mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer.

Cervical cancer is one of the most frequent cancers in women and is associated with human papillomavirus (HPV) in 70 % of cases. Cervical cancer occurs because of progression of low-differentiated cervical intraepithelial neoplasia through grade 2 and 3 lesions. Along with the protein-coding genes, long noncoding RNAs (lncRNAs) play an important role in the development of malignant cell transformation. Although human papillomavirus is widespread, there is currently no well-characterized transcriptomic signature to predict whether this tumor will develop in the presence of HPV-associated neoplastic changes in the cervical epithelium. Changes in gene activity in tumors reflect the biological diversity of cellular phenotype and physiological functions and can be an important diagnostic marker. We performed comparative transcriptome analysis using open RNA sequencing data to assess differentially expressed genes between normal tissue, neoplastic epithelium, and cervical cancer. Raw data were preprocessed using the Galaxy platform. Batch effect correction, identification of differentially expressed genes, and gene set enrichment analysis (GSEA) were performed using R programming language packages. Subcellular localization of lncRNA was analyzed using Locate-R and iLoc-LncRNA 2.0 web services. 1,572 differentially expressed genes (DEGs) were recorded in the "cancer vs. control" comparison, and 1,260 DEGs were recorded in the "cancer vs. neoplasia" comparison. Only two genes were observed to be differentially expressed in the "neoplasia vs. control" comparison. The search for common genes among the most strongly differentially expressed genes among all comparison groups resulted in the identification of an expression signature consisting of the CCL20, CDKN2A, CTCFL, piR-55219, TRH, SLC27A6 and EPHA5 genes. The transcription level of the CCL20 and CDKN2A genes becomes increased at the stage of neoplastic epithelial changes and stays so in cervical cancer. Validation on an independent microarray dataset showed that the differential expression patterns of the CDKN2A and SLC27A6 genes were conserved in the respective gene expression comparisons between groups.

Decoding dysregulated genes, molecular pathways and microRNAs involved in cervical cancer.

BACKGROUND: The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have investigated the disease-associated genes along with the Gene Ontology, survival prognosis, transcription factors and the microRNA (miRNA) that are involved in cervical carcinogenesis, enabling a deeper comprehension of cervical cancer linked to HPV. METHODS: We used 10 publicly accessible Gene Expression Omnibus (GEO) datasets to examine the patterns of gene expression in cervical cancer. Differentially expressed genes (DEGs), which showed a clear distinction between cervical cancer and healthy tissue samples, were analyzed using the GEO2R tool. Additional bioinformatic techniques were used to carry out pathway analysis and functional enrichment, as well as to analyze the connection between altered gene expression and HPV infection. RESULTS: In total, 48 DEGs were identified to be differentially expressed in cervical cancer tissues in comparison to healthy tissues. Among DEGs, CCND1, CCNA2 and SPP1 were the key dysregulated genes involved in HPV-associated cervical cancer. The five common miRNAs that were identified against these genes are miR-7-5p, miR-16-5p, miR-124-3p, miR-10b-5p and miR-27a-3p. The hub-DEGs targeted by miRNA hsa-miR-27a-3p are controlled by the common transcription factor SP1. CONCLUSIONS: The present study has identified DEGs involved in HPV-associated cervical cancer progression and the various molecular pathways and transcription factors regulating them. These findings have led to a better understanding of cervical cancer resulting in the development and identification of possible therapeutic and intervention targets, respectively.

Variant analysis of human papillomavirus type 52 in Iranian women during 2018-2020: A case-control study.

Background and Aims: Knowing the regional variants of distinct human papillomavirus (HPV) types is valuable as it can be beneficial for studying their epidemiology, pathogenicity, and evolution. For this reason, the sequence variations of the E6 gene of HPV 52 were investigated among women with normal cervical cytology and premalignant/malignant cervical samples. Methods: Sixty-four HPV 52-positive samples were analyzed using semi-nested PCR and sequencing. Results: Our findings showed that all samples belonged to lineage A (61%) or B (39%). Among samples that were infected with the A lineage, sublineages A1 and A2 were detected and sublineage A1 was dominant. No association was found between lineages and stage of disease (p > 0.05). Conclusion: Our results revealed that the A lineage, sublineage A1, and B lineage were common in Iranian women. Nevertheless, more studies with larger sample sizes are required to estimate the pathogenicity risk of HPV 52 lineages in Iranian women with cervical cancer.

A systematic review of interventions to promote human papillomavirus (HPV) vaccination in Africa.

OBJECTIVE: We conducted a systematic review to assess the scope and effectiveness of interventions to improve human papilloma virus (HPV) vaccination in Africa from 2006 to 2021. STUDY DESIGN: Systematic review. METHODS: Four databases (Medline, Embase, CINAHL and PsycINFO) were searched for articles published between 2006 and 2021. Articles were screened and included based on eligibility criteria using DistillerSR (Version 2.35). Data were extracted and reported using a narrative synthesis. A quality assessment was also conducted for each study using validated quality appraisal tools. RESULTS: Out of 7603 articles identified by a systematic search, 18 articles met the inclusion criteria. Included studies comprised impact evaluation and cross-sectional studies published between 2012 and 2021 and conducted in eight African countries namely: Nigeria, Cameroon, South Africa, Kenya, Tanzania, Zambia, Mali, and Malawi. Study quality ranged from high to low quality. Interventions comprised fifteen educational and three multicomponent interventions. Out of thirteen impact evaluation studies (all educational interventions), twelve studies were effective in increasing HPV vaccine uptake and/or improving participants' knowledge, attitudes, and perceptions about the vaccine. Across five cross-sectional studies (two educational and three multicomponent interventions), HPV vaccine uptake rates ranged from 34% to 93.3%, with a consensus on safety and effectiveness in 67.9%-90.3% of participants post-intervention. CONCLUSION: Educational and multicomponent interventions have been implemented to improve HPV vaccination in Africa. While educational interventions have proven effective at improving HPV vaccine uptake, a more diverse range of interventions with robust impact evaluation study designs are needed to strengthen the available evidence and improve vaccine uptake.

STEPS (Study To Examine Parent, Patient/Dental Provider Systems) to Prevent Human Papillomavirus (HPV)-Related Cancers: A Piloted Dental Patient and Provider Evaluation of Current and Future HPV Education.

Oropharyngeal human papillomavirus (HPV) cancers are prevalent, but HPV education in dental clinics is uncommon. The purpose of this study was to evaluate dental provider and patient knowledge from, attitudes towards, and preferences for HPV education, then assess perceptions of existing HPV educational materials for use at dental visits. Appalachian Ohio dental patients (n = 13) and general/pediatric dental providers (n = 10) completed an initial, close-ended survey on current HPV knowledge and HPV educational attitudes, participation, and resource preferences. Select individuals reviewed existing HPV educational videos and toolkits via virtual focus groups (n = 9) or independent review surveys (n = 6). Using a discussion guide, participants responded to overall, visual, auditory, and content satisfaction statements, orally (focus groups) or with Likert scales (independent reviews). Surveys were summarized with frequencies/percentages; transcripts were qualitatively coded to identify potential material modifications. Dental providers and patients were more comfortable with HPV and oral cancer education (87% and 96%, respectively) and screening (96%) than with HPV vaccine education (74%) and referrals (61%) during dental visits. Providers were neither sharing HPV educational materials (80%) nor initiating educational conversations with dental patients (100%). The American Cancer Society videos and the "Team Maureen" toolkit were the most liked resources (i.e., fewer negative/disagree statements) by all participant groups. Findings indicate that future dental HPV educational efforts should be informed by currently available materials. Additional interventions are needed to promote dental provider discussions and sharing of educational materials with patients to increase education and promotion of the HPV vaccine and reduce oropharyngeal cancers.

Assessing bias in the causal role of HPV in oral cancer: A systematic review and meta-analysis.

OBJECTIVE: High-risk human papillomaviruses (HPV) are an established cause of oropharyngeal cancer. Their relationship with oral cancer remains unclear with detection ranging from 0% to 100%. HPV DNA detection or evidence of exposure alone is insufficient to conclude causality. This systematic review assesses the extent of bias in studies of HPV detection in cancers of the oral cavity. METHODS: PubMed, Ovid MEDLINE, EMBASE, and PsycInfo databases were searched for observational studies reporting the effect of HPV in oral cavity specific cancers. RESULTS: All 15 included studies presented HPV DNA detection or serum HPV-antibodies, none included mRNA E6/E7 analysis. Cases with oral cancer had 5.36 times (95% CI 3.29-8.72) higher odds of having HPV detected compared to controls. The odds of HPV detection were higher in cell-based (OR 6.93; 95% CI 0.82-58.55) and tissue samples (OR 5.28; 95% CI 3.41-8.18) than blood-based samples (OR 3.36; 95% CI 1.53-7.40). CONCLUSION: When cancer site is clearly differentiated between oropharynx and oral cavity, 12 studies showed strong association between HPV and oral cancer, but the available estimates lack internal validity due to inconsistent measurements, high confounding, and lack of gold standard testing. There is not high-quality evidence to conclude a causal relationship of HPV with oral cancer.

Clinical prognostic factors to guide treatment strategy for HPV­positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real­world experience.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed. All the patients were restaged according to the American Joint Committee on Cancer, 8th edition. The overall response rate and survival outcomes associated with clinical factors based on HPV status were analyzed using univariate and multivariate analyses. The present study analyzed 105 patients with a median age of 60 years (range, 40-76 years). Among 105 patients, 40 (38.1%) were HPV-negative and 65 (61.9%) HPV-positive. In all patients, survival outcomes were notably poorer in patients aged ≥60 years (P=0.006) and those who did not achieve complete response post-CRT (P<0.001), irrespective of the HPV status. The median relative dose intensity of IC was ≥80%, indicating adequate treatment, regardless of age. In contrast to patients with HPV-negative OPC, age ≥60 years (P=0.011) and T4 stage (P=0.019) emerged as substantial poor prognostic factors for survival outcomes in patients with HPV-positive OPC. Patients with HPV-positive OPC were categorized into three groups based on the number of clinical factors at diagnosis (such as age and T4 stage). The progression-free and overall survival showed significant stratification across each group as the number of high-risk factors increased despite IC and CRT. The findings indicated that patients with these high-risk factors require a cautious therapeutic strategy even when they are diagnosed with HPV-positive OPC, and the role of combined modality, including IC, will need to be investigated in a randomized trial to be routinely incorporated into clinical practice.

HPV status and immunohistochemical analysis of p16, p53 and PD­L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

Cervical HPV infection and related diseases among 149,559 women in Fujian: an epidemiological study from 2018 to 2023.

Objectives: To comprehensively analyze the epidemiological features of human papillomavirus (HPV) and HPV-related cervical diseases in females aged 35-64 years. Methods: A total of 149,559 samples of exfoliated cervical cells screened for HPV and related cervical lesions from January 2018 to December 2023 were enrolled. The prevalence of 15 high-risk and 6 low-risk HPV genotypes were detected, and the cervical cytology were analyzed. The impact of single and multiple HPV infections was characterized, and the effect of age was studied. Results: The cervix cytology was normal in 86.60% of the females, while 7.13% of the females were diagnosed with cervix inflammation, 0.60% with ASC-US, 0.22% with ASC-H, 0.72% with LSIL, 0.49% with HSIL, 0.03% with ICC. The highest median age was observed in ASC-H group with 54 years old. Females with primary school education or lower have the highest positive rates. The overall HPV prevalence was 8.60%. The relatively prevalent HPV types were HPV52, 58, 16, 39, 51. HPV16, HPV18, HPV58, HPV33 and HPV52 were the top5 predominant types in ICC patients. 17.41% females suffered from multiple HPV infection with the most frequently co-infection subtypes being HPV52, HPV58 and HPV16. The prevalence of all HPV subtypes increased with age. Multiple HPV infections accounted for a larger proportion in those aged above 55 years. The peak HPV16 prevalence was observed in ICC group in cases aged 45-49 and 55-59. The peak HPV33 prevalence was observed in younger individuals aged 40-44 who developed ICC. Conclusion: More action should be taken against HPV33 infection.

Cervical Cancer in Mexico: From a Renowned Vaccination Program to Unfulfilled Needs in Treatment Access.

Mexico's national human papillomavirus (HPV) vaccination program was established in 2008, providing free access to HPV vaccines and quickly becoming an immense success story, achieving significant coverage among young Mexican females. However, despite these efforts and notable achievements, cervical cancer caused mainly by HPV remains a challenging issue among Mexican women aged 15 years or older. A critical obstacle faced by women in the country is a lack of early detection and screening resources, coupled with delays in diagnosis and treatment, exacerbated by the poor distribution of already insufficient healthcare resources. This situation creates adverse conditions for the female demographic in the country. Our editorial aims to draw attention to the urgent need to improve access to adequate prevention, screening, and treatment for cervical cancer patients in Mexico, advocating for a collective effort between the Mexican government, public health professionals, and civil society.

Rationale and design of the Self-TI Study protocol: a cross-sectional human papillomavirus self-testing pilot study among transgender adults in England.

INTRODUCTION: Persistent infection with high-risk human papillomavirus (HPV) is the causal agent of several cancers including cervical, anal and oropharyngeal cancer. Transgender men and transmasculine non-binary (TMNB) people with a cervix are much less likely to undergo cervical cancer screening than cisgender women. Transgender women and transfeminine non-binary (TWNB) people assigned male at birth may be at increased risk of HPV. Both TMNB and TWNB people face many barriers to HPV testing including medical mistrust due to stigma and discrimination. METHODS AND ANALYSIS: The Self-TI Study (Self-TI) is a pilot study designed to measure acceptability and feasibility of HPV self-testing among transgender and non-binary people in England. TMNB people aged 25-65 years, with at least 1 year of testosterone, and TWNB people, aged 18 years and over, are eligible to participate. Participants self-collect up to four samples: an oral rinse, a first void urine sample, a vaginal swab (if applicable) and an anal swab. TMNB participants are asked to have an additional clinician-collected cervical swab taken following their routine Cervical Screening Programme sample. TWNB people are asked to take a self-collection kit to perform additional self-collection at home and mail the samples back to the clinic. Acceptability is assessed by a self-administered online survey and feasibility is measured as the proportion of samples returned in the clinic and from home. ETHICS AND DISSEMINATION: Self-TI received ethical approval from the Research Ethics Committee of Wales 4 and ethical review panel within the Division of Cancer Epidemiology and Genetics at the US National Cancer Institute. Self-TI was coproduced by members of the transgender and non-binary community, who served as authors, collaborators and members of the patient and public involvement (PPI) group. Results of this study will be shared with the community prior to being published in peer-reviewed journals and the PPI group will help to design the results dissemination strategy. The evidence generated from this pilot study could be used to inform a larger, international study of HPV self-testing in the transgender and non-binary community. TRIAL REGISTRATION NUMBER: NCT05883111.

Analysis of human papillomavirus type 16 E4, E5 and L2 gene variations among women with cervical infection in Xinjiang, China.

BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

Development of Promising Interventions to Improve Human Papillomavirus Vaccination in a School-Based Program in Quebec, Canada: Results From a Formative Evaluation Using a Mixed Methods Design.

BACKGROUND: Despite the availability of school-based human papillomavirus (HPV) vaccination programs, disparities in vaccine coverage persist. Barriers to HPV vaccine acceptance and uptake include parental attitudes, knowledge, beliefs, and system-level barriers. A total of 3 interventions were developed to address these barriers: an in-person presentation by school nurses, an email reminder with a web-based information and decision aid tool, and a telephone reminder using motivational interviewing (MI) techniques. OBJECTIVE: Here we report on the development and formative evaluation of interventions to improve HPV vaccine acceptance and uptake among grade 4 students' parents in Quebec, Canada. METHODS: In the summer of 2019, we conducted a formative evaluation of the interventions to assess the interventions' relevance, content, and format and to identify any unmet needs. We conducted 3 focus group discussions with parents of grade 3 students and nurses. Interviews were recorded, transcribed, and analyzed for thematic content using NVivo software (Lumivero). Nurses received training on MI techniques and we evaluated the effect on nurses' knowledge and skills using a pre-post questionnaire. Descriptive quantitative analyses were carried out on data from questionnaires relating to the training. Comparisons were made using the proportions of the results. Finally, we developed a patient decision aid using an iterative, user-centered design process. The iterative refinement process involved feedback from parents, nurses, and experts to ensure the tool's relevance and effectiveness. The evaluation protocol and data collection tools were approved by the CHU (Centre Hospitalier Universitaire) de Québec Research Ethics Committee (MP-20-2019-4655, May 16, 2019). RESULTS: The data collection was conducted from April 2019 to March 2021. Following feedback (n=28) from the 3 focus group discussions in June 2019, several changes were made to the in-person presentation intervention. Experts (n=27) and school nurses (n=29) recruited for the project appreciated the visual and simplified information on vaccination in it. The results of the MI training for school nurses conducted in August 2019 demonstrated an increase in the skills and knowledge of nurses (n=29). School nurses who took the web-based course (n=24) filled out a pretest and posttest questionnaire to evaluate their learning. The rating increased by 19% between the pretest and posttest questionnaires. Several changes were made between the first draft of the web-based decision-aid tool and the final version during the summer of 2019 after an expert consultation of experts (n=3), focus group participants (n=28), and parents in the iterative process (n=5). More information about HPV and vaccines was added, and users could click if more detail is desired. CONCLUSIONS: We developed and pilot-tested 3 interventions using an iterative process. The interventions were perceived as potentially effective to increase parents' knowledge and positive attitudes toward HPV vaccination, and ultimately, vaccine acceptance. Future research will assess the effectiveness of these interventions on a larger scale.

Los Angeles County dentists' opinions on discussing human papilloma virus-related oral health issues and recommending vaccine to patients.

Dentists are well-positioned to discuss oral health issues related to Human Papillomavirus (HPV) and recommend the HPV vaccine to their patients, mainly because the HPV virus causes oropharyngeal cancers.. We assessed Los Angeles (LA) County dentists' opinions on discussing HPV-related oral health issues and recommending the HPV vaccine to their patients. We tested if opinions differed between dentists whose primary patient population was only adults versus children and adults. We mailed a 19-item survey to 2000 randomly sampled LA County dentists for this cross-sectional study. The primary outcome variable was a summary opinion score of 7 opinion statements. We ran descriptive, bivariate comparisons and adjusted linear regression models. Overall, 261 dentists completed the survey. A majority (58.5%) worried they would lose patients if they recommended the vaccine; 49% thought dentists were not appropriate to educate, counsel, or advise on HPV-related issues; 42% were concerned about the safety of the vaccine; and 40% did not feel comfortable recommending the vaccine. The mean summary opinion score was 21.4 ± 5.4 for the total sample. Regression analysis showed no differences in opinions between dentists whose primary patient population was only adults versus children and adults (Coefficient = 0.146, p = 0.83). Overall, the responding dentists were not very favorable about discussing oral health-related HPV issues and recommending the HPV vaccine to their patients. Additionally, the overall opinions were similar between dentists whose primary patient population was only adults versus children and adults.

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009-2014.

Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009-2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV-1, and HSV-2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26-1.70; OR 1.09, 95% CI 1.05-1.13; OR 1.06, 95% CI 1.01 - 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29-1.77; OR 1.08, 95% CI 1.04-1.12; OR 1.05, 95% CI 1.01-1.10, respectively) after adjusting all relevant co-factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV-1 infection, while the relationship between HSV-2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years.

Awareness of cervical cancer risk factors and preventive approaches, and perceived causes of cervical cancer among secondary school girls: a cross-sectional study in Northern Uganda.

BACKGROUND: The majority of women in low- and middle-income countries have low awareness of cervical cancer. This study sought to establish awareness of cervical cancer risk factors and preventive approaches, as well as sources of information and perceived causes of cervical cancer among secondary school girls in northern Uganda. METHODS: This was a cross-sectional study conducted in rural northern Uganda. We collected data using an investigator administered pre-tested questionnaire. Analysis was done with STATA version 14.0. Multivariate analyses with logistic regressions models were used to determine magnitudes of association between independent and outcome variables. Odds ratios and accompanying 95% confidence intervals are reported. Statistical significance was considered if the two sided p-value <.05. RESULTS: Most participants (97%; n = 624) had heard of cervical cancer before this study. The most common source of information about cervical cancer was friends (31.1%; n = 194). More than half of the participants (59%; n = 380) had heard about a vaccine that prevents cervical cancer, but only a third (33%; n = 124) had ever received a dose of the vaccine. The majority of participants (89%; n = 550) reported that cervical cancer could be prevented; however only half (52%; n = 290) knew that vaccination of girls aged 9-13 years could prevent cervical cancer. The majority of participants did not recognize the risk factors for cervical cancer; for example, only 15% (n = 98), 7% (n = 45), and 1.4% (n = 9) recognized early onset of sexual intercourse, infection by the human papillomavirus (HPV), and smoking respectively. On adjusting for age, students' class, and religion, students in schools with school health programs were twice (aOR = 2.24: 95%CI; 1.24-4.06) more likely to know that cervical cancer is preventable. CONCLUSION: Secondary school girls need information on cervical cancer risk factors and approaches to prevention so that they may avoid exposures to the risk factors and promptly seek and undertake preventive approaches including HPV vaccinations.

Educational interventions through school health programs are viable strategies to improve the knowledge of secondary school girls on cervical cancer risk factors and preventive approaches.Peers/friends are key sources of information on cervical cancer to secondary school girls.Peers/friends are a sustainable strategic resource, and therefore students could be trained to provide peer training on cervical cancer risk factors and preventive approaches to fellow secondary school girls.

DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging.

Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1-6 CpG-sites), hTERT (1-10 CpG-sites) and FAM19A4 (1-5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

Pigmented acuminated condylomas seborrhoeic keratosis-like: a new entity?

BACKGROUND: Condyloma acuminatum is caused by human papillomavirus (HPV), which typically presents as excrescent, pedunculated, papillomatous lesions which may be of a pale colour. On rare occasions, we have observed pigmented genital lesions that are similar to seborrhoeic keratoses, but with histological findings of condyloma acuminatum and positive genotyping for HPV. We have termed these 'seborrhoeic keratosis-like' type condylomas. METHODS: This is an observational retrospective study. The following clinical data were collected: age, sex, time of evolution, location, isolated or multiple lesions, monomorphous or polymorphous/mixed lesions. HPV genotyping was performed in all cases, and excision for histological study in eight cases. RESULTS: A total of 31 patients were diagnosed with this type of pigmented condylomata acuminata. Of these, 16 had isolated lesions (less than five lesions) and 15 had multiple lesions. 67% of the lesions exhibited slow growth, with an evolution period of greater than 1 year. The most frequent location was the base of the penis and pubis. HPV genotyping of the lesions was positive in all cases, with the HPV-6 genotype predominating (28 cases, 90.3%). The lesions exhibited dermoscopic differences from other pigmented lesions and histological findings attributable to HPV infection (pseudoparakeratosis, koilocytosis, etc) and others similar to those observed in seborrhoeic keratoses. CONCLUSIONS: A total of 31 patients were diagnosed with pigmented verrucous lesions, excrescents, isolated or multiple, in the genital region. These lesions exhibited clinical characteristics similar to seborrhoeic keratoses, with positive genotyping for HPV. In the majority of cases, the genotype was HPV-6. These lesions have been named 'pigmented condylomata acuminata seborrhoeic keratosis-like'. Only 10 cases of these lesions have been described in the literature.

Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells.

Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against the Src canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC50) of HeLa cells to be 31.49 nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src (p < 0.001), phospho-Src (p < 0.001), Ras (p < 0.01), c-Raf (p < 0.001), ERK1 (p < 0.001), phospho-ERK1 (p < 0.001), phospho-ERK2 (p < 0.01), phospho-Mnk1 (p < 0.001), eIF4E (p < 0.01), phospho-eIF4E (p < 0.001), E6 (p < 0.01), E7 (p < 0.01), Rb (p < 0.01), phospho-Rb (p < 0.001), MDM2 (p < 0.01), E2F1 (p < 0.001), phospho-FAK (p < 0.001), phospho-p130 Cas (p < 0.001), Mcl-1 (p < 0.01), and Bcl-2 (p < 0.001), but upregulates cPARP (p < 0.001), and cPARP/fPARP (p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.

Tirbanibulin is Promising Novel Therapy for Human Papillomavirus (HPV)-associated Diseases.Tirbanibulin 1% ointment is an approved synthetic topical ointment for treating actinic keratoses (AK), a precancer of skin cancer. Topical tirbanibulin has previously been reported to clinically resolve human papillomavirus (HPV)-( +) diseases.In this study, we examine how tirbanibulin may affect the HPV and pathways associated with cancer.We treated the HeLa cell line to determine the effects on HPV cell proliferation. Increasing the concentration of tirbanibulin statistically significantly affected numerous cellular pathways often associated with cancer.These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins and thereby kill cancer cells.

Interferon alpha-2b treatment for exophytic nasal papillomas and human papillomavirus infection.

OBJECTIVES: Exophytic Sinonasal Papilloma (ESP) is a benign tumor of the sinonasal tract. Complete surgical excision by endoscopic surgery is the treatment of choice. However, a high recurrence rate (36% at 5-year follow-up) is associated with this method, which may indicate the presence of microorganisms such as Human Papillomavirus (HPV). It is important to note that the standard treatment for ESP does not include antiviral drugs. In our study, we are testing the effectiveness of an interferon-containing drug in reducing recurrence and postoperative reactions in patients with ESP. METHODS: We included 78 patients aged 23-83 years with a confirmed diagnosis of ESP by rhinoscopy and nasal endoscopy and a positive PCR test for HPV in nasal scrapings. To compare the results, we divided the patients into main and control groups. The main group received recombinant human interferon after surgery, while the control group did not receive the drug. We performed a statistical analysis to compare the proportion of patients without reactive manifestations at different stages of the postoperative period, as well as to compare the proportion of patients with recurrent ESP at certain stages of observation. RESULTS: The introduction of recombinant human interferon accelerated the resolution of postoperative reactions and promoted the healing of the nasal mucosa after surgical removal of the ESP. We also found a statistically significant association between treatment with recombinant interferon and a reduction in the recurrence rate of ESP. CONCLUSION: According to the results of the study, it was found that in the main group of patients who received rhIFN-α2b (recombinant human Interferon alpha 2b) in the postoperative period, the frequency of relapses of ESP and the time of postoperative recovery were significantly lower than in patients in the control group who did not take the drug. LEVEL OF EVIDENCE: Cohort Study.