BMC Infectious Diseases

Unveiling the burden of human papillomavirus infection and risk factors among Indigenous women in Mizoram, Northeast India

Human papillomavirus (HPV) infection is a significant public health concern globally, with its burden increasing in regions with limited access to screening and preventive measures. Understanding how HPV affects different populations is crucial, genetic background, behavioral factors, sexual health practices, co-infections, and access to screening and vaccination services significantly influence disease dynamics, prevalence of high-risk genotypes, and progression to malignancies such as cervical cancer. Such variations underscore the importance of region-specific epidemiological studies and serve as key predictors which can impact the well-being of the population. The study aims to investigate the prevalence and burden of HPV and its association with different risk factors among the indigenous Mizo women of Mizoram, Northeast India. This cross- sectional study was conducted among 1018 women age (20-73 years) from November 2023 to 2024 from different districts in Mizoram. Cervical swabs were collected in VTM after obtaining consent from the patients as well as the demographic and clinical data via a questionnaire. DNA-based HPV genotyping and Pap smear analysis were performed. Statistical analysis was performed by using SPSS version 22.0 software to determine the association between HPV and the risk factors. Out of the 1018 participants, findings revealed a 14.9% overall prevalence of HPV infection, with most participants being from the district capital, Aizawl (78.7%). Age group 51-60 years age group had a notable proportion of HPV-positive individuals (11.5%), they exhibited significantly lower odds of HPV infection compared to younger age groups (OR = 0.155, 95% CI: 0.038-0.632; p = 0.009). Most participants were married (93.3%) with 78.5% being housewives. Among different occupations, participants employed in government sectors have a higher odds ratio 1.898 of HPV infection suggesting potential occupational or lifestyle-related influence on infection risk. Key lifestyle factors such as betel nut consumption and early sexual debut are associated with increased infection risk. Cervicitis, chronic pelvic pain and multiple pregnancies were significant clinical indicators. Ingestion of oral contraceptives were less likely to be HPV positive than were those who did not ingest them (OR: 0.604, Cl: 0.399-0.915; p = 0.017). Pap smear results revealed associations with high-grade squamous intraepithelial lesions (p = 0.025). Genotypes HPV-16 (26.97%) and HPV-18 (17.11%) were the most prevalent genotypes. Approximately 23.4% of the patients presented with multiple genotype infections. This study underscores the importance of tailored public health strategies for high-risk regions such as Mizoram. These include promoting HPV vaccination, enhancing screening programs, and addressing sociocultural practices contributing to infection risk. While the cross-sectional design, female-only participation, and lack of follow-up limit causal interpretation and generalizability. Comprehensive interventions and awareness campaigns are crucial to mitigate the HPV burden and reduce the incidence of cervical cancer in this unique sociodemographic context.

Chlamydia trachomatis infection seroprevalence among women with normal and abnormal cervical smears and its implication for Nigerian cervical cancer screening

The oncogenic human papilloma virus (HPV) causes transient infections of the cervix, hence other co-factors can potentiate the formation of cervical epithelial cell abnormalities. This study was aimed at determining the seroprevalence of Chlamydia trachomatis infection among women with normal and abnormal Papanicolaou smear cytology results. This was a hospital-based cross-sectional comparative study in which study participants were conveniently recruited from January to June,2021. The 50 cases and 50 controls were women with abnormal and normal Papanicolaou smear cytology results respectively. Both groups had blood samples collected for anti- Chlamydia trachomatis antibody test. The data was analyzed with the Statistical Product and Service Solutions (IBM SPSS, Armonk, New York, USA) version 24.0 for windows. The categorical and continuous variables were analyzed with chi square(X The overall seroprevalence of Chlamydia trachomatis infection was 27%. Positive Chlamydia infection had a significant association with cervical epithelial cell abnormalities (P- value = 0.001). Positive history of multiple sexual partners and coitarche at age of < 18 years were associated factors for Chlamydia trachomatis infection. This study identified an association between history of Chlamydia trachomatis infection and cervical epithelial cell abnormalities.

Association of plasma aflatoxin with persistent detection of oncogenic human papillomaviruses in cervical samples from Kenyan women enrolled in a longitudinal study

Abstract Background Cervical cancer is caused by oncogenic human papillomaviruses (HR-HPV) and is common among Kenyan women. Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of HR-HPV detection in cervical specimens. This analysis was performed to examine associations between aflatoxin and HR-HPV persistence. Methods Kenyan women were enrolled in a prospective study. The analytical cohort for this analysis included 67 HIV-uninfected women (mean age 34 years) who completed at least two of three annual study visits and had an available blood sample. Plasma aflatoxin was detected using ultra-high pressure liquid chromatography (UHPLC)-isotope dilution mass spectrometry. Annual cervical swabs were tested for HPV (Roche Linear Array). Ordinal logistic regression models were fitted to examine associations of aflatoxin and HPV persistence. Results Aflatoxin was detected in 59.7% of women and was associated with higher risk of persistent detection of any HPV type (OR = 3.03, 95%CI = 1.08–8.55, P  = 0.036), HR-HPV types (OR = 3.63, 95%CI = 1.30-10.13, P  = 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (OR = 4.46, 95%CI = 1.13–17.58, P  = 0.032). Conclusions Aflatoxin detection was associated with increased risk of HR-HPV persistence in Kenyan women. Further studies, including mechanistic studies are needed to determine if aflatoxin synergistically interacts with HR-HPV to increase cervical cancer risk.

Association between cervical dysplasia and female genital schistosomiasis diagnosed by genital PCR in Zambian women

Abstract Background Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium , a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. Methods Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18–31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. Results VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58–23.37, P  = 0.02). Conclusions This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed.

Human papillomavirus (HPV) genotype distribution in Malaysia: A systematic review

Abstract Background Human papillomavirus (HPV) is a key etiological factor in cervical cancer in both Malaysia and globally. It continues to pose a significant public health challenge. This systematic review aims to delineate the distribution of HPV genotypes across different demographics in Malaysia to inform targeted prevention strategies. Methods We conducted a systematic review following PRISMA guidelines, analyzing observational studies published from 2000 onward that reported HPV genotypes in cervicovaginal samples from Malaysian women. The review utilized PubMed, SCOPUS, The Cochrane Library, APA PsycNet, and Google Scholar for literature searches, focusing on studies that employed molecular methods for HPV genotyping. Two reviewers independently screened the articles, extracted data, and assessed study quality using the Newcastle-Ottawa Scale (NOS). A descriptive analysis was performed, and findings were synthesized by genotype, region, and ethnicity. Results The review included 22 studies from an initial pool of 2,547 articles, encompassing 44,251 women. These studies reported a HPV prevalence of up to 100% in confirmed cervical cancer cases and in general screenings from 4.5 to 47.7%. A total of 28 different HPV genotypes (high- and low-risk) were identified, with HPV16, HPV18, HPV58, HPV52, and HPV33 being the most prevalent high-risk genotypes. Genotype distributions showed significant variation across different states and ethnic groups within Malaysia, highlighting the diverse nature of HPV-related risks. Conclusions This review provides a detailed snapshot of the HPV genotype distribution in Malaysia, underscoring the necessity for tailored public health interventions that address the regional and ethnic diversity in HPV prevalence. The findings support the need for targeted vaccination programs and enhanced screening measures to effectively combat the high rates of HPV-related (99%) cervical cancer in Malaysia.

Cervical cancer screening service utilisation and related factors among women on antiretroviral therapy in public health facilities of Asella town, Ethiopia, cross-sectional study

Cervical cancer is the predominant form of cancer in Ethiopia, accounting for the majority of malignant cases. Women account for two-thirds of cancer-related deaths in the country. Cervical cancer screening (CCS) can help prevent disease development, but screening rates are unacceptably low. The greatest number of women were in the most vulnerable group, and the availability of wheal data on their use of CCSs was limited. This study aimed to evaluate the use of CCS and the factors that influence its use among HIV-positive women receiving antiretroviral therapy at public health facilities. This study used a cross-sectional study design. A total of 396 (97.5%) HIV-positive women participated in this study between March 10 and May 30, 2023. Participants enrolled in public health facilities in Asella town were selected through systematic random sampling, and data were collected through on-site interviews using a pretested, structured questionnaire. The data were analysed using the Statistical Package for Social Science, Version 26. Logistic regression analysis was used to identify the determining factors. The findings from this study indicated that 30.3% of individuals used cervical cancer screening services. Those women who had knowledge about cervical cancer had a 2.54 times greater likelihood of receiving CCS than those who were not informed (adjusted odds ratio [AOR] = (2.54; 95% confidence interval [CI]: 1.42-4.56). Women with a history of sexually transmitted diseases were twice as likely to use CCS as those without such a history (AOR = 2.05, 95% CI = 1.13-3.73). Furthermore, women with a positive attitude towards CCS were found to be significant predictors of utilisation, showing a greater than threefold greater likelihood of using these services (AOR = 3.21; 95% CI: 1.78-5.81). The proportion of HIV-positive women who underwent cervical cancer screening (CCS) was significantly lower than the recommended guideline of 80%. To enhance the uptake of screening among women with HIV, healthcare professionals should focus on enhancing awareness about cervical cancer, improving attitudes towards CCS, and advancing knowledge about the disease. Healthcare providers' collaboration with both government and nongovernmental stakeholders plays a crucial role in addressing the challenges of accessibility and attendance at screening services.

High frequency of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico

AbstractBackgroundHuman papillomavirus infection is an important factor associated with cervical cancer (CC) development. The prevalence and genotype distribution vary greatly worldwide. Examining local epidemiological data constitutes an important step towards the development of vaccines to prevent CC. In this work, we studied the prevalence of HPV genotypes in women from Western Mexico with the COBAS 4800 and/or Linear Array Genotyping Test (LA).MethodsThe samples analysed in this study represent a population from Western Mexico, which includes six different states. Our approach was first to test for HPV in cervical samples from women who attended their health clinic for routine gynaecological studies (open-population,n = 3000) by utilizing COBAS 4800. Afterwards, 300 of the HPV-positive samples were randomly selected to be genotyped with LA; finally, we genotyped samples from women with cervical intraepithelial neoplasia grade 1 (CIN 1,n = 71) and CC (n = 96) with LA. Sociodemographic data of the diverse groups were also compared.ResultsThe overall HPV prevalence among the open-population of women as determined by COBAS 4800 was 12.1% (n = 364/3000). Among the HPV-positive samples, single infections (SI) with HPV16 were detected in 12.4% (n = 45/364), SI with HPV18 were detected in 1.4%, and infection with at least one of the genotypes included in the high-risk HPV pool was detected in 74.5% of the cases. LA analysis of the samples showed that in addition to HPV genotypes 16 and 18, there was a high prevalence of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico. With respect to the sociodemographic data, we found statistically significant differences in the number of pregnancies, the use of hormonal contraceptives and tobacco intake.ConclusionsOur data indicate that there is a high prevalence of HPV genotypes which are not covered by the vaccines currently available in Mexico; therefore, it is necessary to include HPVs 59, 66, 51, 39 and 56 in the design of future vaccines to reduce the risk of CC development. It is also essential to emphasize that the use of hormonal contraceptives and tobacco smoking are risk factors for CC development in addition to the presence of HPV.

Prevalence of vaginal HPV infection among adolescent and early adult girls in Jos, North-Central Nigeria

Abstract Purpose Knowledge of the prevalence of HPV infection among adolescent and early adult girls is essential to determining the best age for the introduction of HPV vaccine, monitoring vaccine efficacy, and giving insight into determinants of persistent high-risk HPV infection, a necessary cause of cervical cancer. Yet, there have been limited studies of HPV infection among adolescent and early adult girls in low-and-middle-income countries. Methods In this cross-sectional study, we randomly selected 205 girls, aged 9–20 years, from 10 schools in central Nigeria. We obtained informed consent and assent, collected data, and trained participants to self-collect vaginal samples using swab stick. We genotyped HPV using SPF10-DEIA/LiPA25 and analyzed data using Stata 14®. Results The mean (SD) age of the girls was 14.9 (2.3) years. We found HPV in 13.2% of vaginal swabs. The earliest age at which anyHPV and hrHPV infections were detected was 10 and 12 years respectively. The prevalence of any HPV peaked at 16 and 17 years, hrHPV at 16 years, lrHPV at 17 and 18 years and multiple hrHPV 18 years of age. The prevalence of hrHPV infection was 1.5% among the 9–12 years age group, 2.9% among 13–16 years and 3.4% among 17–20 years old. The commonest hrHPV types detected were 52 (3.9%), 18 (1.5%) and 51 (2.4%). The most common lrHPV types was 6 (2.9%). Conclusion The prevalence of HPV infection in these urbanized young girls in Nigeria is high and commences after 9 years of age. HPV vaccination in this population should start at 9 years of age or younger to prevent the establishment of persistent HPV infection.

Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization

Persistent infection with high-risk Human papillomavirus (HPV), specifically HPV-16, is the leading cause of cervical cancer. Although preventative vaccines have shown significant efficacy in preventing HPV infection, cervical cancer is a significant public health issue that affects millions of women worldwide. Modern therapeutic approaches, such as peptide vaccines, could be promising and have potential for the treatment of the HPV-infected population. A HPV16-E7 multi-epitopic vaccine (MEVE7) was designed to comprise potent CD4 + and CD8 + T cell epitopes and optimally expressed in a prokaryotic expression system. Polyclonal antibodies were generated, and their reactivity with immunizing antigen and native protein in E7 expressing cells (TC-1) was assessed by ELISA and immunofluorescent staining, respectively. The efficacy of the vaccine was assessed in a therapeutic animal model of HPV-induced cancer. Our study revealed that the final construct was successfully expressed in E. coli BL21 (DE3)-gold within 4 h of induction as inclusion bodies. Among the tested solubilization buffers, the buffer with a pH of 12 and containing 2 M urea showed the highest solubilization effect. Polyclonal antibodies directed against the E7 multi-epitope vaccine were able to react strongly with the immunizing antigen and E7-bearing cells (TC-1). Immunization of TC-1 tumor-bearing mice with HPV16-E7, markedly delayed tumor growth and propagation. The poly-epitope vaccine for HPV16-E7, as expressed and purified in this research, is highly immunogenic and capable of triggering E7-specific antibodies, making it a potential therapeutic HPV vaccine. Further research is needed to optimize the vaccination schedule and assess the E7-specific immune cell profile.

Neisseria macacae bacteremia: report of two cases with a literature review

Abstract Background Neisseria macacae was discovered in the oral cavity of monkeys in 1983. In humans, it has been isolated from the upper respiratory tract of neutropenic patients. However, only two cases of N. macacae bacteremia have been reported in a 65-year-old man with infective endocarditis and a 5-month-old child with fever and petechiae. There are no reports of infections in cancer patients. Here, we present two cases of N. macacae bacteremia in cancer patients. Case presentation In the first case, a 42-year-old woman who underwent ovarian cancer surgery presented with duodenal invasion associated with multiple lymph node metastasis. N. macacae was isolated from her blood culture and identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). In the second case, a 69-year-old woman with a long-standing history of esophagogastric junction cancer presented with fever. She had stage IVB cancer with lung, bone, and multiple lymph node metastasis. The last chemotherapy was administered 5 weeks before N. macacae was detected using MALDI-TOF MS and nitrate test negative. In both cases, transthoracic echography showed no vegetation. Antibiotics were administered for 14 and 13 days in the first and second cases, respectively. In both cases, fever alleviated on day 4 of antibiotic administration. Both patients were discharged after their conditions improved. Conclusions This, to our knowledge, is the first report of N. macacae bacteremia in cancer patients. Both patients, mucosal damage was observed in the upper gastrointestinal tract. Therefore, exclusion diagnosis suggested that bacteremia invasion was caused by mucosal rupture in both cases. Both cases responded well to treatment with β-lactam antibiotics and improved after 2 weeks. Modifying the treatment based on the source of the infection may shorten the treatment period. Therefore, further research on N. macacae bacteremia is necessary. Immunocompromised patients such as those with cancer are susceptible to mucosal damage by unusual bacterial species such as N. macacae despite not having contact with monkeys.

Impact of HPV-16/18 AS04-adjuvanted vaccine on preventing subsequent infection and disease after excision treatment: post-hoc analysis from a randomized controlled trial

Abstract Background It is widely acknowledged that HPV prophylactic vaccine could prevent new infections and their associated lesions among women who are predominantly HPV-naive at vaccination. Yet there still remains uncertainty about whether HPV vaccination could benefit to individuals who have undergone surgery for cervical disease. Methods This post-hoc analysis intends to focus on intent-to-treat participants who underwent excision treatment at baseline and the follow-up period in a phase II/III, double-blind, randomized trial ( ClinicalTrials.gov , number NCT00779766 ) conducted in Jiangsu province, China. We evaluate the impact of HPV vaccination on preventing women from subsequent infection and cervical lesions (LSIL+ and CIN2+) after excision treatment. Results One hundred sixty-eight (vaccine, n  = 87; placebo, n  = 81) performed excisional treatment in this clinical trial. We observed a significant effect of vaccination on acquiring 14 high-risk HPV (HR-HPV) infection after treatment (vaccine efficacy: 27.0%; 95% CI 4.9, 44.0%). The vaccine efficacy against new infections after treatment for 14 HR-HPV infection was estimated as 32.0% (95%CI 1.8, 52.8%), and was 41.2% (95%CI -162.7, 86.8%) for HPV16/18 infection. The accumulative clearance rates of the vaccine group and placebo group were 88.9 and 81.6% for HPV16/18 infection ( P  = 0.345), 63.4, 48.7% for 14 HR-HPV infection ( P  = 0.062), respectively. No significant difference was observed on the persistent rate of HPV16/18, 14 HR-HPV infection and occurrence rate of LSIL+ between the two groups. Conclusions No significant evidence from this study showed that HPV-16/18 AS04-adjuvanted vaccine could lead to viral faster clearance or have any effect on the rates of persistent infection among women who had excision treatment. However, the vaccine may still benefit post-treatment women with “primary prophylactic” effect. Further research is required in clarifying the effect of using the prophylactic HPV vaccine as therapeutic agents. Trial registration ClinicalTrials.gov identifier : NCT00779766 . Date and status of trial registration: October 24, 2008. Completed; Has Results.

Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort

Abstract Background In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. Methods The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n  = 78), women with low-grade squamous intraepithelial lesions (LSIL, n  = 51), women with high-grade squamous intraepithelial lesions (HSIL, n  = 23), women with invasive cervical cancer (Cancer, n  = 9) and healthy women without HPV infection (Normal, n  = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3 – 4) using Illumina MiSeq. Results HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus , Gardnerella and Atopobium . Accordingly, HPV infection increased the relative abundance of Prevotella , Bacillus , Anaerococcus , Sneathia , Megasphaera , Streptococcus and Anaerococcus . The increased proportions of Bacillus , Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera . The most abundant bacterium in the LSIL group was Prevotella amnii . However, Prevotella timonensis , Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus , Sneathia , Acidovorax , Oceanobacillus profundus , Fusobacterium , Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis . Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. Conclusions This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

Self-collected versus clinician-collected cervical samples for the detection of HPV infections by 14-type DNA and 7-type mRNA tests

Abstract Background HPV self-sampling has been widely supported by the scientific community following a strong body of literature on the subject. Self-sampling is important in cervical cancer screening as it has been shown to improve participation. It is well documented that HPV-testing has proven superior to cytology with regards to sensitivity in detection of CIN and cancer. The value of self-collected samples is reliant on the quality of the molecular testing performed, as well as the patients’ preference in sampling procedure and compliance to follow up on positive test results. Due to the incompatibility of self-samples and cytology, triage of HPV-DNA positives by testing for molecular biomarkers is highly warranted. Methods Our objective was to compare the detection rate of genital Human Papillomavirus (HPV) infection in self- and clinician-collected samples by a 14-type HPV-DNA test and a 7-type mRNA E6/E7 test. Results Five hundred five women were recruited. Each study participant had two sample collection procedures performed upon the same visit, alternating order in execution of the self-collection or the clinician-taken procedure first or second, 1010 samples in total. HPV-DNA prevalence was 22.8% in self-collected versus 19.2% in clinician-collected samples (P = 0.19). Overexpression of mRNA E6/E7 from 7 HPV types was 7.1 and 6.3%, respectively (P = 0.71). The difference between HPV-DNA and HPV-mRNA positivity rates were statistically significant in both self-collected (22.8% versus 7.1%, P &lt; 0.001) and clinician-collected samples (19.2% versus 6.3%, P &lt; 0.001). Overall agreement between the two collection methods was fair, with a concordance rate of 78.2% (390/505), k = 0.34 (95% CI: 0.25–0.44), P &lt; 0.001, for the HPV-DNA test and 92.5% (467/505), k = 0.40 (95% CI, 0.25–0.56), P &lt; 0.001, for the mRNA test, respectively. 96.8% of the participants reported they felt confident carrying out the self-collection themselves, and 88.8% reported no discomfort at all performing the procedure. Conclusions This comparative study of two sampling methods reports fair agreement of HPV positivity rates between the self-collected and clinician-collected specimens using Abbott hrHPV and PreTect HPV-Proofer’7 tests. Only one third of HPV-DNA positive women had overexpression of mRNA E6/E7. Trial registration ISRCTN77337300.

Co-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2–3 among HPV16 positive female: a large population-based study

Abstract Background Evidence suggested that vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of high risk HPV (hr-HPV). Methods From January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received hr-HPV genotyping for cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18, and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly, and cervical tissues were taken for pathology examination to make clear the presence or absence of other cervical lesions. Results Among 310,545 female, 6067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases, and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the detection of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection ( p  &lt; 0.0001). Co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42–2.31). Co-infection with TV increased the risk of CIN 2–3 among female infected with HPV 16 (OR 1.71, 95% CI: 1.16–2.53). Conclusions Co-infection of TV and HPV 16 is a significant factor for the detection of cervical lesions.

Burden of HPV related anogenital diseases in young women in Germany – an analysis of German statutory health insurance claims data from 2012 to 2017

Abstract Background Most individuals are infected with human papillomavirus (HPV) at least once in their lifetime. Infections with low-risk types can cause genital warts, whereas high-risk types can cause malignant tumors. The aim of this study was to determine the burden of anogenital diseases potentially related to HPV in young women based on German statutory health insurance claims data. Methods We conducted a retrospective claims data analysis using the “Institute for Applied Health Research Berlin” (InGef) Research Database, containing claims data from approximately 4 million individuals. In the period from 2012 to 2017 all women born in1989–1992, who were continuously insured between the age of 23–25 years were identified. Using ICD-10-GM codes (verified diagnosis in the outpatient sector or primary or secondary diagnosis in the inpatient sector) the administrative prevalence (95% confidence interval) of genital warts (A63.0), anogenital diseases grade I (K62.8, N87.0, N89.0, N90.0), grade II (N87.1, N89.1, N90.1) and grade III (D01.3, D06.-, D06.0, D07.1, D07.2, N87.2, N89.2, N90.2) was calculated (women with diagnosis divided by all women). Results From 2012 to 2017, a total of 15,358 (birth cohort 1989), 16,027 (birth cohort 1990), 14,748 (birth cohort 1991) and 14,862 (birth cohort 1992) women at the age of 23–25 were identified. A decrease of the administrative prevalence was observed in genital warts (1.30% (1.12–1.49) birth cohort 1989 vs. 0.94% (0.79–1.10) birth cohort 1992) and anogenital diseases grade III (1.09% (0.93–1.26) birth cohort 1989 vs. 0.71% (0.58–0.86) birth cohort 1992). In anogenital diseases grade III, this trend was especially observed for severe cervical dysplasia (N87.2) (0.91% (0.76–1.07) birth cohort 1989 vs. 0.60% (0.48–0.74) birth cohort 1992). In contrast, anogenital diseases grade I (1.41% (1.23–1.61) birth cohort 1989 vs. 1.31% (1.14–1.51) birth cohort 1992) and grade II (0.61% (0.49–0.75) birth cohort 1989 vs. 0.52% (0.42–0.65) birth cohort 1992) remained stable. Conclusions A decrease of the burden of anogenital disease potentially related to HPV was observed in the younger birth cohorts. This was observed especially for genital warts and anogenital diseases grade III. Further research to investigate this trend for the upcoming years in light of varying HPV vaccination coverage for newer birth cohorts is necessary.

Triaging HPV-positive, cytology-negative cervical cancer screening results with extended HPV genotyping and p16INK4a immunostaining in China

Abstract Background Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women. Methods A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + . Results A total of 2731 HPCN women aged 30–64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; ‘HPV16+ or HPV33/58/31/35+&amp;p16+’; ‘HPV16/33+ or HPV58/31/35+&amp;p16+’; HPV16/18/31/33/45/52/58 + &amp; p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the ‘HPV16/33+’ strategy: p16+; ‘HPV16+ or HPV33/58/31/35 + &amp;p16+’; HPV16/18/31/33/45/52/58 + &amp;p16 + . Conclusions Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.

Prevalence of sexually transmitted infections among cervical cancer suspected women at University of Gondar Comprehensive Specialized Hospital, North-west Ethiopia

Abstract Background Sexually transmitted infections (STIs) such as Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Syphilis have continued a significant public health problem, especially in areas with substandard infection prevention and control programs. It is known that STIs are largely associated with the increased occurrence of cervical cancer. To date, little is known about the burden of STIs among cervical cancer suspected women in Ethiopia. Objectives To assess the seroprevalence of STIs and associated risk factors among cervical cancer suspected women with special emphasis on HIV, HBV, HCV, and Syphilis. Methods A hospital-based cross-sectional study was conducted among cervical cancer suspected women at the University of Gondar Comprehensive Specialized Hospital from February to April 2017. A pre-tested and structured questionnaire was used to collect data on patients’ characteristics. The patient’s serum or plasma samples were tested for HIV, HBV, HCV, and syphilis using enzyme-linked immunosorbent assay. In all aspects, the standard operational procedure was strictly followed. Data were analyzed using SPSS version 20 software and presented using tables. Statistical associations were measured using bivariate and multivariable logistic regression. A p -value of below 0.05 was considered statistically significant. Result A total of 403 cervical cancer suspected women with the mean age of 42.54 (SD  +  11. 24) years were enrolled in the study. The overall prevalence of STIs was 16.6% (67/403) and the prevalence of HIV, HBV, HCV, and syphilis was 36/403 (8.9%), 10/403 (2.5%), 4/403 (1%), and 29/403 (7.2%) respectively. History of multiple sexual partners (Adjusted OR = 3.02, 95%CI 1.57–5.79, P  = 0.001), alcohol addiction (Adjusted OR = 2.2, 95%CI 1.07–4.5, P  = 0.031), history of STI (Adjusted OR = 3.38; 95% CI: 1.76–6.47, P  = 0.00) and not use of condom (Adjusted OR = 4.99; 95% CI: 1.5–16.16, P  = 0.007) were significantly associated with STIs. Conclusion The prevalence of STIs was generally higher among cervical cancer suspected patients. Health education is encouraged to promote awareness about the prevention of STIs.

Clinical characteristics of single human papillomavirus 53 infection: a retrospective study of 419 cases

Abstract Background Human papillomavirus (HPV) infection is the main cause of cervical cancer. Characteristics of HPV infections, including the HPV genotype and duration of infection, determine a patient’s risk of high-grade lesions. Risk quantification of cervical lesions caused by different HPV genotypes is an important component of evaluation of cervical lesion. Data and evidence are necessary to gain a deeper understanding of the pathogenicity of different HPV genotypes. The present study investigated the clinical characteristics of patients infected with single human papillomavirus (HPV) 53. Methods This retrospective study analyzed the clinical data of patients who underwent cervical colposcopy guided biopsy between October 2015 and January 2021. The clinical outcomes and the follow-up results of the patients with single HPV53 infection were described. Results 82.3% of the initial histological results of all 419 patients with single HPV53 infection showed negative (Neg). The number of patients with cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, vaginal intraepithelial neoplasia (VaIN)1, CIN1 + VaIN1, CIN1 + VaIN2, and CIN2 + VaIN2 was 45, 10, 2, 9, 6, 1, and 1, respectively. Cancer was not detected in any patient. When the cytology was negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL), we observed a significant difference in the distribution of histological results (P &lt; 0.05). 95 patients underwent follow-up with cytology according to the exclusion criteria. No progression of high-grade lesions was observed during the follow-up period of 3–34 months. Conclusions The lesion caused by HPV53 infection progressed slowly. The pathogenicity of a single HPV53 infection was low.

Effectiveness of HPV vaccination in reducing infection among young Brazilian women

Globally, cervical cancer is an increasing public health issue, and vaccination against HPV has proven to be an effective strategy to reduce this neoplasia. The purpose of this study was to assess the effectiveness of the quadrivalent vaccine in reducing the prevalence and incidence of HPV infection in women, aged 18 to 24 years old, in the cities of Ouro Preto and Mariana, Minas Gerais, Brazil. A concurrent cohort study was performed, with an initial follow-up of 12 to 18 months. The selected young women were interviewed and divided into two groups: vaccinated and unvaccinated. Participants underwent a Pap smear and cervical sample collection for HPV detection, genotyping performed by PCR-RFLP, type-specific PCR, and using the PapilloCheck®. The prevalence of HPV infection was analyzed using the compare proportions test. Poisson and Cox multivariate regression models were used to estimate vaccine effectiveness. There was no significant difference in the overall prevalence of HPV infection between vaccinated and unvaccinated groups (23.6% vs. 18.7%; p = 0.364). However, the prevalence of infection by HPV 6/11, 16 and 18 types in vaccinated young women (1.1%) was lower than in unvaccinated ones (7.5%; p = 0.030). Regarding non-vaccine types, a higher prevalence was identified among vaccinated women (22.5% vs. 11.2%; p = 0.018). The overall incidence of HPV infection was 15.75/100 young women/year in non-immunized women compared to 9.12/100 young women/year among those immunized. The effectiveness of the vaccine was 64.0%, regardless of the viral type, and no vaccinated woman was detected with the specific vaccine HPV-type in follow-up. HPV33/45, related to cross-protection, were detected in 12.3% of vaccinated women and 1.2% of unvaccinated ones (p < 0.001) at baseline. These viral types were identified at follow-up in 2.03/100 young women/year of vaccinated participants and 4.24/100 young women/year of unvaccinated ones. The results showed that the quadrivalent HPV vaccine was effective in reducing the prevalence of vaccine-type HPV and the incidence of infection by any HPV type. Public health policies must encourage vaccination to prevent HPV infection. However, surveillance of HPV infection should be continued to assess the prevalence of different genotypes and the impact of the vaccination program.

Efficacy, safety and immunogenicity of a recombinant human papillomavirus bivalent (types 16, 18) vaccine in healthy 18–30-year-old Chinese women: a phase III, double-blind, randomized, controlled trial

Affordable HPV vaccines are needed to accelerate elimination of cervical cancer. We evaluated the efficacy, safety, and immunogenicity of a recombinant bivalent human papillomavirus (HPV) vaccine composed of L1 virus-like particles (VLPs) for HPV 16 and HPV18 (HPV-2), produced in Pichia pastoris, in healthy Chinese women aged 18-30 years. In this phase 3, double-blind, randomised, placebo-controlled trial conducted at 10 centres in China (Nov 2014-Jan 2020), participants were assigned 1:1 to receive three doses of HPV-2 or placebo at months 0, 2, and 6. The primary endpoint was efficacy against histopathology-confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) associated with HPV16/18 through 48 months. Secondary endpoints were safety (adverse events [AEs] within 1 month of any dose; serious AEs throughout follow-up) and immunogenicity (neutralising antibody titres and seroconversion at Month 7 in a predefined subset). Of 12,000 women enrolled, 11,999 received the first dose and 11,281 completed all three doses. Over 48 months, 17 CIN2 + cases occurred: 3 among vaccine recipients (n = 5190) versus 14 among placebo recipients (n = 5167), corresponding to vaccine efficacy of 78.6% (95% CI 23.3-96.1; p = 0.012). No vaccine-related serious AEs occurred. Solicited local AEs were mainly mild pain, reported by 25.9% of vaccinees and 7.9% of placebo recipients. Fever was the most common systemic AE (27.4% vs. 26.4%). In the immunogenicity subset, 99.7% (349/350) and 99.4% (348/350) of vaccinees were seropositive for HPV16 and HPV18 neutralising antibodies, respectively, at Month 7. Three doses of HPV-2 were well tolerated, highly immunogenic, and efficacious against CIN2 + up to 4 years post-vaccination, supporting further evaluation in the adolescent target population for HPV vaccination campaigns. China Drug Trials Registry (CTR20140626; registered Sept 26, 2014; prospective). gov (NCT02733068; registered April 11, 2016; secondary).

Prevalence and age-related trends of high-risk Human Papillomavirus genomes in Ecuadorian women: a comprehensive cross-sectional study

Human Papillomavirus (HPV) is a leading cause of cervical cancer worldwide. Previous studies on HPV prevalence in Ecuador have presented inconsistent findings due to limited sample sizes and regional foci. This study aims to estimate the prevalence and characteristics of HPV infection in Ecuadorian women, identifying high-risk HPV genomes and age-related trends, using data from the Cervical Cancer Screening and Prevention Program. Data were collected from multiple health centers across Ecuador, particularly focusing on the province of Pichincha, utilizing GeneXpert technology and the Xpert Of 16,197 valid tests, 1,776 were HPV-positive, yielding a prevalence of 11.0%. Women aged 30-39 were the most affected demographic, accounting for 39.7% of positive cases. The most common HPV genomes identified were 31/33/35/52/58, constituting 42.3% of HPV-positive women (P3 pooled). The prevalence of multiple HPV genome infections was 13.8%. The study provides a more nuanced understanding of HPV prevalence in Ecuador, indicating that HPV rates are lower than previous national studies but higher than global estimates. The results lay essential groundwork for targeted public health interventions and suggest the need for future research to address methodological limitations.

Epidemiology of human papillomavirus infection of the uterine cervix among women in Adama, Ethiopia: a cross-sectional study

Worldwide, human papillomavirus (HPV) is a common sexually transmitted infection affecting at least 50% of sexually active individuals at some point during their Life. The worldwide prevalence among women is 11.7%, and the highest prevalence is in sub-Saharan Africa (24%). Persistent HPV infection with high-risk genotypes is now a well-established cause of cervical cancer (CC) and it is demonstrated that they are present in 99.7% of CC cases worldwide. The main purpose of the study was to determine the epidemiology of HPV infection of the uterine cervix among women in Adama, Ethiopia. A cross-sectional study was conducted among 383 women in Adama, Ethiopia, from March to June 2023. A systematic sampling technique was employed and data were collected using a pretested, structured questionnaire. The data were entered into Epi-info 7 and analysed using SPSS version 26. Binary logistic regression for bivariate and multivariate analyses with adjusted odds ratios (AORs) and 95% CIs were used to identify factors associated with HPV infection. The level of significance was defined as a p-value < 0.05. The overall prevalence of HPV infection was 26.6%, with high-risk (hr) HPV genotypes. HPV-16 and HPV-18 constituting 22.5% and 5.9%, respectively. "Other HR-HPV" genotypes accounted for 63.7%. Being divorced (AOR = 2.96: 95% CI: 1.18, 7.40), having post-coital bleeding (AOR = 7.97: 95% CI: 2.17, 29.24), having an early sexual debut (AOR = 3.59: 95% CI: 1.69, 7.65), having multiple sexual partners (AOR = 5.25: 95% CI: 1.73, 15.96), having sexually transmitted infections (AOR = 2.36: 95% CI: 1.32,4.20) and being HIV-positive (AOR = 12.37: 95% CI: 4.57, 33.48) were identified as independent factors significantly associated with HR-HPV infection. There was a greater prevalence of HPV infection in the study area than the worldwide prevalence 11.7%. "Other HR-HPV" genotypes were the major oncogenic HR-HPV genotypes identified. Multiple factors were identified as independent factors significantly associated with HR-HPV infection. Awareness creation campaigns and educational programmes about the prevention of HPV infection and associated risk factors need to be implemented in the community.

Cervical conization and high risk - HPV status changes in relation to menopause: a retrospective longitudinal study based on generalized additive mixed models

The relationship between high-risk human papillomavirus (HR-HPV) infection outcomes and cervical lesion recurrence after conization is well documented. However, the temporal dynamics of human papillomavirus (HPV) status post-conization, especially in postmenopausal women, remain unclear. This retrospective cohort study consecutively enrolled 598 patients who underwent conization, all of whom had baseline HR-HPV positivity and histologically confirmed cervical intraepithelial neoplasia (CIN) 2-3. All patients had at least one follow - up HPV test after surgery. Temporal changes in HPV status following conization and their association with menopause were analyzed using Generalized Additive Mixed Models (GAMM). Among the 598 patients, GAMM analysis revealed a significant decrease in HPV positivity risk over time. Adjusting for confounders, the overall risk of HPV positivity decreased by 59% every 4 months within the first 24 months post-conization (OR: 0.41, 95% CI: 0.35-0.47). After 24 months, the risk continued to decline by 7% every 4 months (OR: 0.93, 95% CI: 0.81-1.06). Menopause status significantly influenced these temporal changes; postmenopausal patients had a 45% increased risk of HPV positivity every 4 months after conization compared to premenopausal patients (OR: 1.45, 95% CI: 1.13-1.85), particularly within the first 24 months (p = 0.0032). In patients undergoing conization, longitudinal HPV infection status changes were independently associated with menopause. The risk of HPV positivity decreased significantly in the first 24 months post-surgery, with a more pronounced decline in premenopausal patients, informing HPV testing strategies post-conization.

Comparative analysis of preoperative and postoperative HPV infection dynamics in patients with cervical intraepithelial neoplasia and cervical cancer: implications for screening and management

Human papillomavirus (HPV) transmission poses significant health risks, particularly in women. This study aims to detail the prevalence and characteristics of HPV infections both before and after surgical treatment in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer. We recruited 370 patients diagnosed with CIN or cervical cancer. The study first assessed the overall prevalence of preoperative HPV infections, analyzing variations across different age groups and histological diagnoses. We then investigated the relationships between postoperative HPV positivity rates and various factors including age, histological diagnoses, HPV genotypes, and the presence of multiple HPV infections. A comparative analysis was also conducted to observe the dynamics of HPV infections before and after cervical operations. An overall HPV positivity rate of 97.0% was observed in patients diagnosed with CIN or cervical cancer, with HPV16, HPV52, HPV58, HPV33, HPV51, and HPV18 being the most prevalent genotypes. The distribution of HPV infection varied significantly by age and histological diagnosis. Notably, the prevalence of HPV16 showed significant differences across age and histological diagnoses groups. Among the 282 patients who underwent surgical treatment, 40.1% remained HPV positive postoperatively, with those aged ≥ 60 years and those with multiple HPV infections showing higher rates of postoperative HPV positivity. The findings confirm the strong association between high-risk HPV infection and the development of CIN and cervical cancer. They also highlight the need for tailored approaches in the postoperative management of HPV to prevent recurrence, offering new insights for improving screening and treatment strategies.

Genital mycoplasma infections: a hidden factor in cervical cancer progression? A systematic review and meta-analysis

Exploring the role of the microbiome, specifically genital mycoplasmas, in cervical cancer (CC) offers insights into tumorigenesis, potential therapeutic targets and personalized treatment strategies. Although mycoplasmas are generally identified as commensals, their contributions to gynecological cancers, mainly CC, is increasingly recognized. This study investigates the association between CC and genital mycoplasma infections, highlighting the interactions with human papillomavirus (HPV) and their impact on cellular and immune mechanisms. We conducted a systematic review and meta-analysis of databases through June 2024. Association strength was determined using pooled odds ratios (ORs) with 95% confidence intervals (CIs). Six case-control studies involving 319 cervical cancer patients and 447 controls were included. Pooled results showed that genital mycoplasmas were associated with a significantly increased risk of CC (OR = 1.64; 95% CI 1.25-2.14). The species-specific analysis demonstrated that Ureaplasma urealyticum was linked with a high risk of CC (OR = 1.81, 95% CI 1.31-2.51), while no significant association was seen for Ureaplasma parvum. HPV-positive subjects co-infected with genital mycoplasmas had a markedly increased risk of CC (OR = 3.13, 95% CI 2.04-4.79), highlighting potential synergistic effects in tumor progression. Mycoplasmas, particularly U. urealyticum, constitute co-factors in the development of CC, likely by influencing HPV persistence and immune evasion. Systemic screening coupled with targeted treatment of genital mycoplasmas in high-risk populations is thus warranted for CC prevention.

A scoping review of human papillomavirus related data system in China

Human papillomavirus (HPV) is a prevalent sexually transmitted infection associated with various diseases, including genital warts, recurrent respiratory papillomatosis (RRP), and multiple pre-cancerous diseases and cancers. HPV causes over 90% of cervical cancer cases, the sixth most common cancer among women in China. To support the national plan for accelerating cervical cancer elimination through enhanced HPV vaccination and screening rates, China requires reliable data systems to monitor and evaluate progress effectively. We conducted a scoping review of literature from PubMed and the China National Knowledge Infrastructure databases, supplemented by government documents and news articles from the Internet, spanning April 2012 and July 2023. Our objective was to identify and summarize databases and data systems used for HPV-related real-world evidence generation in China. The identified data systems cover four primary domains: HPV vaccination, HPV screening, HPV-related cervical and non-cervical diseases, and sexual and lifestyle behaviors. Our review identified a total of 140 articles and 26 databases and data systems. These databases and data systems were categorized into the following reporting areas: HPV vaccination (n = 2), HPV screening (n = 2), HPV-related cervical and non-cervical diseases (n = 21), and sexual and lifestyle behaviors (n = 1). The Immunization Program Information Management System and the regional health care information platform in Ningbo provide HPV vaccination data, while KingMed Diagnostics and the "Two Cancers" Screening Platform track HPV screening at national level. Twenty-one systems were identified for tracking HPV-related cervical and non-cervical diseases, including head and neck cancers, penile lesions, and genital warts; however, no systems were found for anal, vulvar, or vaginal cancers, or RRP. One database, the National Human Immunodeficiency Viruses Epidemiology Database, included information on sexual and lifestyle behaviors. Pilot cities, including Yinzhou, Chengdu, Suzhou, and Lecheng, have implemented population-level data systems capable of identifying information on HPV vaccination, HPV screening, and HPV-related diseases. China has made significant progress in addressing HPV-related diseases and prevention, but more integrated and comprehensive data systems are needed to effectively support research, improve interventions, and achieve national and global goals in HPV prevention and cervical cancer elimination.

HPV genotype distribution and cervical lesions in Chongqing: a comprehensive analysis of 229,770 females (2015‒2023)

Cervical cancer ranks fourth among cancers in women globally, with over 300,000 deaths annually worldwide. Persistent high-risk HPV (HR-HPV) infection is the main cause of cervical cancer. The World Health Organization (WHO) recommends human papillomavirus (HPV) DNA testing for cervical cancer screening. This study analyses the distribution of HPV genotypes and further investigates their association with the severity of cervical lesions, aiming to develop prevention and screening strategies for cervical cancer. A retrospective study was conducted on 229,770 females who underwent HPV DNA testing at The First Affiliated Hospital of Chongqing Medical University between January 2015 and December 2023 to assess the epidemiological distribution of HPV genotypes. In addition, HPV genotypes were further analysed in cervical samples from 749 patients in 2023 who were screened for HPV DNA and had available histological diagnoses. HPV genotyping was performed using capillary electrophoresis analysis. The overall HPV prevalence was 21.41% among 229,770 patients over the past nine years. Among hr-HPV types, the five most common genotypes were HPV52 (4.55%), HPV16 (3.44%), HPV58 (2.94%), HPV56 (1.33%), and HPV39 (1.32%). Single HPV infection (16.89%) was more common than multiple infections. HPV prevalence exhibited a bimodal distribution, peaking in the under-30 and over-60 age groups. Among 749 HPV-positive patients, the cervical cancer group had the highest median age of 55(interquartile range, 48‒65) years. HPV16 showed the highest prevalence across the different degrees of cervical lesions, followed by HPV52 and HPV58. HR-HPV was found in nearly all cervical cancer cases, with a prevalence of 88.43%, 98.55%, and 97.39% in the low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and cervical cancer groups, respectively. The distribution of HPV genotypes varies by year and age group. HPV16, HPV18, HPV52, and HPV58 are the predominant genotypes detected in high-grade cervical lesions and cervical cancer groups. Given the high prevalence in these lesions, vaccines incorporating HPV52 and HPV58 may offer enhanced protection. Based on local epidemiological data, adaptable vaccination programs and effective screening are essential for preventing and reducing the risk of cervical cancer.

Associations of Atopobium, Garderella, Megasphaera, Prevotella, Sneathia, and Streptococcus with human papillomavirus infection, cervical intraepithelial neoplasia, and cancer: a systematic review and meta-analysis

Abstract Background Lactobacillus spp. depleted and high diversity of vaginal microbiota is closely related to human papillomavirus infection and cervical cancer. However, the role of other microbial communities in human papillomavirus infection and cervical cancer is still unclear. Objective This study aims to systematically review the existing literature and perform a meta-analysis to statistically evaluate the relationship between vaginal microbiota, human papillomavirus infection, cervical intraepithelial neoplasia, and cervical cancer at the genus level. Methods A comprehensive search of PubMed, Web of Science, and Embase databases was conducted to identify relevant studies. We synthesized data on the relative abundance of specific bacterial species associated with human papillomavirus status and cervical lesions. SPSS 25.0 was used to compare relative abundance among multiple groups. Results The meta-analysis included 17 observational studies published between 2019 and 2023, involving 2014 participants from Asia, North America, and Africa. We found that specific vaginal microorganisms, such as Gardnerella, Prevotella, Sneathia, and Streptococcus, showed increased relative abundance with the severity of cervical lesions in human papillomavirus-negative, human papillomavirus-positive, cervical intraepithelial neoplasia, and cervical cancer patients. However, no statistically significant differences were found in that regard. Notably, Prevotella was significantly more abundant in cervical cancer patients compared to human papillomavirus-negative individuals. Sneathia was also found to be more abundant in cervical intraepithelial neoplasia and cervical cancer patients. Conclusions The specific vaginal microbial species are associated with human papillomavirus infection status and the severity of cervical lesions that may have significant implications for the prevention and treatment strategies of cervical cancer.

HPV-associated squamous cell carcinoma and adenocarcinoma in distinct cervical sites: a case report

The synchronous occurrence of adenocarcinoma and squamous cell carcinoma in distinct cervical regions is exceptionally rare. This report highlights a case of HPV-associated adenocarcinoma and squamous cell carcinoma at distinct sites in a patient with primary stage IA1 cervical cancer. A 54-year-old female tested HPV type 18 positive in a routine physical exam. Cervical Liquid - based Cytology Test (LCT) showed Atypical Squamous Cells of Undetermined Significance (ASCUS). Colposcopy-directed biopsies revealed moderately differentiated squamous cell carcinoma at multiple sites (3, 6, 9, 12 o'clock positions and the ECC), with a clinical diagnosis of stage IA1. Preoperative abdominal MRI (including contrast enhancement) showed no lymph node enlargement, and urinary CT urography was normal. Squamous cell carcinoma antigen levels were within the normal range.

Human papillomavirus (HPV) infection and liquid-based cytologic tests among cervical screening participants in Shannan City, Tibet, China, during 2021–2022

Cervical cancer is the most common malignant tumor of the reproductive tract in women and poses a serious threat to their health. Cervical cancer screening is primarily conducted through the detection of HPV or cytological examination. In this study, we analyzed the prevalence, genotyping of HPV, and cervical cytology among women in Shannan city, Tibet, China, between 2021 and 2022, to guide the prevention of cervical cancer among local women. This is the first large-scale cervical cytology screening study conducted in the southern region of the province. Between January 2021 and December 2022, 15,493 women participated in HPV genotype testing, and 16,775 women underwent ThinPrep cytologic tests. HPV prevalence and genotype distribution were analyzed for the entire population. Furthermore, the samples were stratified by age group and altitude to analyze the HPV infection rate and distribution of cervical cytological abnormalities. The prevalence of HPV in Shannan city was 7.91%, with HPV16 and HPV18 affecting 1.21%. Single infections (95.92%) were more common than multiple infections (4.08%). The overall HPV infection rate peaked in the cohort < 25 years of age (13.25%). Furthermore, HPV infection rates and cervical cell abnormalities varied according to the administrative division in Shannan city, and this difference was attributed to various altitudes. Among HPV carriers, the infection rate peaks in women aged 25 years, after which it declined annually, and the probability of coinfection is relatively low. Additionally, we found that high-altitude areas exhibited elevated HPV prevalence but fewer cervical abnormalities, suggesting complex environmental, genetic, and cultural influences on infection and disease progression. Based on these data, effective recommendations can be made for cervical cancer screening and HPV prevention in local communities.

Overcoming HPV vaccine hesitancy: insights from a successful school-based vaccination campaign in the Saa health district of Cameroon

Vaccination against human papillomavirus (HPV) represents a critical strategy in the global effort to eradicate cervical cancer. Nonetheless, the uptake of HPV vaccination in Cameroon has been slow, resulting in vaccine wastage during a period of constrained global supply. In the Saa health district, factors such as concerns about infertility, fears of COVID-19 infection, and restrictions on HPV awareness initiatives in Catholic churches and schools have been identified as contributors to vaccine hesitancy. This report outlines the observations from a successful impromptu HPV vaccination campaign conducted in the context of this hesitancy within the Saa health district. The campaign took place from the 9th to 25th of May 2023 and targeted 853 adolescents aged 9-13 years. A single-dose schedule with Gardasil was used mainly through the school strategy. Community health workers, teachers and priests participated in sensitization activities via door-to-door sensitization for parents, sensitization in schools for students and in churches for faithfuls respectively. Health facilities vaccinated schools in their catchment area. Vaccination data were recorded in routine vaccination registers. A total of 1321 adolescents (154%) were vaccinated, 48.9% (n = 646) of whom were boys. Thirty-four primary and two secondary schools participated in the campaign. Health workers, teachers and Catholic priests all participated in sensitization activities. No backlash was reported from parents after vaccination. The successful execution of the campaign can be attributed to the active involvement of key stakeholders within the health district. Continuous advocacy for HPV vaccination, even in a climate of vaccine hesitancy, plays a significant role in positively altering perceptions. Recognizing stakeholders and their influence is essential for tailoring strategies aimed at enhancing HPV vaccine uptake.

Prevalence and risk factors of high-risk HPV and cervical abnormalities in HIV-positive women in Bali, Indonesia

Women living with Human Immunodeficiency Virus (HIV) are at higher risk of cervical cancer, particularly in regions like Indonesia where cervical cancer screening programs are limited. Bali has seen a rise in both HIV and cervical cancer cases, prompting the need for targeted interventions. This study investigates the prevalence of cervical cytological abnormalities and associated risk factors among women with HIV in Bali, focusing on their relationship with high-risk Human Papillomavirus (HR-HPV) types. A cross-sectional study was conducted from July to December 2023, recruiting 245 women from HIV outpatient clinics in Bali. Demographic and clinical data were collected via interviews and physical examinations, including cervical swabs and blood samples. HPV genotyping was performed using ThinPrep cytology followed by a two-stage PCR process. The first stage utilized universal primers (MY09/11) for HPV detection, while the second stage employed type-specific primers to identify high-risk strains, (16,18,31,33,35,39,45,51,52,56,58,59,66 and 68. Blood samples were analyzed to determine CD4 and CD8 T-cell counts. Of 239 participants, 26 (10.87%) had abnormal cytology (6 cases (2.5%) of atypical squamous cells with high risk (ASC-H), 9 cases (3.8%) of atypical squamous cells of undetermined significance (ASC-US), 4 cases (1.7%) of high-grade squamous intraepithelial lesions (H-SIL), and 7 cases (2.9%) of low-grade squamous intraepithelial lesions (L-SIL)). Furthermore, 58 participants (24%) were tested positive for HPV DNA, with HPV type 18 being the most prevalent (28% in all HPV-positive samples). HPV-positive women had a seven-fold higher risk of abnormal cytology (PR = 7.022, 95% CI = 3.223-15.295). Multivariate analysis revealed HPV 18 as an independent risk factor (ExpB = 9.029, p = 0.007) and a history of pap smear screening reduced HR-HPV risk (ExpB = 0.358, p = 0.013). This study highlights that 10.87% of HIV-positive women in Bali had abnormal cytology, with HPV 18 significantly linked to higher risk. A history of pap smear screening reduced HR-HPV risk. These findings underscore the need for robust cervical cancer screening and HPV vaccination, particularly for younger women, to improve health outcomes in Indonesia.

Prevalence of non-vaccine high-risk HPV cervical infections in vaccinated women: a systematic review and meta-analysis

Human Papillomavirus (HPV) is the most common sexually transmitted lower genital tract infection worldwide and the main etiological factor of cervical cancer (CC). Since 2006, vaccines have been implemented to reduce CC-related morbidity and mortality. This systematic review and meta-analysis aimed to evaluate the prevalence of cervical infections by non-vaccine high-risk HPV (HR-HPV) types in women vaccinated against types 16 and 18. This systematic review and meta-analysis used independent electronic databases - Lilacs, WHO, BDENF, State Department of Health SP, Health Information Locator, IRIS, Coleciona Sistema Único de Saúde, BINACIS, IBECS, CUMED and SciELO, on July 14, 2023. Observational studies that evaluated vaccinated and unvaccinated women against HR-HPV and the prevalence of cervical infection by types of HR-HPV were included. Intervention effects were expressed as prevalence ratios (PR). Forest plots were used to visualize vaccination effects. The study protocol was previously registered in PROSPERO, under code CRD42023440610. Of the 7,051 studies, 31 met the analysis criteria. A total of 59,035 women were eligible for this systematic review. The results showed a high prevalence of non-vaccine HR-HPV types, regardless of vaccination status. For HPV 31/33/45 (PR = 0.60 [0.40-0.91]), HPV31 (PR = 0.47 [0.31-0.72]), and HPV 45 (PR = 0.38 [0.22-0.69]), a positive random effect was found. The prevalence of non-vaccine HR-HPV cervical infection was high in women, regardless of vaccination status. For HPV types 31 and 45 and 31/33/45, the prevalence was lower in vaccinated women, suggesting a cross-protective effect of vaccines for these viral types.

Validity of Mehrviru® and Sacace® in molecular detection of HPV: a latent class analysis

Valid diagnostic tests for human papillomavirus (HPV) detection are crucial to identify individuals at high risk of cervical cancer. We assessed and compared the validity of Mehrviru HPV genotyping and Sacace (HPV Genotypes 14 Real-TM Quant) for molecular detection of 14 high-risk human papillomaviruses. We used three HPV test results to identify HPV-positive individuals (14 high-risk genotypes) in a specialist gynecology clinic. The HPV test results were collected using Mehrviru We examined 117 women at high risk of HPV infection. The mean age (SD) was 37.2 (9.1). According to LCA, 28.6% of participants had an HPV infection. The sensitivity and specificity (95% CI) of the Mehrviru were 90.8% (73.7-97.2%) and 90.9% (82.1-95.6%), and corresponding figures for Sacace were 92.0% (72.3-98.1%) and 97.4% (90.2-99.3%). The kappa index between the Mehrviru and Sacace kits was 69.7% (55.6-83.9%). The area under the ROC curve for Mehrviru and Sacace test were 91.4% (85.7-97.1%) and 94.4% (89.3-99.5%). There is an excellent agreement between Mehrviru and Sacace test results, and the diagnostic accuracy indices were similar.

Prevalence of vaginal and cervical HPV infection among 35-year age cohort ever-married women in Kalutara district of Sri Lanka and the validity of vaginal HPV/DNA specimen as a cervical cancer screening tool: a cross-sectional study

Cervical cancer is the 2nd most common female cancer among Sri Lankan females and is almost associated with sexually transmitted cervicovaginal human papillomavirus (HPV) infection. The study objectives were to determine the prevalence of vaginal and cervical HPV infection among 35year old ever-married women and assess the validity of primary healthcare provider-collected vaginal HPV/DNA specimens as a cervical cancer screening tool to improve the coverage of the programme. A descriptive cross-sectional study was carried out from the 1st of September 2018 to the 31st of January 2019. Ever-married women 35 years of age in Kalutara district were the study population. Two women from each Public Health Midwife area (n = 413) were selected randomly from the relevant area eligible families register/s. HPV/DNA cervical specimen and vaginal specimen collection (n = 621) were carried out. Specimens were screened by the Cobas 4800 HPV/DNA automated Polymerase Chain Reaction (PCR) machine. Participants' profiles were recorded by the research assistants using an interviewer-administered questionnaire. The overall prevalence of vaginal and cervical HPV infection was 7.08% (95% CI; 5.2-9.4%) and 6.12% (95% CI; 4.26-8.3%) respectively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and the kappa coefficient of the vaginal HPV/DNA screening method vs. cervical HPV/DNA screening method were 100%, 98.9%, 86.4%, 100%, 99% and 0.92 respectively. Vaginal HPV/DNA specimen screening method can be used as a cervical cancer screening tool due to its high validity. Pilots of the feasibility should be set up before the regional or national rollout of vaginal sampling strategies.

High-risk human papillomavirus diversity among indigenous women of western Botswana with normal cervical cytology and dysplasia

Abstract Background Cervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access. Aim To determine the prevalence of hrHPV genotypes and cervical lesions’ burden in women from the indigenous and marginalized communities of Botswana. Methods This prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68. Results In this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia. Conclusions Our study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs.

Epidemiological study of human papillomavirus infection in 105,679 women in Wuhan, China

Quality assessment of the prevalence and distribution of human papillomavirus (HPV) genotypes could support additional targeted HPV vaccinations. However, the characteristics of HPV infection in Wuhan city are limited in the past decade. We aimed to assess the epidemiology of HPV infection among women and provide a reference for the prevention and treatment of cervical cancer in this region. A retrospective study employing 105,679 women attending Wuhan Medical and Health Center for Women and Children for cervical cancer screening from January 2015 to December 2022 was conducted. The HPV genotype was detected by polymerase chain reaction (PCR) and diversion hybridization. The overall incidence and age-specific type distribution of HPV infection and the relationship between HPV infection and cervical cytology were analyzed. The overall HPV infection rate was 16.87% in Wuhan city, and the prevalence rates of high-risk, low-risk and mixed high- and low-risk HPV infections were 13.64%, 1.77% and 1.46%, respectively. The five most prevalent genotypes were HPV52 (4.24%), HPV58 (2.42%), HPV16 (2.34%), HPV53 (1.87%), and HPV39 (1.66%). The prevalence of HPV in women exhibited a "two-peak" pattern, the peaks of which were observed in the < 21 years group (37.4%) and the 61-65 years group (41.72%). Logistic regression analysis revealed no significant difference in the rate of high-grade lesion positivity between single and multiple high-risk HPV infections. Among patients with a high-grade squamous intraepithelial lesion+ (HSIL+) ThinPrep cytologic test (TCT) diagnosis, HPV58 was the most common type, followed by HPV52, HPV16, HPV39 and HPV53. HPV types 52, 58, 16, 53, and 39 were the most common types in the general female population in Wuhan, and the prevalence of HPV infection varied among different age groups. This study provides a comprehensive overview of the epidemiological characteristics of HPV infection in women, which could support the development of targeted prevention and control strategies for cervical cancer in the region.

Population-based age- and type-specific prevalence of human papillomavirus among non-vaccinated women aged 30 years and above in Germany

Abstract Background A persisting high-risk human papillomavirus (HR-HPV) infection is causal for cervical cancer; however, there is limited population-based data on the prevalence of HPV infections in Germany. We assessed the age and type-specific HPV prevalence, and associated risk factors in HPV unvaccinated women aged 30 and above. Methods The MARZY prospective population-based cohort study was conducted between 2005 and 2012 in Mainz and Mainz-Bingen, Germany. Eligible women were randomly recruited from population registries and invited for cervical cancer screening (n = 5,275). A study swab (liquid-based cytology) was taken and HPV testing was performed with GP5+/6 + polymerase chain reaction (PCR) followed by genotyping. We assessed HPV types as HR-HPV, ‘moderate’ risk and low-risk (LR-HPV). Logistic regression was performed to identify factors associated with HPV infection, stratified by HPV types. Results 2,520 women were screened with a valid PCR result. Overall HPV prevalence was 10.6% (n = 266), with 6.5% HR-HPV positive (n = 165), 1.5% ’moderate’ risk type (n = 38) and 3.3% LR-HPV type (n = 84) positive. 8.9% had a single infection (n = 225) and 1.6% had multiple types (n = 41). The most common HR-HPV types were 16, 56, 52 and 31 and LR-HPV 90 and 42. Of 187 HR-HPV infections detected (among 165 women), 55.1% (n = 103) were with HPV types not covered by available bivalent or quadrivalent HPV vaccines. About 23% (n = 43) were of types not covered by the nonavalent vaccine (HPV 35, 39, 51, 56, 59). The HR and LR-HPV prevalence were highest in the age group 30–34 years (HR 9.8%, ‘moderate’ risk 3.0% and LR 5.6%), decreasing with increasing age. HR-HPV prevalence in women with normal cytology was 5.5%. In women with a high-grade squamous intraepithelial lesion (HSIL), prevalence was 66.7%. Women currently not living with a partner and current smokers had increased chances of an HR-HPV infection. Conclusion The overall population-based HPV prevalence was relatively high. An important share of prevalent HR-HPV infections constituted types not covered by current HPV vaccines. With the advent of HPV screening and younger vaccinated cohorts joining screening, HPV types should be monitored closely, also in older women who were not eligible for HPV vaccination.

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

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. 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. 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. 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.

A designathon to co-create HPV screening and vaccination approaches for mothers and daughters in Nigeria: findings from a community-led participatory event

Abstract Background Oncogenic types of human Papillomavirus (HPV) infection cause substantial morbidity and mortality in Nigeria. Nigeria has low cervical cancer screening and vaccination rates, suggesting the need for community engagement to enhance reach and uptake. We organised a designathon to identify community-led, innovative approaches to promote HPV screening and vaccination for women and girls, respectively, in Nigeria. A designathon is a three-phase participatory process informed by design thinking that includes the preparation phase that includes soliciting innovative ideas from end-users, an intensive collaborative event to co-create intervention components, and follow-up activities. Methods We organised a three-phase designathon for women (30-65yrs) and girls (11-26yrs) in Nigeria. First, we launched a national crowdsourcing open call for ideas on community-driven strategies to support HPV screening among women and vaccination among girls. The open call was promoted widely on social media and at in-person gatherings. All eligible entries were graded by judges and 16 exceptional teams (with 4-6members each). All six geo-political zones of Nigeria were invited to join an in-person event held over three days in Lagos to refine their ideas and present them to a panel of expert judges. The ideas from teams were reviewed and scored based on relevance, feasibility, innovation, potential impact, and mother-daughter team dynamics. We present quantitative data on people who submitted and themes from the textual submissions. Results We received a total of 612 submissions to the open call from mother-daughter dyads. Participants submitted ideas via a website designated for the contest ( n  = 392), in-person ( n  = 99), email ( n  = 31), or via an instant messaging application ( n  = 92). Overall, 470 were eligible for judging after initial screening. The average age of participants for daughters was 19 years and 39 years for mothers. Themes from the top 16 proposals included leveraging local leaders (5/16), faith-based networks (4/16), educational systems (4/16), and other community networks (7/16) to promote awareness of cervical cancer prevention services. After an in-person collaborative event, eight teams were selected to join an innovation training boot camp, for capacity building to implement ideas. Conclusions Innovative strategies are needed to promote HPV screening for mothers and vaccination for girls in Nigeria. Our designathon was able to facilitate Nigerian mother-daughter teams to develop cervical cancer prevention strategies. Implementation research is needed to assess the effectiveness of these strategies.

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

AbstractIn 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.

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

Abstract 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.

An evaluation of the cost of human papilloma virus (HPV) vaccine delivery in Zambia

Abstract Background Human papillomavirus (HPV) is a common sexually transmitted infection and the leading cause of cervical cancer. The HPV vaccine is a safe and effective way to prevent HPV infection. In Zambia, the vaccine is given during Child Health Week to girls aged 14 years who are in and out of school in two doses over two years. The focus of this evaluation was to establish the cost to administer a single dose of the vaccine as well as for full immunisation of two doses. Methods This work was part of a broader study on assessing HPV programme implementation in Zambia. For HPV costing aspect of the study, with a healthcare provider perspective and reference year of 2020, both top-down and micro-costing approaches were used for financial costing, depending on the cost data source, and economic costs were gathered as secondary data from Expanded Programme for Immunisation Costing and Financing Project (EPIC), except human resource costs which were gathered as primary data using existing Ministry of Health salary scales and reported time spent by different health cadres on activities related to HPV vaccination. Data was collected from eight districts in four provinces, mainly using a structured questionnaire, document reviews and key informant interviews with staff at national, provincial, district and health facility levels. Administrative coverage rates were obtained for each district. Results Findings show that schools made up 53.3% of vaccination sites, community outreach sites 30.9% and finally health facilities 15.8%. In terms of coverage for 2020, for the eight districts sampled, schools had the highest coverage at 96.0%. Community outreach sites were at 6.0% of the coverage and health facilities accounted for only 1.0% of the coverage. School based delivery had the lowest economic cost at USD13.2 per dose and USD 28.1 per fully immunised child (FIC). Overall financial costs for school based delivery were US$6.0 per dose and US$12.4 per FIC. Overall economic costs taking all delivery models into account were US$23.0 per dose and US$47.6 per FIC. The main financial cost drivers were microplanning, supplies, service delivery/outreach and vaccine co-financing; while the main economic cost drivers were human resources, building overhead and vehicles. Nurses, environmental health technicians and community-based volunteers spent the most time on HPV related vaccination activities compared to other cadres and represented the greatest human resource costs. Conclusions The financial cost of HPV vaccination in Zambia aligns favourably with similar studies conducted in other countries. However, the economic costs appear significantly higher than those observed in most international studies. This discrepancy underscores the substantial strain placed on healthcare resources by the program, a burden that often remains obscured. While the vaccine costs are currently subsidized through the generous support of Gavi, the Vaccine Alliance, it’s crucial to recognize that these expenses pose a considerable threat to long-term sustainability. Consequently, countries such as Zambia must proactively devise strategies to address this challenge.

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

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

Chlamydia trachomatis enhances HPV persistence through immune modulation

AbstractChlamydia trachomatis (CT) is the most common sexually transmitted infections globally, and CT infection can enhance HPV persistence. Epidemiological analysis has shown that patients with CT/HPV coinfection have a higher risk of developing cervical cancer and exhibit more rapid progression to cervical cancer than patients with HPV infection alone. However, the mechanism has not been fully elucidated. Here, we report that CT infection supports HPV persistence by further suppressing the functions of Langerhans cells (LCs); in particular, CT further activates the PI3K pathway and inhibits the MAPK pathways in LCs, and these pathways are frequently involved in the regulation of immune responses. CT/HPV coinfection also impairs LC functions by reducing the antigen-presenting ability and density of LCs. Moreover, CT/HPV coinfection can alter T-cell subsets, resulting in fewer CD4 + and CD8 + T cells and more infiltrating Tregs. Moreover, CT/HPV coinfection decreases the CD4 + /CD8 + T cell ratio to below 1, coinfection also induces greater T lymphocytes’ apoptosis than HPV infection, thus impairing cell-mediated immunity and accelerating the progress to cervical cancer.

Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples

Abstract Background The human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-miR-195-5p in Pap smear samples from southeast Iranian women. We compared samples that were HPV-positive but showed no abnormality in the cytological examination to samples that were HPV-positive and had severe dysplasia. Methods Pap smear samples were obtained from 60 HPV-positive (HPV-16/18) patients with histologically confirmed severe dysplasia (cervical intra-epithelial neoplasia (CIN 3) or carcinoma in situ) and the normal cytology group. The expression of hsa-miR-194-5p and hsa-miR-195-5p was analyzed by real-time quantitative PCR, using specific stem-loop primers and U6 snRNA as the internal reference gene. Clinicopathological features were associated with miRNA expression levels. Furthermore, functional enrichment analysis was conducted using in silico tools. The Kaplan–Meier survival method was also obtained to discriminate survival-significant candidate miRNAs in CC, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value. Results Compared to HPV-positive cytologically normal Pap smear samples, hsa-miR-194-5p and hsa-miR-195-5p relative expression decreased significantly in HPV-positive patients with a severe dysplasia Pap smear. Kaplan–Meier analysis indicated a significant association between the miR-194 decrease and poor CC survival. In essence, ROC curve analysis showed that miR-194-5p and miR-195-5p could serve as valuable markers for the development of cervix dysplasia in individuals who are positive for high-risk HPVs. Conclusions This study revealed that hsa-miR-194-5p and hsa-miR-195-5p may possess tumor suppressor capabilities in the context of cervical dysplasia progression. However, it remains uncertain whether these microRNAs are implicated in the transition of patients with high dysplasia to cervical cancer. We also showed the potential capability of candidate miRNAs as novel diagnostic biomarkers related to cervical dysplasia progression.

Vaginal pH value can affect the susceptibility to human papillomavirus infection

Abstract Background Cervical cancer is the fourth most common cancer among women, with persistent high-risk human papillomavirus (HPV) infection being responsible for its progression. In healthy, pre-menopausal women, the vaginal pH value is maintained at 3.8–4.5, but various factors can affect it. Previous studies have suggested the relationship between vaginal pH value and HPV infection. In this study, we aimed to explore the relationship between vaginal pH and susceptibility of HPV infection. Methods In our study, we retrospectively collected medical information from women who underwent leukorrhea examination at our hospital. We excluded women with infectious diseases or cancer, those who were pregnant or within 6 months post-delivery, and those without HPV test results within 6 months. The association between percentage of HPV infection and vaginal pH value was analyzed. Furthermore, we prepared HPV pseudovirus (PsVs) by co-transfecting structure plasmids and report plasmids in 293FT cells. In vitro, we changed the pH value of cell culture medium to investigate its influence on HPV PsVs infection. In vivo, we changed mouse’s vaginal pH value to investigate its influence on HPV PsVs infection. Results Our retrospective study included 3115 women aged 20–78, including 2531 women with HPV negative and 584 women with HPV positive. The percentages of both HPV infection and high-risk HPV infection were higher in women with a vaginal pH value ≥5.0 compared to those with a pH value &lt; 5.0. In vitro, HPV PsVs infection rate was higher in cell culture medium of higher pH value, dominantly due to the influence of pH value on the stage of HPV PsVs adhering to cell surface. Neither of the cell surface HPV receptors Syndecan-1 nor integrin α6 was found to be changed obviously in different pH values. In vivo, more HPV PsVs were adhered to the mouse’s vaginal epithelial cells with the increase of the vaginal pH value. Conclusions Our study suggests a possible association between vaginal pH value and HPV infection. The pH value can influence the susceptibility of HPV PsVs infection by affecting the adhering of HPV PsVs to cells in vivo and in vitro. Additionally, the cell surface HPV receptors Syndecan-1 and Integrin α6 do not seem to be affected by pH value, and the specific mechanism needs to be further explored.

A comparative analysis of cycle threshold (Ct) values from Cobas4800 and AmpFire HPV assay for triage of women with positive hrHPV results

Abstract Background To compare the triage performance of HPV viral loads reflected by cycle threshold values (CtV) from two different HPV testing assays: the PCR based Cobas4800 and the isothermal amplification based AmpFire assay. Methods We used the data from a sub-study of The Chinese Multi-Center Screening Trial and analyzed the data of the cases positive in both Cobas4800 and AmpFire assays with recorded CtV. Spearman’s correlation was applied to analyze the association between CtV from AmpFire and Cobas4800 assays, as well as the correlation between CtV and the histological lesion grades. The 50th percentile of CtV was used as the cutoff to construct triage algorithms for HPV-positive cases. McNemar’s test was used to analyze the differences in sensitivity and specificity for detecting CIN2 + and CIN3 + in different triage algorithms. Results Four hundred forty-six HPV positive women who had consistent HPV results from Cobas4800 and AmpFire in terms of the HPV genotype and reported Ct values were included in the analysis. The mean CtV of hrHPV tested by Cobas4800 and AmpFire were linear correlated. Direct association were showed between the severity of cervical lesions and the HPV viral loads reflected by CtV of hrHPV, HPV16, non-16/18 hrHPV and A9 group from both assays. HPV16/18 genotyping combined with low-CtV for non-16/18 hrHPV, especially A9 group, were demonstrated to be satisfactory in the sensitivity and specificity for detecting CIN2 + or CIN3 + . Conclusion Ct value represented a good triage marker in both PCR-based and isothermal amplification HPV detection.

Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions

Abstract Background The aim of this study was to determine the prevalence of high-risk human papillomavirus (HR-HPV) and the correlation between multiple infections and cervical lesions. Methods The current study involved population-based sample of 20,059 women who underwent cervical screening for 15 HR-HPV genotypes with ThinPrep cytologic test (TCT) results. The correlation between multiple HPV genotype infections and cervical lesions was also determined. The odds ratios (ORs) were calculated to assess co-infection patterns for each genotype with 15 other genotypes and the additive statistical interactions were evaluated. Results There was a bimodal pattern among multiple HPV infections, with a peak in the younger group and a second peak in the elderly group. Indeed, most multiple HPV genotypes exhibited a bimodal pattern. The most common HPV type in patients with high-grade squamous intraepithelial lesions (HSILs) was HPV-16, followed by HPV-52, HPV-58, and HPV-33. The most frequent HPV type in patients with cervical cancer was HPV-16, followed by HPV-58 and HPV-33. Women with multiple infections were at a increased risk of low-grade squamous intraepithelial lesions [LSIL] (OR = 2.01; 95% CI 1.38–2.93) and HSIL (OR 2.28; 95% CI 1.36–3.81) when compared to women with single infections. patients with cervical cancer had the higher percentage of multiple HPV infections. Based on the data herein, we suggest that HPV-33 and HPV-58 may also be high-risk HPV types worthy of increased surveillance and follow-up. Conclusion: Our findings suggested that the association between multiple HPV infections and HSIL and LSIL are stronger compared to single HPV infections. There may be some specific combinations that synergistically affected the risk of HSIL and LSIL.

Comparative analysis of SD biosensor standard™ M10 HPV and seegene anyplex™ II HPV HR for detecting high-risk human papillomavirus: a concordance study

Abstract Background Cervical cancer, primarily caused by persistent high-risk human papillomavirus (hrHPV) infections, is a significant health burden, particularly in low-resource settings such as Sarawak, Malaysia. Effective prevention depends on effective vaccination and early hrHPV detection. This study compares the performance of the point-of-care test (POCT) SD Biosensor Standard™ M10 HPV and laboratory-based Seegene Anyplex™ II HPV HR assay, focusing on their ability to detect and genotype hrHPV in self-collected high vaginal swab samples. Methods A total of 151 archived self-sampled high vaginal swabs from the Sarawak Urban and Rural Action for Cervical Cancer Elimination Programme (Program SUARA) were analyzed. hrHPV detection and genotyping were performed using Anyplex, which identifies 14 hrHPV genotypes, and M10, which detects HPV16, HPV18, and other hrHPV categorized into six genogroups. Agreement between the assays was evaluated using Cohen’s Kappa (κ), McNemar’s test, and overall agreement percentages. Statistical significance was determined with p-values, and discordant results were further analyzed for potential diagnostic implications. Results The overall agreement between M10 and Anyplex for hrHPV detection was 92.05% (κ = 0.84, 95% CI 0.75–0.93), indicating almost perfect agreement. M10 demonstrated comparable sensitivity for detecting HPV16, HPV18, and other hrHPV genotypes, achieving 96.91% agreement (κ = 0.89, 95%CI 0.73-1.00) in hrHPV classification when discordant results were excluded. Genogrouping also showed almost perfect agreement (κ = 0.91, 95% CI 0.82–0.98). McNemar’s test indicated no significant difference in hrHPV detection rates (p &gt; 0.05), affirming their comparable performance in detecting clinically significant hrHPV infections. Conclusion The SD Biosensor Standard™ M10 HPV POCT and the Seegene Anyplex™ II HPV HR assay demonstrated almost perfect agreement in hrHPV detection and classification, supporting their complementary roles in cervical cancer prevention. M10’s rapid, field-deployable design makes it suitable for resource-limited settings, while Anyplex provides enhanced genotyping capability in laboratory environments, allowing informed vaccine strategy. Incorporating both assays into cervical cancer prevention programs can improve screening coverage and accessibility, particularly in underserved areas. These findings align with the World Health Organization’s cervical cancer elimination goals, reinforcing the importance of adaptable diagnostic tools in diverse healthcare contexts.

Case report: meningitis as a presenting feature of anti-NMDA receptor encephalitis

Abstract Background Meningitis is a very rare atypical presenting feature of anti-NMDA receptor encephalitis. In our case report, we describe an unusual clinical presentation of anti-NMDA receptor encephalitis with a biphasic pattern of meningitis followed by encephalitis and discuss potential mechanisms underlying this presentation. We aim to widen the differential diagnosis to be considered in a patient presenting with clinical meningitis and pyrexia. Case presentation This is a case of a 33-year old Caucasian woman who initially presented with a lymphocytic meningitis attributed to a viral infection. She subsequently developed fluctuating consciousness, agitation, visual hallucinations, dyskinetic movements, a generalized tonic-clonic seizure, and autonomic instability. Investigations revealed a diagnosis of anti-NMDA receptor encephalitis secondary to a previously unidentified ovarian teratoma. She made an excellent recovery with immunotherapy and removal of the teratoma. Conclusion Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative pathogen and there is rapid development of an encephalitic phenotype.

Prevalent distribution and survival outcome of HPV infection in patients with early-stage cervical cancer in Hangzhou, China

Abstract Objectives To describe the prevalent distribution of human papilloma virus (HPV) infection in patients with early-stage cervical squamous cell carcinoma (CSCC). To provide data on high-risk HPV (HR-HPV) infection and other clinicopathological factors for their correlations with the survival of CSCC patients. Methods A total of 1425 patients with FIGO stages IA to IIA CSCC who underwent radical surgery between September 2008 and December 2012 were enrolled in the study. The prevalent distribution of HPV infection with different patient characteristics and survivals were analyzed with or without propensity score matching (PSM). Results The overall infection rate of HPV was 84.3%, including 13 carcinogenic HR-HPV genotypes and 8 low-risk HPV genotypes with infection rates of 82.6% and 5.8%, respectively. The distribution of HPV infection were proportional in patients with either different age groups or different FIGO stages. HPV16 was the dominant subtype with an infection rate of 65.1%, followed by the other top four subtypesHPV58 (8.7%), 18 (7.7%) and 52 (4.5%). χ2 analysis revealed that increased preoperative serum squamous cell carcinoma antigen levels and lymphovascular space invasion (LVSI) were statistically associated with HPV status. However, regression analyses indicated that only deep stromal invasion, LVSI and lymph node metastasis were independent prognostic factors on 5-year overall survival (OS), but not HR-HPV infection status even in the second exploratory analysis (P = 0.939) based on the PSM applied to reduce selection bias. Conclusions This study provided baseline data on the prevalence characteristics of HPV infections in patients with early-stage CSCC, and HR-HPV infection was not a prognosticator of 5-year OS, other than FIGO stage, LVSI and lymph node metastasis.

Epidemiological study of HPV infection in 40,693 women in Putian: a population study based on screening for high-risk HPV infection

Abstract Background The infection rate of human papillomavirus (HPV) is high in the coastal regions of China. However, the infection rate among high-risk genotypes of women in Putian City is unknown. Therefore, this study aimed to analyse the epidemiology of high-risk HPV infection among women in Putian and provide a reference for the diagnosis, treatment and vaccination of cervical cancer in this region. Methods The data used were obtained from the Chinese government’s public health program (“Cervical and Breast Cancer Screening Project”). A total of 40,693 female cervical cell exfoliation samples screened for high-risk HPV at the Affiliated Hospital of Putian University from July 2020 to December 2021 were enrolled. DNA was extracted using a fully automatic extractor. Then, 14 high-risk genotypes of HPV were detected by polymerase chain reaction. The characteristics of HPV infection, distribution of high-risk genotypes, infection types and thinprep cytologic test (TCT) classification at different age groups were analysed. Results Among the 40,693 samples, 3899 were infected with HPV, with an infection rate of 9.6%. Accordingly, HPV infection rates gradually increased with age, and statistically significant differences were observed among age groups (χ2 = 74.03, P &lt; 0.01). The infection rates of high-risk HPV52, HPV58 and HPV16 were in the top three and increased with age. Single infection was dominant (84.7%), followed by double infections (12.7%). The cervical cytology of 3899 HPV-positive people can be classified into negative for intraepithelial lesion and malignancy (NILM, 88.0%), atypical squamous cells of undetermined significance (ASC-US, 6.6%), atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H, 1.4%), low-grade squamous intraepithelial lesion (LSIL, 3.2%) and high-grade squamous intraepithelial lesion (HSIL, 0.8%). HPV16 infection rate increased with increasing severity of cervical cytology (χ2trend = 43.64, P &lt; 0.01), whereas the infection rates of HPV52 (χ2trend = 13.89, P &lt; 0.01) and HPV58 (χ2trend = 13.50, P &lt; 0.01) showed opposite trends. Conclusion The infection rate of female HPV high-risk screening in this region was 9.6% and mainly involved single infections. In addition, HPV16, HPV52 and HPV58 were closely related to the severity of cervical cytology. Effective screening, vaccination and education are needed. The 9-valent vaccine will be effective in reducing cervical pre-invasive disease. It would also be reasonable to state that the rising trend in HPV infection and high grade cytology with age emphasises the need to target older women with screening. Vaccination of younger women (aged ≤ 25) will lay the foundation for better cancer outcomes in the future.

Genetic diversity in L1 ORF of human papillomavirus in women with cervical cancer with and without human immunodeficiency virus in Botswana and Kenya

Abstract Background The variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Nucleotide changes within the L1 gene, nucleotide variability, and phylogeny were explored in relation to HIV in samples from Botswana and Kenya. Methods A total of 98 HPV-positive cervical samples were sequenced to identify different HPV variants. Phylogenetic inferences were used to determine HPV genotypes and investigate the clustering of sequences between women living with HIV (WLWHIV) and -women not living with HIV (WNLWHIV). Results Out of 98 generated sequences, 83.7% (82/98) participants had high-risk (HR) HPV genotypes while 16.3% (16/98) had low-risk (LR) HPV genotypes. Among participants with HR-HPV genotypes, 47.6% (39/82) were coinfected with HIV. The prevalence of HR-HPV genotypes was statistically higher in the Botswana population compared to Kenya (p-value &lt; 0.001). Multiple amino acid mutations were identified in both countries. Genetic diversity differed considerably among WLWHIV and WNLWHIV. The mean pairwise distances between HPV-16 between HIV and HIV/HPV as well as for HPV-18 were statistically significant. Six (6) new deleterious mutations were identified in the HPV genotypes based on the sequencing of the L1 region, HPV-16 (L441P, S343P), HPV-18 (S424P), HPV-45 (Q366H, Y365F), and HPV-84 (F458L). The majority of the patients with these mutations were co-infected with HIV. Conclusions Genomic diversity and different genomic variants of HPV sequences were demonstrated. Candidate novel mutations within the L1 gene were identified in both countries which can be further investigated using functional assays.

A rare case of peritoneal tuberculosis mimicking peritoneal carcinomatosis: the ongoing challenge

Abstract Tuberculosis (TB) is a serious infection that can involve any organ system and present in various forms. About one-third of the world’s population are carriers of latent TB. Although most cases are from a pulmonary origin, there is a rising prevalence of abdominal TB. Patients with pulmonary or extrapulmonary TB are treated similarly through the use of pharmacological therapy. Nonspecific clinical manifestations of TB have made it difficult for clinicians to diagnose. Peritoneal tuberculosis (PTB) is a serious concern as its symptoms overlap with that of many other chronic conditions, especially in those who are immunocompromised. The lack of highly sensitive and specific testing methods has made early intervention difficult, therefore a high index of suspicion is crucial in the progression of the disease. Here, we present a case of a 71-year-old female with a history of abdominal pain, fever, and weakness. Initial investigation with computed tomography (CT) imaging revealed omental fat stranding that pointed towards peritoneal carcinomatosis (PC) from possible recurrence of her ovarian cancer. Further investigation with a peritoneal biopsy was remarkable for caseating granulomas with fat necrosis confirming extrapulmonary TB. This report highlights a rare case of PTB mimicking PC in an elderly patient who is immunocompromised from the use of long-term corticosteroids who continued to decline after pharmacological treatment of the disease.

Risk stratification and conservative management of women aged 25–40 years with cervical intraepithelial neoplasia grade 2(CIN2)

Cervical intraepithelial neoplasia grade 2 (CIN2) can progress to CIN3 or worse (CIN3 We conducted a retrospective observational study of 307 women aged ≤ 40 years, diagnosed with CIN2 via colposcopy-guided punch biopsy where the squamocolumnar junction was visible, and who underwent LEEP within three months. We compared the diagnoses from punch biopsies with the histology of the LEEP specimens and developed a stratified management algorithm based on identified risk factors. The risk of CIN3 Patients aged 25-40 years with CIN2 diagnosed in punch biopsy exhibited a substantial risk of CIN3

Association between contextual factors and vaccine coverage against human papilomavirus in adolescents in the state of Minas Gerais, Brazil: global spatial regressions

This study aimed to identify the associations between socioeconomic factors, the social environment, and human papillomavirus (HPV) vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This ecological study utilized secondary data from 853 municipalities in MG, covering female adolescents from 2014 to 2022 and male adolescents from 2017 to 2022, as provided by the information system of the National Immunization Program. Spatial statistical analysis was conducted to assess spatial dependence and identify spatial clusters of municipalities with high and low HPV vaccine coverage. The first and second dose coverage among male adolescents in most municipalities in MG was classified as very low (< 50%) or low (≥ 50% to < 80%). Among female adolescents, the majority of coverage rates were adequate (≥ 80%) or low (≥ 50% to < 80%). Socioeconomic factors, area-specific factors, and their interactions may influence HPV vaccination rates. The disparities in vaccination coverage rates observed across the state highlight the need for targeted interventions to increase coverage and reduce health issues, such as cervical cancer.

High frequency of alpha7-HPV in Colombian Caribbean coast women: cervical cancer screening analysis

SUMMARY Background Cervical cancer (CC) is a significant global public health concern, particularly in developing countries such as Colombia. The main risk factor involves high-risk HPV types (HR-HPV) infection, coupled with population-specific variables. The Caribbean region in Colombia lacks research on HR-HPV-type frequencies. Therefore, this study aims to establish the prevalence of type-specific HR-HPV and its association with sociodemographic factors among women undergoing cervical cytology screening. Methods A cross-sectional study involving voluntary women who provided informed consent and completed a questionnaire capturing sociodemographic, clinical, and sexual behavior information was conducted. All participants underwent cervical cytology and molecular analysis. Generic HPV detection employed three simultaneous PCRs (GP5+/6+, MY09/11, and PU1R/2 M), and positive samples were genotyped using the Optiplex HPV Genotyping kit. The analysis encompassed the 12 types of high-risk HPV (HR-HPV-16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58, and − 59). Frequencies were reported based on geographic subregions within the Córdoba department, and disparities were made between single and multiple infections. Sociodemographic and clinical variables were subjected to ordinal logistic regression, with statistical significance at a p-value &lt; 0.05. The statistical analyses utilized STATA 14® and R-Core Team-software. Results We included 450 women, mean age 40 (SD$$\pm$$11.44). PCR analysis revealed 43% HPV-positive (n=192). GP5+/6+ detected the most positives at 26% (n=119), followed by PU1R/2 M at 22% (n = 100) and MY09/11 at 15% (n=69). Multiple infections occurred in 87.3% (n=142), primarily 2 to 4 types (47.37%, n=90). Dominant types were HPV-18 (15.6%, n=61), HPV-16 (14.9%, n=58), HPV-31 (13.0%, n = 51), and HPV-45 (11.5%, n=45). Logistic regression identified age above 60 as a risk for concurrent multiple types (OR=6.10; 95% CI 1.18–31.63). Menopause was protective (OR=0.31; 95% CI 0.11–0.89). Conclusions Our study reveals a notable prevalence of multiple (2–4) high-risk HPV infections among adult women engaged in CC detection initiatives. Predominantly, α7 species constitute the prevalent HR-viral types, with the Medio Sinú subregion showing elevated prevalence. Menopausal status confers protection against diverse HR-HPV infections. Nevertheless, advancing age, particularly beyond 60 years, is linked to an increased susceptibility to simultaneous infections by multiple HPV-types.

Urine collection in cervical cancer screening – analytical comparison of two HPV DNA assays

Abstract Background To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women’s acceptance of urine collection and preferences towards the different sampling procedures. Methods One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa ( k ) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference. Results With the COBAS assay, urine showed good concordance to the vaginal ( k  = 0.66) self-samples and cervical samples ( k  = 0.66) for hrHPV detection. The corresponding concordance was moderate ( k  = 0.59 and k  = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure. Conclusions Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.

Effectiveness of HPV vaccination against the development of high-grade cervical lesions in young Japanese women

Abstract Background Although more than 10 years have passed since HPV vaccination was implemented, first as an interim programme (Emergent vaccine promotion programme) in November 2010, followed by incorporating into the National Immunization Programme in April, 2013 and suspended in June 2013, limited studies have investigated the HPV vaccine effectiveness against high-grade cervical lesions in Japan. Methods We collected the matched data of the results of cervical biopsy and history of vaccination from the Japan Cancer Society database. The subjects were women aged 20 to 29 years screened for cervical cancer between April, 2015 and March, 2017, and with information on HPV vaccination status. We estimated the relative risk of developing high-grade cervical lesions in vaccinated subjects using Poisson regression as compared to unvaccinated subjects. Results Among the 34,281 women screened, 3770 (11.0%) were vaccinated. The prevalence of CIN2+ was statistically significantly lower in the vaccinated women as compared to the unvaccinated women (Vaccine Effectiveness (VE) =76%; RR = 0.24, 95% CI:0.10–0.60). High VE against CIN3+ was also observed (91%; RR = 0.09, 95% CI:0.00–0.42). Conclusion Women aged 20–29 years who received at least one dose of HPV vaccine had a significantly lower risk of high-grade cervical lesions than those not vaccinated. In Japan, HPV vaccination should be resumed in order to reduce the incidence of cervical cancer.

Conservative management of CIN2 p16 positive lesions in women with multiple HPV infection

Abstract Background According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy, addressing the impact of routine use of p16 immunohistochemistry in this population and identify appropriate criteria for patient selection with the aim of reducing over-treatment. Method We studied the medical records of 130 patients who had undergone laser therapy for CIN2. Each patient underwent colposcopy, biopsy and HPV test and were tested for p16 protein,. Patients were divided based on HPV infection into: single infections, multiple infections. All patients underwent ZTA laser therapy with follow-up (2-year follow-up). Statistical analysis Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p  &lt; 0.05 were considered statistically significant. Results Single infections had a histological regression of 61.8% (21/34) and a histological persistence rate of 35.3% (12/34), which was greater than the multiple infection rate. The common characteristic that the women with persistence and progression had was the dimension of the lesion and the genotype 16. Ten cases of histological persistence and the only case of progression had one lesion greater than three quarters of the cervix. Conclusions With the progress of our understanding of the natural history of infection from human papillomavirus and the increasing use of colposcopy, thanks to the addition of HPV genotyping and the technique of immunohistochemistry, conservative management of these lesions is now possible.

Evaluation of the effectiveness of high-risk human papilloma self-sampling test for cervical cancer screening in Bolivia

Abstract Background In Bolivia the incidence and mortality rates of uterine cervix cancer are the highest in America. The main factor contributing to this situation is the difficulty of establishing and maintaining quality prevention programs based on cytology. We aimed to evaluate the effectiveness of HR-HPV testing on self-collected samples to detect cervical intra-epithelial neoplasia and identify the best combination of screening tests. Methods A total of 469 women, divided in two groups, were included in this study. The first group included 362 women that underwent three consecutively primary screening tests: self-collected sampling for HR-HPV detection, conventional cervical cytology and visual inspection under acetic acid (VIA). The second group included 107 women referred with a positive HR-HPV test that underwent conventional cervical cytology and VIA. The presence of high grade intraepithelial lesion (CIN 2+) or invasive cancer was verified by colposcopy and biopsy. Result In the screening group the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer were 100, 76, 44% for the VIA, HR-HPV test and cytology, respectively. In the referred group, the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer by VIA and cytology were 100 and 81%, respectively. Conclusions VIA and HR-HPV self-sampling were the best combination to detect CIN2+ lesions. Cytology analysis gave the poorest performance.

Viral load and high prevalence of HR-HPV52 and 58 types in black women from rural communities

AbstractBackgroundThe high-risk human papillomavirus (HR-HPV) infection is the main cause of cervical cancer development, and the most common types were included in the last approved nonavalent vaccine (9vHPV). Geographical, socioeconomic and ethnic barriers in developing countries challenge primary and secondary prevention measures of cervical cancer. We aimed to determine the prevalence of HPV infection and the viral load of HR-HPV 9vHPV-related types black women resident in rural semi-isolated communities.MethodsA descriptive study was conducted with 273 cervical samples of women from rural communities of Southeastern Brazil. Viral DNA was amplified by PCR, the genotype was identified by Reverse Line Blot (RLB) and Restriction Fragment Length Polymorphism (RFLP), and real-time PCR was applied to determine the viral load.ResultsHPV frequency was 11.4% (31/273), associated with the presence of cytological abnormalities (32.3%;p &lt; 0.001). Thirty-one distinct genotypes were detected; HR-HPV occurred in 64.5% (20/31) of the samples and the most prevalent type were HPV52 &gt; 58, 59. Multiple infections occurred with up to nine different genotypes. The viral load of HR-HPV 9vHPV-related types was higher in lesions than in normal cytology cases (p = 0.04); “high” and “very high” viral load occurred in HSIL and LSIL, respectively (p = 0.04).ConclusionsWe highlight that despite the low HPV frequency in the black rural women population, the frequency of HR-HPV was high, particularly by the HR-HPV52 and 58 types. Moreover, the HR-HPV viral load increased according to the progression from normal to lesion, being a potential biomarker to identify those women at higher risk of developing cervical lesions in this population.

Cervical cancer screening uptake and its predictors among women aged 30–49 in Ghana: Providing evidence to support the World Health Organization’s cervical cancer elimination initiative

Cervical cancer remains a global health challenge, disproportionately affecting women in low- and middle-income countries, including Ghana. Hence, this study examined the regional variations and predictors of cervical cancer screening uptake among women aged 30-49 in Ghana. Data for this study was obtained from the 2022 Ghana Demographic and Health Survey, comprising 7,124 women aged 30-49. The regional variations in women's uptake of cervical cancer screening was presented using spatial map. A mixed-effect multilevel binary logistic regression was used to examine the factors associated with cervical cancer screening uptake. The results were presented using adjusted odds ratios (aORs) with 95% confidence intervals (CIs). The uptake of cervical cancer screening was 7.27% [6.33, 8.35] in Ghana. Significant variations in cervical cancer screening existed across regions, with the lowest uptake in Western, Oti, Savannah, and North East regions. Women in rural areas had lower odds of being screened for cervical cancer [aOR = 0.46; 95% CI = 0.28, 0.76] compared to those in urban areas. Women living in the Central, Greater Accra, Volta, Eastern, Ashanti, Ahafo, Bono East, Oti, Northern, North East, Upper East, and Upper West regions all had higher odds of undergoing cervical cancer screening compared to those in the Western region. Women with higher education [aOR = 2.71; 95% CI = 1.23, 5.94] were more likely to be screened for cervical cancer compared to those with no formal education. Women who visited a health facility in the past year had higher odds of being screened for cervical cancer [aOR = 1.48; 95% CI = 1.02, 2.15] relative to those who did not. Reading newspapers or magazines increased the odds of cervical cancer screening uptake [aOR = 1.80; 95% CI = 1.10, 2.92] . Women who belonged to the middle [aOR = 2.19; 95% CI = 1.07, 4.49], richer [aOR = 2.85; 95% CI = 1.28, 6.38], and richest [aOR = 3.08; 95% CI: 1.25, 7.59] wealth indices were more likely to be screened for cervical cancer compared to those in the poorest wealth index. Our findings highlight critical disparities in cervical cancer screening uptake in Ghana, particularly emphasizing the need for targeted interventions to address the lower screening rates among women in the Western, Oti, Savannah, and North East regions. The significant association between cervical cancer screening uptake and healthcare access, media exposure, and wealth underscores the importance of enhancing healthcare infrastructure and outreach in underserved regions. To improve screening rates, it is recommended that public health initiatives focus on increasing awareness through community education programs, promoting health facility visits, and leveraging media platforms to disseminate information about cervical cancer screening. Additionally, policies should aim to reduce geographical and socioeconomic barriers, ensuring equitable access to screening services across all regions, especially for women in lower wealth quintiles.

Public health impact and cost effectiveness of routine and catch-up vaccination of girls and women with a nine-valent HPV vaccine in Japan: a model-based study

Abstract Background Combined with cancer screening programs, vaccination against human papillomavirus (HPV) can significantly reduce the high health and economic burden of HPV-related disease in Japan. The objective of this study was to assess the health impact and cost effectiveness of routine and catch-up vaccination of girls and women aged 11–26 years with a 4-valent (4vHPV) or 9-valent HPV (9vHPV) vaccine in Japan compared with no vaccination. Methods We used a mathematical model adapted to the population and healthcare settings in Japan. We compared no vaccination and routine vaccination of 12–16-year old girls with 1) 4vHPV vaccine, 2) 9vHPV vaccine, and 3) 9vHPV vaccine in addition to a temporary catch-up vaccination of 17–26 years old girls and women with 9vHPV. We estimated the expected number of disease cases and deaths, discounted (at 2% per year) future costs (in 2020 ¥) and discounted quality-adjusted life years (QALY), and incremental cost effectiveness ratios (ICER) of each strategy over a time horizon of 100 years. To test the robustness of the conclusions, we conducted scenario and sensitivity analyses. Results Over 100 years, compared with no vaccination, 9vHPV vaccination was projected to reduce the incidence of 9vHPV-related cervical cancer by 86% (from 15.24 new cases per 100,000 women in 2021 to 2.02 in 2121). A greater number of cervical cancer cases (484,248) and cancer-related deaths (50,102) were avoided through the described catch-up vaccination program. Routine HPV vaccination with 4vHPV or 9vHPV vaccine prevented 5,521,000 cases of anogenital warts among women and men. Around 23,520 and 21,400 diagnosed non-cervical cancers are prevented by catch-up vaccination among women and men, respectively. Compared with no vaccination, the ICER of 4vHPV vaccination was ¥975,364/QALY. Compared to 4vHPV, 9vHPV + Catch-up had an ICER of ¥1,534,493/QALY. Conclusions A vaccination program with a 9-valent vaccine targeting 12 to 16 year-old girls together with a temporary catchup program will avert significant numbers of cases of HPV-related diseases among both men and women. Furthermore, such a program was the most cost effective among the vaccination strategies we considered, with an ICER well below a threshold of ¥5000,000/QALY.