Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study.

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

The cervical cancer related distribution, coinfection and risk of 15 HPV types in Baoan, Shenzhen, in 2017-2023.

Cervical cancer is one of the most common malignant tumours. Human papillomavirus (HPV) infection is the main cause of this cancer so that it could be prevented by screening and early treatment. Developing reginal screen protocols of maximum public health efficacy requires in-depth understandings of local HPV distribution and consequential cancer risks. Therefore, test results of HPV genotyping, cytology testing (TCT) and colposcopy inspection with biopsy were collected in this retrospective research. Data included by this research involved 63,906 women received screen related tests from Shenzhen Baoan Shiyan People's Hospital and the subsidiary institutes between 2017.01 and 2023.05. 10,238 colposcopies were performed in this period collecting 8,716 samples and 814 high-grade CIN were discovered. Within the 763 high-grade CIN cases with both TCT and HPV testing results, 232 were tested cytologically normal but only 30 were negative in HPV test. Besides, the rates of high-grade CIN observed in coinfection were all lower than the estimated rates generated from related single infection. HPV 52, 58 and 16 were found to be the most common types in Baoan, Shenzhen. The result also suggested that HPV coinfections should not increase risk for cervical cancers.

The Rare Condition of a Double Cervix: Results from the High-Risk Human Papillomavirus-Based Cervical Cancer Screening Program in the Lazio Region.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate HR-HPV infections in women with a double cervix within the National Cervical Cancer Screening program of the Lazio region (Italy). From June 2021 to March 2024, a total of 142,437 samples were analyzed by Seegene's Anyplex TM II HR-HPV method, which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervices and analyzed separately. Twenty-seven women with a double cervix were identified (0.019%): 23 women were tested as negative for both cervices, while the remaining four (namely A, B, C, and D) resulted positive. By genotyping, the following results were obtained: (A) Both samples showed genotype 31; (B) one cervix was negative while the other showed genotype 58; (C) one cervix was positive for HPV 18 and 31 while for 18, 31, and 33 in the other; and (D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition where the presence of HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.

HPV Infections-Classification, Pathogenesis, and Potential New Therapies.

To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines.

Study on the detection rate, genetic polymorphism, viral load, persistent infection capacity, and pathogenicity of human papillomavirus type 81.

Human papillomavirus (HPV) type 81 has recently become one of the most common low-risk HPV types; however, literature focusing on it is limited. This study aimed to analyze the reasons for the increased detection rate of HPV81 and investigate its evolving pathogenicity. We analyzed the detection rates and trends of HPV81 in 229 061 exfoliated cervical cell samples collected from 2014 to 2023; collected samples of HPV81 single infections from two different time periods; and analyzed the allele frequencies, positive selection, viral load, persistent infection capacity, and pathogenicity of E6 and E7 genotypes. We found that the detection rate of HPV81 ranked first among the low-risk types in exfoliated cervical cells and exhibited a significantly increasing trend (p < 0.001). The frequency of the E6 prototype allele of HPV81 (n = 317) was significantly increased (p = 0.018) and demonstrated the strongest adaptive capacity. The viral load and persistent infection capacity of the E6 prototype were significantly higher than those of the mutants, thus serving as key drivers for increasing the detection rate of HPV81 and enhancing its pathogenicity. The viral load was positively correlated with persistent infection capacity and pathogenicity. Persistent infection was a crucial factor in the pathogenicity of HPV81. Successful adaptive evolution of HPV81 is accompanied by enhanced pathogenicity.

Proof of Concept Study: Comparability of Microbiome Diversity in Self- and Physician-Collected HPV-Positive and HPV-Negative Cervicovaginal Samples.

Recent studies have revealed the impact of human papillomavirus (HPV) infections on the cervicovaginal microbiome; however, few have explored the utility of self-collected specimens (SCS) for microbiome detection, obtained using standardised methods for HPV testing. Here, we present a proof-of-concept analysis utilising Oxford Nanopore sequencing of the 16S rRNA gene in paired samples collected either by the patient using an Evalyn Brush or collected by a physician using liquid-based cytology (LBC). We found no significant differences in the α-diversity estimates between the SCS and LBC samples. Similarly, when analysing ß-diversity, we observed a close grouping of paired samples, indicating that both collection methods detected the same microbiome features. The identification of genera and Lactobacillus species in each sample allowed for their classification into community state types (CSTs). Notably, paired samples had the same CST, while HPV-positive and -negative samples belonged to distinct CSTs. As previously described in other studies, HPV-positive samples exhibited heightened bacterial diversity, reduced Lactobacillus abundance, and an increase in genera like Sneathia or Dialister. Altogether, this study showed comparable results between the SCS and LBC samples, underscoring the potential of self-sampling for analysing the microbiome composition in cervicovaginal samples initially collected for HPV testing in the context of cervical cancer screening.

Increased human papillomavirus viral load is correlated to higher severity of cervical disease and poorer clinical outcome: A systematic review.

Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer.

Species-level characterization of the cervicovaginal microbiota and its role in human papillomavirus-associated cervical carcinogenesis.

The cervicovaginal microbiome may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis, but studies have been limited by low-resolution analysis methods. Using a high-resolution bioinformatics pipeline, we evaluated the relationship of the cervicovaginal microbiome with HPV and cervical intraepithelial neoplasia (CIN). The cervicovaginal microbiome of 186 women was characterized by sequencing 16S rRNA regions (V3-V4 and V5-V6) and annotated with the high-resolution ANCHOR pipeline. Samples were genotyped for HPV using the Roche-Cobas 4800 assay. We fitted logistic regression models using stepwise forward selection to select species (presence/absence) as correlates of CIN1+ and constructed a linear microbiome-based score using the regression coefficients. An HPV-based score was calculated from a separate logistic regression model to detect CIN1+ . Receiver operating characteristic curve analyses were performed; the area under the curve (AUC) and 95% confidence intervals (CI) were compared between scores. Overall, 66.7% of participants were HPV-positive. 77 unique species were identified: 8 using V3-V4, 48 using V5-V6, and 21 shared. Twelve species were retained via stepwise selection. The AUCs for the microbiome-, and HPV-based scores were 0.7656 (95% CI 0.6885-0.8426), and 0.7529 (95% CI 0.6855-0.8204), respectively. Bacterial species may be involved in cervical carcinogenesis as the microbiome- and HPV-based scores performed similarly for CIN1+ detection.

Factors Associated with HPV Genital Warts: A Self-Reported Cross-Sectional Study among Students and Staff of a Northern University in Nigeria.

The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to a free HPV vaccine is a public health concern. HPV is one of the most common sexually transmitted infections (STIs) in Nigeria, while the most known types of HPV genotypes being transmitted are the high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) University located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on Google Forms and it was distributed to the university community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, and knowledge about HPV infection and genotypes, as well as the sexual health of the participants. All variables were described using frequencies and percentage distribution; chi-squared test statistics were used to explore the association between HPV infection (medical records of HPV infection) and the participants' profile, and a logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26-40 years (81.3%) and those currently not in a sexually active relationship-single/divorced (26.4%)-who have self-reported having the HPV-16 and -18 genotypes. Moreover, participants between 26-40 years of age (OR: 0.45, 95%CI: 0.22-0.89) reported themselves to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.

The prevalence and genotype distribution of high-risk human papillomaviruses among women in Xianning, China.

BACKGROUND: The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically. METHODS: Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China's National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed. RESULTS: A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively. CONCLUSION: HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work.

Prevalence and Genotype Distribution of HPV in Hangzhou, China.

BACKGROUND: For women, cervical cancer is the most prevalent cancer and the most common cause of cancer-related deaths worldwide. Human papillomavirus (HPV) is causatively linked to over 90% of cervical cancer cases. Our retrospective study explored the clinical and laboratory data of outpatients with HPV infection to analyze the prevalence and genotype distribution of 3,793 outpatients in the Hangzhou area by using HPV genotype tests. It could provide value for an effective prevention and treatment of HPV infection. METHODS: In total, 3,793 female outpatients were randomly selected from January 2022 to December 2023. Exfoliated cervical cells were collected using a cytobrush and HPV genotype screening was conducted for testing. Data of all outpatients were collected from the hospital's electronic medical records, and SPSS 26.0 software was used to perform the statistical analysis. RESULTS: Out of 3,793 outpatients, 953 were detected as positive, and the positive rate was 25.13%. The age of the outpatients ranged from 15 - 97, with an average age of 39.91. All outpatients were divided into six age groups. Among the six age groups, the HPV positive rates were, with ascending age, 43.90%, 33.27%, 21.49%, 16.99%, 27.30%, and 25.48%, and the highest positive rate was observed in those aged  20 with a rate of 43.90%. There were significant differences in the positive rates among different age groups (p < 0.05). There were more outpatients with a single infection than with multiple infection (p < 0.05). The positive rate of single infection was the highest in the 31 - 40 and 41 - 50 age groups (74.32% for both) and the positive rate of multiple infection was the highest in the  20 age group (66.67%). Among 24 genotypes, HPV 52, 58, and 51 were the most commonly detected. All three were high-risk genotypes, and HPV 52 was the most dominant in all age groups. As distribution according to quarter, more HPV infection occurred in the fourth quarter, which had a significant difference (p < 0.05). And in the first quarter, the number of HPV positive infections was the lowest. CONCLUSIONS: Prevalence and genotype distribution of HPV in the Hangzhou area were different from those of other regions. More single infection, and more multiple infection occurring in low age and in the fourth quarter were the characteristics of HPV infection in the Hangzhou area. It was suggested that vaccine containing HPV 52 might be a better choice for this region.

Comparative evaluation of HPV genotyping: A study on the performance concordance between Anyplex II HPV28 detection and Linear Array genotyping tests in nationwide studies in Brazil.

BACKGROUND: Advances in laboratory techniques for HPV diagnosis necessitate a thorough assessment of the efficiency, replicability, sensitivity, and specificity of those methods. This study aims to validate and compare HPV detection/genotyping using the Anyplex™ II HPV28 Detection assay (Seegene) assay and the Linear Array HPV Genotyping test (Roche Diagnostics) on genital samples for use in epidemiological studies. METHODS: From 6,388 penile and cervical DNA samples collected in the POP-Brazil, 1,745 were randomly selected to be included in this study. The samples were submitted to HPV detection and genotyping following the manufacturers' protocols. DNA was genotyped using the Anyplex™ II HPV28 Detection kit (Seegene), and the results were compared to those obtained using the Linear Array HPV Genotyping test (Roche Diagnostics). Concordance of HPV genotyping results was assessed by the percentage agreement and Cohen's kappa score (κ). RESULTS: The agreement between the two methodologies was deemed good for HPV detection (κ = 0.78). Notably, Anyplex™ II HPV28 demonstrated enhanced capability in detecting a broader spectrum of genotypes compared to Linear Array. CONCLUSION: Anyplex™ II HPV28 exhibited comparable results to the Linear Array assay in clinical specimens, showcasing its potential suitability for a diverse array of research applications requiring the detection and genotyping of HPV. The study supports the utility of Anyplex™ II HPV28 as an effective tool for HPV screening in epidemiological studies, emphasizing its robust performance in comparison to established diagnostic tests.

Prevalence characteristics of cervical human papillomavirus infection in Chengdu and Aba District, Sichuan Province, China.

PURPOSE: The genotype distribution of human papillomavirus (HPV) infection varies greatly in different regions. This study aims to determine the prevalence and type-specific distribution of HPV among females from Chengdu and Aba in Sichuan Province, which differ in geographical location, economic status, and living habits. These can serve as evidence of epidemic patterns for future design and implementation of vaccination and screening programs. METHODS: A retrospective cross-sectional study was conducted on 144 113 women who underwent cervical screening at Chengdu Women's and Children's Central Hospital from January 2015 to September 2020. Meanwhile, 1799 samples from February 2018 to December 2021 were collected from Aba Maternal and Child Health Hospital. HPV DNA genotype testing was performed using real-time PCR. The overall prevalence, annual trend, age-specific prevalence, and type distribution were analyzed. RESULTS: The overall HPV prevalence was 22.51% in Chengdu. During 2015-2020, the highest prevalence rate was observed in 2018. Age-specific HPV distribution displayed a bimodal distribution among women aged ≤25 or ≥46 years old. The top three prevalent genotypes were HPV52, -16, and -58. Although the total prevalence of HPV in Aba was 14.23%, there was an upward trend from 2018 to 2021. However, no significant differences were identified in HPV infection rate across all age groups. HPV52, -53, and -16 were the major genotypes. Furthermore, single-type HPV infections and high-risk HPV infections were identified as the most common infection types in both regions. CONCLUSION: Our findings demonstrate the overall prevalence of HPV was still high in Chengdu and Aba. The age-specific prevalence distribution demonstrated different patterns. Non-vaccine-covered HR-HPV53, -51and LR-HPV81, -CP8304 were frequently detected, which was worth significant clinical attention. In summary, regional HPV screening provides valuable clinical guidance for cervical cancer prevention and vaccine selection in Western China.

Temporal composition of the cervicovaginal microbiome associates with hrHPV infection outcomes in a longitudinal study.

BACKGROUND: Persistent infections with high-risk human papillomavirus (hrHPV) can cause cervical squamous intraepithelial lesions (SIL) that may progress to cancer. The cervicovaginal microbiome (CVM) correlates with SIL, but the temporal composition of the CVM after hrHPV infections has not been fully clarified. METHODS: To determine the association between the CVM composition and infection outcome, we applied high-resolution microbiome profiling using the circular probe-based RNA sequencing technology on a longitudinal cohort of cervical smears obtained from 141 hrHPV DNA-positive women with normal cytology at first visit, of whom 51 were diagnosed by cytology with SIL six months later. RESULTS: Here we show that women with a microbial community characterized by low diversity and high Lactobacillus crispatus abundance at both visits exhibit low risk to SIL development, while women with a microbial community characterized by high diversity and Lactobacillus depletion at first visit have a higher risk of developing SIL. At the level of individual species, we observed that a high abundance for Gardnerella vaginalis and Atopobium vaginae at both visits associate with SIL outcomes. These species together with Dialister micraerophilus showed a moderate discriminatory power for hrHPV infection progression. CONCLUSIONS: Our results suggest that the CVM can potentially be used as a biomarker for cervical disease and SIL development after hrHPV infection diagnosis with implications on cervical cancer prevention strategies and treatment of SIL.

Risk of cervical high-grade squamous intraepithelial neoplasia in cytologic negative and persistently high-risk human papillomavirus positive patients according to genotypes: a retrospective single center analysis.

In January 2020, a different cervical cancer screening program started in Germany. Women above the age of 35 are recommended to have a combined HPV and cytology swab every three years. Showing persistent high-risk human papillomavirus (hrHPV), cytologic negative cervical samples at baseline and after 12 months, patients are referred to colposcopy. Entailing considerable additional workload due to the required colposcopies, we analyzed the risk of high-grade cervical intraepithelial neoplasia (CIN 3) in cytologic negative and persistent hrHPV women according to their hrHPV genotypes.Methods In this single center retrospective study, patients with persistent hrHPV, cytology negative cervical samples from our certified Colposcopy Unit in 2020 and 2021 were analyzed. Patient demographics, hrHPV types, biopsy rates and histological reports were collected.Results During the study, 69 patients were enrolled. Most frequent hrHPV genotypes were: hrHPV other 72.5%; HPV 16, 20.3% and HPV 18, 7.2%. Colposcopy showed no or minor changes in 92.7% and major changes in 7.2%. CIN 3 was found in 7 patients (10.1%). Prevalence of CIN 3 by hrHPV genotypes was 27.3% for HPV16, 20.0% for HPV18 and 7.1% for HPVO. A statistically significant dependency between hrHPV and cervical intraepithelial neoplasia was demonstrated (p = 0.048).Conclusion Within this single center study of persistent hrHPV, cytologic negative samples, patients with HPV 16 were more likely to have high-grade disease compared to other hrHPV subtypes. Larger prospective randomized trials are needed to substantiate our results and obtain adjusted cervical cancer screening time intervals according to the hrHPV genotypes.

Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review.

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Distribution and Severity of Cervical Intraepithelial Neoplasia in Women With Different Human Papillomavirus: An Analysis From Liaoning Province of Northeastern China.

OBJECTIVE: Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. MATERIALS AND METHOD: We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. RESULTS: Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. CONCLUSIONS: The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.

Key aspects of papillomavirus infection influence the host cervicovaginal microbiome in a preclinical murine papillomavirus (MmuPV1) infection model.

Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female FVB/N mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.IMPORTANCEHuman papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.