in genes enriched for the antigen processing and presentation gene set. HLA-DRB1*13:02, HLA-DQB1*05:02 and HLA-DRB1*03:01 were associated with increased risk, and HLA-DRB1*15:03 was associated with decreased risk of persistent hrHPV. The analyses of peptide binding predictions showed that HLA-DRB1 alleles that were positively associated with persistent hrHPV showed weaker binding with peptides derived from hrHPV proteins and vice versa. The PRS for persistent hrHPV with the best model fit, had a P-value threshold (PT) of 0.001 and a p-value of 0.06 (-log10(0.06) = 1.22). The findings of this study expand our understanding of genetic risk factors for hrHPV infection and persistence and highlight the roles of MHC class II molecules in hrHPV infection.