High-risk Human Papillomavirus Research Articles

Distribution of 14 High-Risk HPV Types and p16/Ki67 Dual-Stain Status in Post-Colposcopy Histology Results: Negative, Low- and High-Grade Cervical Squamous Intraepithelial Lesions.

Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers. Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ2 test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups. A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ (p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups (p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ (p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups (p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups. The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status.

Electrochemical detection of human papillomavirus DNA based on an ultrasensitive electrochemical sensing platform using N-graphene paper

Human papillomavirus (HPV) is the primary cause of cervical cancer, a major global health concern affecting women worldwide. Early detection of high-risk HPV genotypes is crucial for timely intervention and reducing disease burden. However, current detection methods often lack sensitivity, speed, or cost-effectiveness, especially in resource-limited settings. This work addresses this critical need by developing an ultrasensitive electrochemical biosensing platform based on nitrogen-doped graphene paper electrodes for quantifying high-risk HPV16 DNA sequences. The N-graphene nanohybrid, fabricated via simple solvothermal treatment of biomass-derived graphene oxide, demonstrated significantly enhanced electrical and electrocatalytic properties compared to undoped graphene. DNA detection was achieved through characteristic oxidation signals of guanine bases, which displayed a wide linear dynamic range (0.5–100 μg/mL), low detection limit (75 pg/mL), and excellent reproducibility (relative standard deviation <3.5 %). Detailed spectroscopic and electrochemical analyses revealed the key roles of pyridinic nitrogen defects in improving interfacial charge transfer kinetics and mitigating biofouling issues. This synergistic combination of high electrical conductivity and versatile surface functionality paves the way for equipment-free, point-of-care genosensor devices tailored for quantitative biomarker screening in resource-constrained environments.

Barriers and facilitators for adherence to follow-up by HR-HPV-positive women with premalignant cervical lesions: a mixed-design study in Mexico

BackgroundMexico reports low follow-up completion rates among women with abnormal cervical cancer screenings. This study aimed to identify barriers and facilitators to follow-up adherence among women with human papillomavirus (HPV) infection and premalignant cervical lesions in Mexico.MethodsA mixed-methods study was conducted from February to April 2019. Participants included women undergoing follow-up care for high-risk human papillomavirus (HR-HPV) and premalignant lesions, along with health personnel from the Women’s Healthcare Center (CAPASAM) in Mexico. Quantitative data were obtained from the Women’s Cancer Information System and through a questionnaire about factors affecting follow-up adherence. Additionally, the health personnel involved completed a compliance checklist regarding care regulations. Descriptive statistics were used for analysis. Qualitative data were collected via semi-structured interviews with both groups, followed by a content analysis based on identified categories. The Hazard Analysis and Critical Control Point System confirmed care process risks. Proposals to enhance the Early Detection Program for Prevention and Control of Cervical Cancer were collected from a CAPASAM health personnel nominal group.ResultsIdentified barriers to follow-up included low income among CAPASAM users, family provider roles limiting time for appointments, long waits for testing and results delivery, distant facilities, insufficient service hour communication, inadequate health personnel training, and a lack of systematic counseling. Hesitation toward follow-up was also linked to shame, apprehension, uncertainty, test aversion, fear of positive results, and limited cervical cancer and screening knowledge. Patriarchal attitudes of partners and limited access to the now-discontinued PROSPERA government program further discouraged follow-up. Facilitators comprised respectful treatment by CAPASAM staff, no-cost services, health campaigns, and positive user attitudes.ConclusionsThe study found more barriers than facilitators to follow-up adherence, highlighting the need for strategies to bolster the Early Detection Program. Future strategies must address the comprehensive array of factors and incorporate stakeholder perspectives.

The combination of p16 and Rb expression pattern is helpful to predict high-risk HPV infection and the primary site in lymph node metastases of squamous cell carcinoma

Identifying the primary site of metastatic squamous cell carcinoma in lymph nodes can be challenging. An immunohistochemistry (IHC) analysis recently revealed that high-risk human papillomavirus (HR-HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) typically show overexpression of p16 protein and a partial loss pattern of Rb. Nevertheless, the status of these markers in metastatic lesions is still unclear. In this study, we examined p16 and Rb expression status by IHC and transcriptionally active HR-HPV infection by mRNA in situ hybridization in paired primary and metastatic SCC lesions. A total of 50 patients with OPSCCs (n=17), hypopharyngeal SCCs (n=16), laryngeal SCCs (n=6), or uterine cervical SCCs (n=11) were enrolled. HR-HPV and p16 were positive in 21/50 (42 %) and 23/50 (46 %) patients, respectively. Primary and metastatic lesions showed concordant results for those three markers in individual patients. Among the p16-positive patients (n=23), HPV-positive cases typically showed a partial loss of Rb (n=20) and, rarely, a complete loss of Rb (n=1), whereas HPV-negative cases showed preserved Rb expression (n=2). All 27 p16-negative cases lacked HPV infection, while preserved expression and complete loss of Rb were observed in 26 and 1 of the p16-negative cases, respectively. Compared to standalone p16, the combination of p16 overexpression and Rb-partial/complete loss showed equally excellent sensitivity and negative predictive value (each 100 %) as well as improved specificity (100 % versus 93.1 %) and positive predictive value (100 % versus 91.3 %). Our results suggest that combining p16 and Rb expression patterns may be helpful in screening for HR-HPV infection in metastatic lymph nodes and in estimating the primary site of SCC.

Comparing visual inspection with acetic acid, with and without Lugol’s Iodine for triage of HPV self-sample positive women in Ethiopia: a randomized controlled trial

BackgroundMost women who are high-risk human papilloma virus (hrHPV) positive in a cervical cancer screening test will spontaneously heal from their infection. Visual inspection with acetic acid (VIA) is recommended...

Prevalence and concordance of penile, anal, and oral human papillomavirus infections among sexually active heterosexual men in Ibadan, Nigeria.

The data on epidemiology of Human papillomavirus (HPV) infections in men are scarce relative to women generally, particularly among men engaging in heterosexual relationships. This study investigated the prevalence and risk factors for penile, anal, and oral HPV in men in two communities in Ibadan, Nigeria. This was a cross-sectional survey involving a face-to-face interview, a clinical examination, and sample collection from participants. HPV genotyping was performed with Anyplex II 28 HPV assay. The prevalences and factors associated with HPV infections using multivariable models and concordance between sites. Of 316 men, the proportion of any HPV infection in the penile, anal, and oral sites was 40.5%, 9.7%, and 7.8%, respectively. The proportion of any high-risk HPV, low-risk HPV, and multiple HPV infections was highest in the penis followed by the anal and oral sites. Only 5/316 (1.6%) men had concordant HPV in all three sites, with the highest concordance in penile-anal sites relative to penile-oral and anal-oral sites. The odds of penile HPV were higher in men aged 25years and above. Having penile HPV was associated with higher odds of detecting anal HPV and vice versa. Oral HPV was less likely in men not living with their sexual partners. Penile HPV is the most common infection followed by anal HPV and oral HPV infections among heterosexual Nigerian men. Concordant HPV infections was highest in penile-anal sites. Nigerian men, as in other settings, are a reservoir of HPV and it is important to conduct more robust studies to appreciate their role in HPV transmission, epidemiology, and prevention.

Clinical validation of the Roche cobas HPV test on the Roche cobas 5800 system for the purpose of cervical screening.

This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.

Effect of Clinicopathological Characteristics on the Outcomes of Topical 5-Aminolevulinic Acid Photodynamic Therapy in Patients with Cervical High-Grade Squamous Intraepithelial Lesions (HSIL/CIN2): A Retrospective Cohort Study.

Minimally-invasive 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is used for treating cervical high-grade squamous intraepithelial lesions (HSIL/CIN2). The purpose of this study was to analyze the factors affecting the efficacy of ALA-PDT in the treatment of cervical HSIL/CIN2 in order to guide physicians in making appropriate treatment decisions. A retrospective study including 69 female patients with pathologically diagnosed HSIL/CIN2 was conducted. Patients were given six doses of 20% ALA-PDT at 7-14-day intervals. Cytology, HPV testing, colposcopy, and pathology were performed before treatment and at 6-month follow-up after treatment to assess efficacy. The main outcome of this study was the regression of HSIL/CIN2 and the clearance of high-risk HPV (hrHPV) infection after ALA-PDT treatment. Clinicopathological characteristics were collected to analyze the factors affecting the effectiveness of ALA-PDT treatment for HSIL/CIN2. Between the successful and failed lesion regression group, there was a significant difference in sleeping disorders (p < 0.05). Between the successful and failed hrHPV clearance group, no statistically significant factors were found. With sensitivity values of 0.556 and 0.778, respectively, multivariate analysis showed that current smoking and sleeping disorders were independent prognostics of failure in lesion regression after ALA-PDT treatment. Smoking and sleep disorders were independent risk factors for failure in HSIL/CIN2 regression following ALA-PDT, suggesting the need for careful consideration of ALA-PDT for patients with these conditions.

High-risk HPV mRNA testing on self-samples offered to those who do not attend for organised cervical screening – real world data from the Dumfries and Galloway region in Scotland

BackgroundHPV self sampling can act as a tool to engage women in cervical screening and population based studies can inform optimal implementation of this approach. MethodsSelf sampling kits were mailed to women who had defaulted from routine screening resident in an entire territorial health board in Scotland. Kit return rates and compliance to colposcopy follow up in those who were HPV mRNA positive were assessed. Concordance of the self-sample with samples taken later at colposcopy was measured alongside PPV of an mRNA positive result for CIN2+. ResultsOf 4173 women invited to participate, 20.5 %, returned their kit and a greater return rate with increasing age was observed. HPV mRNA positivity was 12.0 %, and invalidity rate was approximately 3 %. Compliance to colposcopy follow up was 88.3 % and the PPV for an mRNA test for CIN2+ on a self sample was 25.6 %. hr-HPV concordance on the initial swab and the follow up swab and liquid based cytology (LBC) sample taken at colposcopy was 67.1 % and 30 % respectively. ConclusionsHPV self sampling using a “mail to all” approach is feasible in Scotland although only 1 in 5 actively responded to the offer. Future work to monitor screening behaviours in those who were invited but did not engage initially will help quantify any additional benefit(s) incurred.

B-305 High-risk HPV Scenario Among Young People: Data From a Clinical Laboratory (2019-2023)

Abstract Background Human papillomavirus (HPV) infection is the most common sexually transmitted infections and occurs early after the start of sexual life. There are more than 150 types of HPV, classified considering the affected area, symptoms, and oncogenic potential. The types of HPV that cause cancerous lesions are classified as high-risk HPV types. HPV is the main cause of cervical cancer in women and is strongly associated with penile cancer in men. Despite the existence of vaccination, it is still not easily accessible to the entire population of Brazil. In this context, the authors are periodically analyzing the positivity of high-risk HPV infection in secretion and cell scraping samples. Methods 14,806 results were analyzed from a laboratory in São Paulo/Brazil. 4,935 real-time PCR tests were carried out from January/2019 to December/2023 for the detection of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 high risk types. In this study, there was a special focus on HPV types 16 and 18, as they are the main high-risk types for cervical cancer. The other high-risk genotypes were detected, but not differentiated. Results The most ages affected by the infection in both sexes were 25 to 40 years old. Infections with other high-risk types HPV were more frequent in relation to types 16 and 18, Table 1. Conclusions Although the male population represented only 1.19% of processes tests, a higher frequency of HPV positive results was detected (9.04%) compared to female patients (7.55%).

B-338 Real-world data shows the effectiveness of a tetravalent vaccine against Human Papilloma Virus types 16 and 18 in Chilean women

Abstract Background Cervical uterine cancer (CUCa) is the fourth most common female neoplasm globally. At least 99% of CUCa cases are caused by persistent infection of high-risk Human Papillomavirus (HR-HPV) types. In 2014, Chile began a mandatory immunization plan for 9-year-old girls with the GARDASIL™ vaccine, which confers immunity against types 16 and 18 that cause about 70% of CUCa. This work aims to estimate this vaccine's effectiveness in women after nine years of inoculation. Methods We evaluated the results for HPV detection from 21.676 women between 15 and 77 years old between 2019 and 2023 at Bupa Lab. HPV detection and genotyping was performed with the ROCHE Cobas® HPV Test. Effectiveness was measured as the ratio between the number of cases of HPV types 16+18 versus other HR-HPV. Results During the analyzed period, the number of tests performed increased significantly, and the positivity rate decreased from 44% in 2019 to 26,9% in 2023. Global positivity was 32% for some HR-HPV types, reaching a peak of 49,5% in the 20 to 24,9 years group. The average 16+18/other HR ratio was 0,39, which decreased significantly to 0,24 in the vaccinated group of women between 15 and 19,9 years, suggesting an effectiveness of 37,5% against HPV types 16 and 18 concerning the total HR types (Table 1). Conclusions In recent years, HPV detection has proven useful in preventive monitoring and early detection of CUCa. This increased awareness has triggered a significant rise in HPV testing and could be driving test positivity downwards. Although a more appropriate study design is required to estimate the actual effectiveness of the vaccine in Chile, our analyses showed a significant decrease in HPV types 16 and 18 in women after nine years of vaccination, which represents a crucial advance toward the eradication of CUCa.

B-353 High risk HPV genotypes prevalence in Mexico

Abstract Background The greatest risk factor for the development of cervical cancer is infection by human papillomavirus (HPV). To date, more than 200 genotypes have been described, 14 of them considered by the WHO as high risk genotypes (HR) due to their high oncogenic capacity, with special attention given to genotypes 16 and 18. In Mexico, cervical cancer is the third cause of cancer-associated death in women, therefore, the timely detection of HR genotypes in women becomes imperative for the reduction of the burden of this disease. The detection of high-risk HPV genotypes through the PCR molecular test is part of primary cervical cancer screening, however, this practice is not common in Mexico. Here, we analyzed the results of HPV genotyping studies in women attending cervical cancer screening studies at Salud Digna with the objective of determining the prevalence and dsitribution of HR-HPV in Mexico. Methods Retrospective analysis of the results obtained for the detection of HPV in cervical samples from patients who were attended at Salud Digna clinics from june to august 2023. The samples were processed by automated RT-PCR (ROCHE COBAS PRIME-Cobas 6800). The kit used was the COBASHPV which detects the 14 HR genotypes and generates 4 types of results: negative, positive for HPV16, positive for HPV18 and positive for POOL (which includes the remaining 12 genotypes). For the analysis, Mexico was divided into 7 regions which share sociocultural factors (Northwest, North, West, Center, Gulf, South, Southeast). Results The study population was 95,934 patients (mean age of 41y). At the national level, 18.93% (18,159) of patients are positive for HPV POOL, 3.54% (3,399) for HPV 16 and 1.78% (1709) for HPV 18. The regions with the highest positivity are the southeast region for HPV POOL (22.32%), the south region for HPV 16 (3.77%) and HPV 18 (2.44%) while the region with the lowest percentage is the Northwest region (HPV POOL 17.86%, HPV16 3.39%, HPV18 1.57%). The age range with the highest percentage of positivity is 14-29y for HPV POOL, 30-39y for HPV 16, and 30-39y for HPV 18. Conclusions We found that Mexican patients are becoming infected at an early age with the genotypes that are part of the pool, however, we observe a marked trend towards a decrease in cases as the age of the population advances.The regions of the country with a higher percentage of HPV positive patients are the south and the southeast, regions that also concentrate most of the extreme poverty in Mexico. These numbers should be taken with caution given that in absolute values these are also are the regions of the country where the least people go for a cervical cancer screening study, emphasizing the need to promote these studies in these regions. In the case of genotypes with a greater oncogenic capacity, both HPV16 and HPV18 show a greater prevalence in economically productive age ranges. Retrospective studies like provide information that allow governments to generate public policies focused on the most affected regions.

Viral whole genome sequencing reveals high variations in APOBEC3 editing between HPV risk categories.

High-risk human papillomavirus (HPV) infections are responsible for cervical cancer. However, little is known about the differences between HPV types and risk categories regarding their genetic diversity and particularly APOBEC3-induced mutations - which contribute to the innate immune response to HPV. Using a capture-based next-generation sequencing, 156 HPV whole genome sequences covering 43 HPV types were generated from paired cervical and anal swabs of 30 Togolese female sex workers (FSWs) sampled in 2017. Genetic diversity and APOBEC3-induced mutations were assessed at the viral whole genome and gene levels. Thirty-four pairwise sequence comparisons covering 24 HPV types in cervical and anal swabs revealed identical infections in the two anatomical sites. Differences in genetic diversity among HPV types was observed between patients. The E6 gene was significantly less conserved in low-risk HPVs (lrHPVs) compared to high-risk HPVs (hrHPVs) (p = 0.009). APOBEC3-induced mutations were found to be more common in lrHPVs than in hrHPVs (p = 0.005), supported by our data and by using large HPV sequence collections from the GenBank database. Focusing on the most common lrHPVs 6 and 11 and hrHPVs 16 and 18, APOBEC3-induced mutations were predominantly found in the E4 and E6 genes in lrHPVs, but were almost absent in these genes in hrHPVs. The variable APOBEC3 mutational signatures could contribute to the different oncogenic potentials between HPVs. Further studies are needed to conclusively determine whether APOBEC3 editing levels are associated to the carcinogenic potential of HPVs at the type and sublineage scales.

Recombinant adenoviruses expressing HPV16/18 E7 upregulate the HDAC6 and DNMT3B genes in C33A cells.

High-risk human papillomavirus (HPV) is a carcinogenic virus associated with nearly all cases of cervical cancer, as well as an increasing number of anal and oral cancers. The two carcinogenic proteins of HPV, E6 and E7, can immortalize keratinocytes and are essential for HPV-related cellular transformation. Currently, the global regulatory effects of these oncogenic proteins on the host proteome are not fully understood, and further exploration of the functions and carcinogenic mechanisms of E6 and E7 proteins is needed. We used a previously established platform in our laboratory for constructing recombinant adenoviral plasmids expressing the HPV16 E7 gene to further construct recombinant virus particles expressing HPV16/18 E6, E7, and both E6 and E7 genes. These recombinant viruses were used to infect C33A cells to achieve sustained expression of the HPV16/18 E6/E7 genes. Subsequently, total RNA was extracted and RNA-Seq technology was employed for transcriptome sequencing to identify differentially expressed genes associated with HPV infection in cervical cancer. RNA-Seq analysis revealed that overexpression of the HPV16/18 E6/E7 genes upregulated GP6, CD36, HDAC6, ESPL1, and DNMT3B among the differentially expressed genes (DEGs) associated with cervical cancer. Spearman correlation analysis revealed a statistically significant correlation between the HDAC6 and DNMT3B genes and key pathways, including DNA replication, tumor proliferation signature, G2M checkpoint, p53 pathways, and PI3K/AKT/mTOR signaling pathways. Further, qRT-PCR and Western blot analyses indicated that both HPV16/18 E7 can upregulate the expression of HDAC6 and DNMT3B, genes associated with HPV infection-related cervical cancer. The successful expression of HPV16/18 E6/E7 in cells indicates that the recombinant viruses retain the replication and infection capabilities of Ad4. Furthermore, the recombinant viruses expressing HPV16/18 E7 can upregulate the HDAC6 and DNMT3B genes involved in cervical cancer pathways, thereby influencing the cell cycle. Additionally, HDAC6 and DNMT3B are emerging as important therapeutic targets for cancer. This study lays the foundation for further exploration of the oncogenic mechanisms of HPV E6/E7 and may provide new directions for the treatment of HPV-related cancers.

Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

Referral tertiary care hospital for adult patients with cancer. We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

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.

[Translated article] Retrospective Study of Risk Markers for Developing High-Grade Anal Intraepithelial Neoplasm in Men Who Have Sex With Men Living With HIV

BackgroundHigh-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition—the precursor to anal cancer—significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. Materials and methodsTo describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study. ResultsNinety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DiscussionIn this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. ConclusionIn men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status: 5-year follow-up of a prospective cohort study

ObjectiveWe investigated the relation man papillomavirus (HPV) integration status and the immediate risk of cervical intraepithelial neoplasia (CIN), as well as the triage strategy based on HPV integration test. Methods4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective, population-based, clinical observational study to evaluate the triage performance of HPV integration. Cervical exfoliated cells were collected for HPV testing and cytologic test. If high-risk HPV was positive, HPV integration test was performed at baseline, 2-year and 5-year follow-up. ResultsAt baseline, HPV integration was positively correlated with the severity of cervical pathology, ranging from 5.0% (15/301) in normal diagnosis, 6.9% (4/58) in CIN1, 31.0% (9/29) in CIN2, 70% (14/20) in CIN3, and 100% (2/2) in cervical cancer (P < 0.001). Compared with cytology, HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+, higher specificity (92.8% [90.2%–95.4%] vs. 75.5% [71.2%–79.8%], P < 0.001) and higher positive predictive value (36.4% [22.1%–50.6%] vs. 15.2% [8.5%–21.8%], P < 0.001). HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy (10.7% [44/410] vs. 27.3% [112/410], P < 0.001). The HPV integration-negative group exhibited the lowest immediate risk for CIN3+ (1.6%) and accounted for the largest proportion of the total population (89.3%), when compared with the normal cytology group (risk, 1.7%; proportion, 72.7%). ConclusionAs a key molecular basis for the development of cervical cancer, HPV integration might be a promising triage strategy for HPV-positive patients.

P21-3 A pilot study on miRNA detection in residual of liquid-based high-risk genotype HPV samples for ovarian cancer diagnosis

P21-3 A pilot study on miRNA detection in residual of liquid-based high-risk genotype HPV samples for ovarian cancer diagnosis

The Sansure® Human Papillomavirus DNA Diagnostic Kit offers excellent reproducibility performance for the detection of high-risk HPV.

Cervical cancer screening is a cornerstone of cervical cancer elimination. Detection of high-risk human papillomavirus (hrHPV) is recommended as the first step in screening provided that the assay used has been adequately validated. The Sansure® Human Papillomavirus DNA Diagnostic Kit is a new assay designed to detect HPV16, HPV18 and 13 other HPV in aggregate. The study aimed to evaluate the intra- and interlaboratory reproducibility of the assay according to international guidelines. Five hundred and fifty cervical residual cell samples from women attending cervical cancer screening were selected from the biobank of the HPV National Reference Centre in Belgium and used in this study. After DNA extraction, HPV was tested using the Sansure® Human Papillomavirus DNA Diagnostic Kit. The lower 95% confidence limit around the general reproducibility of this assay should be greater than or equal to 87%, with κ ≥ 0.50. Five hundred and thirty-three samples had valid results. The Sansure® Human Papillomavirus DNA Diagnostic Kit demonstrated an excellent intra-laboratory reproducibility of 93.8% (95% confidence interval [CI]: 91.4-95.7, κ = 0.85). The interlaboratory reproducibility was 93.4 (95% CI: 91.0-95.4, κ = 0.84). Intra and interlaboratory reproducibility were also excellent at the genotype level. Excluding HPV53 single infection samples from the analyses also resulted in excellent agreement. These data show that the Sansure® Human Papillomavirus DNA Diagnostic Kit is highly reproducible.