Association between oral contraceptives and cervical cancer: A retrospective case-control study based on the National Health and Nutrition Examination Survey.

Background: Cervical cancer is the fourth most common cancer among females globally, with a high incidence and high mortality among females in developing countries. This retrospective case-control study aimed to investigate the association between oral contraceptives and cervical cancer, on which insufficient evidence still exists. Material and Methods: To examine the association between oral contraceptives and cervical cancer based on 7,496 females aged over 20 years from the National Health and Nutrition Examination Survey, multivariable logistic regression conducted from 1999 to 2016 was used. Results: Contraceptive use was positively associated with cervical cancer risk. In model 1 (unadjusted), a 195% increased risk of cervical cancer was observed among those who used oral contraceptives (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.39-3.98, p = 0.002) compared to those who did not. In addition, the ORs for the exposed population were 1.74 (95% CI = 1.05-3.08, p = 0.041) and 1.93 (95% CI = 1.16-3.44, p = 0.017) in model 2 (adjusted for age, race, and body mass index [BMI]) and model 3 (adjusted for education level, ratio of family income to poverty, drinking status, smoking status, number of pregnancies, age at first sex, number of sexual partners, and whether to receive the human papillomavirus (HPV) vaccine in addition to model 2), respectively. Furthermore, subgroup analyses stratified by age, smoking status, BMI, age at first sex, number of sexual partners, and whether to receive the HPV vaccine also revealed that oral contraceptives were significantly associated with cervical cancer. Conclusion: This study demonstrated that oral contraceptive use increased the risk of cervical cancer. In addition, the higher risk, including individuals older than 45 years, having a high BMI (≥30 kg/m2), being current smokers, and having more than five sexual partners, may contribute to the development of cervical cancer.

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

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

Lack of knowledge about the human papillomavirus vaccine among Brazilian adolescents: A cross-sectional study.

To analyze the distribution and factors associated with lack of knowledge about the human papillomavirus (HPV) vaccine among Brazilian adolescents.Cross-sectional study using the 2019 National School Health Survey among 17,805 Brazilian students of public and private schools, aged 13-17 years. The outcome variable was "lack of knowledge about the HPV vaccine" and the explanatory variables were sociodemographic, behaviors, knowledge, and health conditions. Logistic regression model was used to calculate Odds Ratio (OR) and 95% confidence intervals (95%CI). Spatial analysis techniques were used to determine the formation of clusters in the federated units with similar proportions of adolescents who were unaware of the vaccine. The lack of knowledge about the HPV vaccine was reported by 45.54% of Brazilian students. There was a higher chance of lack of knowledge having had sexual intercourse (OR 1.43; 95% CI 1.20-1.70); attending public school (OR 1.72; 95%CI 1.47-2.02) and located in the Northeast Region (OR 1.35; 95%CI 1.08-1.69). The lower chance of lack of knowledge were female gender (OR 0.41; 95% CI 0.35-0.48), higher maternal education (OR 0.62; 95% CI 0.50-0.77) self-rated health as Poor/very poor (OR 0.64; 95% CI 0.49-0.86) and receiving contraceptive counseling (OR 0.77; 95% CI 0.65-0.91). The proportion of lack of knowledge about the HPV vaccine was higher with the formation of High-High spatial clusters in the states of Maranhão, Piauí, and Pernambuco. Sociodemographic, health, and behavioral conditions and knowledge of students, as well as school characteristics, were associated with lack of knowledge about the HPV vaccine. A higher frequency of lack of knowledge about the HPV vaccine among adolescents was found in the states of the Northeastern Region.

The mutual interplay between NTRK fusion genes and human papillomavirus infection in cervical cancer progression (Review).

Cervical cancer is a significant global health concern, with a substantial portion of cases attributed to human papillomavirus (HPV) infection. Recent advancements in molecular profiling have identified distinct subtypes of cervical cancer based on their genomic alterations. One such subgroup is neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive cervical cancers, characterized by gene fusions involving the NTRK genes. Although both NTRK fusion genes and HPV infections are independently recognized as significant risk factors in cervical cancer, their interplay and mutual effects on cancer progression are not yet fully understood. The present review is the first of its kind to explore the potential interplay between NTRK fusion genes and HPV infections. It surveys in detail how their combined effect can influence the signaling pathways during cervical cancer development and progression. Moreover, the present study discussed the clinical features, histopathological examinations, treatment procedures and follow-up outcomes of NTRK-fusion gene-positive cervical cancer. The present review may help in the understanding of the management and treatment of such rare, lethal and resistant cervical cancers.

Optimal human papillomavirus vaccination strategies in the context of vaccine supply constraints in 100 countries.

Background: Countries are recommended to immunise adolescent girls routinely with one or two doses of human papillomavirus (HPV) vaccines to eliminate cervical cancer as a public health problem. With most existing vaccine doses absorbed by countries (mostly high-income) with existing HPV vaccination programmes, limited supply has been left for new country introductions until 2022; many of those, low- and middle-income countries with higher mortality. Several vaccination strategies were considered by the Strategic Advisory Group of Experts on Immunization to allow more countries to introduce vaccination despite constrained supplies. Methods: We examined the impact of nine strategies for allocating limited vaccine doses to 100 pre-introduction countries from 2020 to 2030. Two algorithms were used to optimise the total number of cancer deaths that can be averted worldwide by a limited number of doses (knapsack and decreasing order of country-specific mortality rates), and an unoptimised algorithm (decreasing order of Human Development Index) were used. Findings: Routinely vaccinating 14-year-old girls with either one or two doses and switching to a routine 9-year-old programme when supply is no longer constrained could prevent the most cervical cancer deaths, regardless of allocation algorithm. The unoptimised allocation averts fewer deaths because it allocates first to higher-income countries, usually with lower cervical cancer mortality. Interpretation: To optimise the deaths averted through vaccination when supply is limited, it is important to prioritise high-burden countries and vaccinating older girls first. Funding: WHO, Bill & Melinda Gates Foundation.

Manipulating host secreted protein gene expression: an indirect approach by HPV11/16 E6/E7 to suppress PBMC cytokine secretion.

Human papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.

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

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

A health decision analytical model to evaluate the cost-effectiveness of female genital schistosomiasis screening strategies: The female genital schistosomiasis SCREEN framework.

Female genital schistosomiasis is a chronic gynaecological disease caused by the waterborne parasite Schistosoma (S.) haematobium. It affects an estimated 30-56 million girls and women globally, mostly in sub-Saharan Africa where it is endemic, and negatively impacts their sexual and reproductive life. Recent studies found evidence of an association between female genital schistosomiasis and increased prevalence of HIV and cervical precancer lesions. Despite the large population at risk, the burden and impact of female genital schistosomiasis are scarcely documented, resulting in neglect and insufficient resource allocation. There is currently no standardised method for individual or population-based female genital schistosomiasis screening and diagnosis which hinders accurate assessment of disease burden in endemic countries. To optimise financial allocations for female genital schistosomiasis screening, it is necessary to explore the cost-effectiveness of different strategies by combining cost and impact estimates. Yet, no economic evaluation has explored the value for money of alternative screening methods. This paper describes a novel application of health decision analytical modelling to evaluate the cost-effectiveness of different female genital schistosomiasis screening strategies across endemic settings. The model combines a decision tree for female genital schistosomiasis screening strategies, and a Markov model for the natural history of cervical cancer to estimate the cost per disability-adjusted life-years averted for different screening strategies, stratified by HIV status. It is a starting point for discussion and for supporting priority setting in a data-sparse environment.

Evaluation of female university students' knowledge, attitudes, and practices toward human papillomavirus infection and vaccination. Multicenter cross-sectional study.

INTRODUCTION: Having good knowledge and a favorable attitude toward human papillomavirus (HPV) and HPV vaccinations is the cornerstone for increasing the use of HPV vaccinations and preventing cervical cancer. The objective of this study was to evaluate the level of knowledge, attitudes, and practices regarding HPV and HPV vaccinations, as well as to identify associated factors among female undergraduate health science students at both the University of Gondar (UoG) and Bahir Dar University (BDU), Amhara, Ethiopia. METHODS: Institutional-based multicenter descriptive cross-sectional study was conducted from June 1, 2023, to July 30, 2023. A multistage sampling technique was used to select 633 female undergraduate health science students, and data were collected using a structured, self-administered questionnaire. The data were coded, entered in Epi-data, and exported to SPSS for analysis. Variables with a P-value < 0.25 in the bivariate analysis were inserted in a multivariate logistic regression model, and those with a P-value of < 0.05 in the multivariate binary logistic regression were considered statistically significant factors for knowledge, attitude, and practice regarding HPV and vaccine against it. RESULTS: The study included 600 participants with a mean age of 20.8 ± 0.75 years. Using Bloom's cutoff points for the KAP study, among the participants, 436 (72.7%) had good knowledge about HPV, whereas 315 (52.5%) had good knowledge about HPV vaccinations. More than half of the participants, 359 (59.8%) heard about HPV vaccinations in Ethiopia. More than half of the participants, 342 (57%) had favorable attitudes toward HPV vaccinations. Only 261 (43.5%) participants believed the HPV vaccine was safe and effective. All participants had never been tested for HPV, and 471 (78.5%) refused to have their samples for regular HPV testing. The factors like ages between 21 and 23 years (AOR, 2.12, 95% CI: 1.22-3.09) and favorable attitudes toward HPV vaccinations (AOR: 1.88; 95%, CI: 1.15-3.41) were associated with the participant's knowledge about HPV vaccinations. Having good knowledge about the virus (AOR: 1.92; 95%, CI: 1.11-5.88) and its vaccine (AOR:1.60; 95%CI: 1.07-2.47) were factors associated with the attitude of the participants about HPV vaccinations. Additionally, HPV vaccination practice was significantly associated with the attitude of the participants toward HPV vaccinations (AOR: 1.85; 95%CI: 1.15-3.45), knowledge about HPV (AOR: 1.18; 95%CI: 0.55-5.50), and HPV vaccinations (AOR: 1.85; 95%CI: 1.08-2.44). CONCLUSION: This study revealed that half of the students had good knowledge and a favorable attitude toward HPV vaccinations, but there was poor HPV vaccination practice. There is still a need for continued health education, training, and counseling services for students to strengthen HPV vaccination practices, improve students' attitudes and knowledge about the benefits of vaccination, and improve counseling abilities against HPV-induced cancer.

Molecular findings and virological assessment of bladder papillomavirus infection in cattle.

Bovine and ovine papillomaviruses (BPVs - OaPVs) are infectious agents that have an important role in bladder carcinogenesis of cattle. In an attempt to better understand territorial prevalence of papillomavirus genotypes and gain insights into their molecular pathway(s), a virological assessment of papillomavirus infection was performed on 52 bladder tumors in cattle using droplet digital polymerase chain reaction (ddPCR), an improved version of conventional PCR. ddPCR detected and quantified BPV DNA and mRNAs in all tumor samples, showing that these viruses play a determinant role in bovine bladder carcinogenesis. OaPV DNA and mRNA were detected and quantified in 45 bladder tumors. BPV14, BPV13, BPV2, OaPV2, OaPV1, and OaPV3 were the genotypes most closely related to bladder tumors. ddPCR quantified BPV1 and OaPV4 DNA and their transcripts less frequently. Western blot analysis revealed a significant overexpression of the phosphorylated platelet derived growth factor ß receptor (PDGFßR) as well as the transcription factor E2F3, which modulate cell cycle progression in urothelial neoplasia. Furthermore, significant overexpression of calpain1, a Cys protease, was observed in bladder tumors related to BPVs alone and in BPV and OaPV coinfection. Calpain1 has been shown to play a role in producing free transcription factors of the E2F family, and molecular findings suggest that calpain family members work cooperatively to mutually regulate their protease activities in cattle bladder tumors. Altogether, these results showed territorial prevalence of BPV and OaPV genotypes and suggested that PDGFßR and the calpain system appeared to be molecular partners of both BPVs and OaPVs.

Association of opium use and tobacco smoking with α-, ß-, and γ-human papillomavirus oral infection.

Head and neck squamous cell carcinomas (HNSCCs) are linked to tobacco smoking, opium use, and human papillomavirus (HPV) infection. However, little is known about the association of HPV infection with risk factors of HNSCCs, including opium and tobacco use. This cross-sectional analysis of a national multi-center case-control study in Iran included 498 HNSCC cases and 242 controls. We investigated the association of opium and tobacco use with α- (n = 21), ß- (n = 46), and γ-HPV (n = 52) types in saliva samples using type-specific bead-based multiplex genotyping assays (TS-MPG). We found that α-HPV positivity was significantly associated with tobacco smoking (OR = 10.35; 95% CI = 1.15, 93; p = .03), but not with opium use (OR = 1.06; 95% CI = 0.41, 2.76; p = .89). Additionally, tobacco smoking correlated with an elevated risk of ß-species 2 HPV infection (OR = 1.28; 95% CI = 1.04, 1.58; p = .020). Conversely, opium use showed a positive association with γ-species 12 HPV infection (OR = 5.67; 95% CI = 1.43, 22.44; p = .013). These findings indicate that tobacco and opium use may influence the risk of HPV infection in different ways depending on the HPV genus and species. Further studies are needed to replicate these findings in other populations.

Time to take HPV infection in colorectal cancer patients more seriously.

Background: The association between viral infections and colorectal cancer (CRC) remains an enigma in cancer research. Certain types of Human Papillomaviruses (hr-HPVs), known for their oncogenic properties, have been observed in particular CRC biopsies, further adding to the enigma surrounding this association. Materials and methods: This cross-sectional study was conducted on 40 confirmed cases of CRC adenocarcinoma. The presence and genotyping of HPV DNA in colorectal fresh tissue and urine samples was assessed using an HPV DNA hybridization kit. A subset of serum samples from both CRC cases and healthy volunteers was randomly chosen and subjected to western blot to investigate the presence of HPV16 E6/E7 oncoproteins carried by exosomes. Results: It was observed that 26/40 HPV-positive CRC patients demonstrated 7 times more chance to develop colorectal cancer when compared to those 8/40 normal tissue (odds ratio [OR] = 7.4; confidence interval [CI] 95% = 0.483156-0.793718; p < 0.001). Of 26 HPV-positive CRC patients, 14 urine samples were also showed HPV DNA positivity (p = 0.013). High-risk HPV16 was the most prevalent genotype detected in both 24/40 tumor and 12/40 urine samples (p < 0.001). The tumor sample of a male was HPV45, while another male's urine sample was HPV31. A female CRC patient had HPV83 in tumor and HPV56 in urine. Here, was the first detection of HPV83 in a CRC patient. Notably among 20 randomly selected serum exosome samples, one serum sample concurrently tested positive for both HPV16 E6 and E7 oncoproteins, and one sample tested positive for HPV16 E7 oncoprotein. Conclusion: High risk HPV DNA detection in CRC urine samples supports non-invasive screening tools. Detection of HPV16 E6 and E7 oncoproteins in exosomes from serum samples shows potential for non-invasive diagnostics. HPV's potential role in CRC development is also underscored. HPV vaccination should be implemented in low- and middle-income countries to prevent cancer.

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.

Factors associated with human papillomavirus infections among women living with HIV in public health facilities in Western Oromia, Ethiopia.

BACKGROUND: Human Papillomavirus infection (HPV) is among the most common sexually transmitted infections with the highest incidence and prevalence worldwide. HPV has been established as the main cause of cervical cancer and remains a public health problem globally. In Western Oromia, Ethiopia cervical screening remains a major issue because of limited resources, and shortage of HPV testing technology. As a result, the prevalence of HPV and associated factors remain unknown among HIV-positive women. This study aimed to assess the prevalence of HPV and associated factors among women living with HIV attending Antiretroviral Therapy (ART) services in public health facilities of East Wollega and West Showa Zones, Ethiopia, 2022. METHOD: Using a cross-sectional study design, a total of 415 women ≥ 18 years old were enrolled using systematic random sampling from five public health facilities. Cervical specimens were collected by a trained nurse from April 01 2022, to May 30, 2022, and tested at Nekemte Public Health Research and Referral Molecular Biology, a certified/accredited laboratory for HPV-DNA Polymerase Chain Reaction by expertise using Abbott m2000rt-PCR assays. Finally, Epi data version 4.6 was used for data entry and SPSS version 24.0 were used for data cleaning and analysis, and frequencies and prevalence of HPV were computed. Variables were identified using the multivariable model and statistically significant associations of variables were determined based on the adjusted odds ratio (AOR) with its 95% CI and P-value < 0.05 to determine the strength of association. RESULT: The prevalence of HPV was 30.4% [95% CI: 26.0, 34.9]. Of HPV-infected women, 11.9% were positive for HPV-16, 9.5% for HPV-18, and 65.9% were positive for other hr-HPV . The odds of HPV infection among women aged beyond 48 years are 2.85 times the odds of HPV among people who were aged 18-27(AOR = 2.85, 95% CI: 1.16, 5.58). The odds of HPV infection among women who had three or more sexual partners is 4.12 times the odds of HPV infection among women with a single sexual partner(AOR = 4.12, 95% CI: 2.34-8.62). The odds of HPV infection among women who didn't use condom during sexual intercourse are 4.73 times the odds of HPV among women who used condom during sexual intercourse. (AOR = 4.73, 95% CI: 1.98-9.33). The odds of HPV infection among women who had history of is 4.52 times the odds of HPV infection among women with no history of abortion. [AOR = 4.52, 95% CI: 2.04, 6.89] The odds of HPV infection among women with history of Sexually Transmitted Infection (STI) 3.62 times the odds of HPV among women with no history of STI (AOR = 3.62, 95%CI: 1.75, 5.83). The odd of HPV among women with abnormal vaginal discharge is 3.31 times the odds of the disease among women with normal vaginal discharge [AOR = 3.31, 95% CI: 2.87,7.35). CONCLUSION AND RECOMMENDATION: The prevalence of HPV infection among HIV-infected women was high in the study area. Given the above-associated factors, we recommend that the stakeholders integrate HPV prevention strategies into HIV /AIDS services. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections, which may explain the high prevalence among HIV-infected women. This can contribute to policy development and planning of prevention strategies incorporating HPV infection prevention especially among youth and HIV-infected people.

Tracing human papillomavirus in skin and mucosal squamous cell carcinoma: a histopathological retrospective survey.

Worldwide, squamous cell carcinoma (SCC) incidence is rising. The literature debates the human papillomavirus (HPV)'s role in cutaneous SCC development. We examined HPV histopathology in SCC samples in this study. Retrospective study at tertiary referral skin center in 2020. Histopathological features of HPV, including koilocytosis, hyperkeratosis, acanthosis, hypergranulosis, parakeratosis, solar elastosis, papillomatosis, and tumor grade, were examined in SCC specimens. Two dermatopathologists independently reevaluated all samples. We examined 331 SCC cases (male:female ratio = 3.9:1). The mean age was 68.1, with 15.1 standard deviation. Lesions were most common on the face (40.5%), scalp (22.7%), and extremities (20.8%). Koilocytes were found in 50 (15.1%) lesions. Nail (38.1%, p=0.007), oral cavity (36.8%, p=0.014), and genitalia (60.0%, p=0.026) lesions had higher koilocytosis rates. SCCs were found in 6.6% of specimens, but in situ tumors had the highest koilocytosis (64.7%), significantly higher than other grades (p<0.001). SCC pathology often shows HPV and specific koilocyte histopathology. Well-differentiated SCC has a stronger association with nail, oral, and genital lesions.

Enhancing Cervical Cancer Screening with 7-Type HPV mRNA E6/E7 Testing on Self-Collected Samples: Multicentric Insights from Mexico.

Cervical cancer remains a significant public health issue, particularly in regions with low screening uptake. This study evaluates the effectiveness of self-sampling and the 7-type HPV mRNA E6/E7 test in improving cervical cancer screening outcomes among a referral population in Mexico. A cohort of 418 Mexican women aged 25 to 65, referred for colposcopy and biopsy due to abnormal cytology results (ASC-US+), participated in this study. Self-samples were analyzed using both the 14-type HPV DNA test and the 7-type HPV mRNA E6/E7 test. The study assessed the sensitivity, specificity, positive predictive value (PPV), and the necessity of colposcopies to detect CIN3+ lesions. Participant acceptability of self-sampling was also evaluated through a questionnaire. The 7-type HPV mRNA E6/E7 test demonstrated equivalent sensitivity but significantly higher specificity (77.0%) and PPV for CIN3+ detection compared to the 14-type HPV DNA test (specificity: 45.8%, p < 0.001). The use of the HPV mRNA test as a triage tool reduced the number of colposcopies needed per CIN3+ case detected from 16.6 to 7.6 (p < 0.001). Self-sampling was highly accepted among participants, with the majority reporting confidence in performing the procedure, minimal discomfort, and willingness to undertake self-sampling at home. Self-sampling combined with the 7-type HPV mRNA E6/E7 testing offers a promising strategy to enhance cervical cancer screening by improving accessibility and ensuring precise diagnostics. Implementing these app roaches could lead to a significant reduction in cervical cancer morbidity and mortality, especially in underserved populations. Future research should focus on the long-term impact of integrating these methods into national screening programs and explore the cost-effectiveness of widespread implementation.

Clinico-histopathological and molecular detection of small ruminants' papillomaviruses in Iran.

BACKGROUND: Papilloma DNA viruses are one of the viruses that cause skin lesions in ruminants. OBJECTIVES: The clinical, histopathological and molecular characteristics of cutaneous papilloma in ruminants in Iran are to be investigated in this study. METHODS: Samples were collected from 19 small ruminants (5 sheep and 14 goats) with various papillomatosis lesions. The samples taken were studied with histopathological and molecular techniques. RESULTS: In clinical terms, the lesions appeared in different sizes, ranging from 0.5 to 11 cm, and the cauliflower exophytic masses appeared in other parts of the animal's body. In the limbs, most papilloma lesions have been seen (42.1%). In histopathological examination, perinuclear vacuolation epidermal granule layer with various degrees of hypergranulosis, hyperkeratosis, acanthosis, orthokeratosis and parakeratosis were seen. Moreover, all the suspected samples were positive for papillomavirus using the polymerase chain reaction technique. CONCLUSIONS: Although the prevalence of papillomaviruses in Iranian sheep and goats is low, it seems necessary to distinguish them from other viral skin diseases, such as cutaneous contagious ecthyma, using molecular techniques and histopathology.

Meeting report: Considerations for trial design and endpoints in licensing therapeutic HPV16/18 vaccines to prevent cervical cancer.

Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come. The development and licensing of an affordable, accessible therapeutic HPV vaccine, designed to clear or control carcinogenic HPV and/or to induce regression precancer could significantly contribute to the elimination efforts, particularly benefiting those who missed out on the prophylactic vaccine. One barrier to development of such vaccines is clarity around the regulatory pathway for licensure. In Washington, D.C. on September 12-13, 2023, a meeting was convened to provide input and guidance on trial design with associated ethical and regulatory considerations. This report summarizes the discussion and conclusions from the meeting. Expert presentation topics included the current state of research, potential regulatory challenges, WHO preferred product characteristics, modeling results of impact of vaccine implementation, epidemiology and natural history of HPV infection, immune responses related to viral clearance and/or precancer regression including potential biomarkers, and ethical considerations. Panel discussions were held to explore specific trial design recommendations to support the licensure process for two vaccine indications: (1) treatment of prevalent HPV infection or (2) treatment of cervical precancers. Discussion covered inclusion/exclusion criteria, study endpoints, sample size and power, safety, study length, and additional data needed, which are reported here. Further research of HPV natural history is needed to address identified gaps in regulatory guidance, especially for therapeutic vaccines intended to treat existing HPV infections.

Whole-Transcriptome Sequencing-Based Profiling of the Cutaneous Virome in Patients with Secondary Immunodeficiency.

Most viral infections can be self-limited, with no requirement for medical intervention. However, the same viruses can cause severe diseases in patients with compromised immunity due to single-gene diseases, acquired immune deficiency syndrome, or hematologic malignancies or those receiving immunosuppressive drugs. Occasionally, these immunocompromised patients harbor >1 infectious agent, requiring several concomitant diagnostic tests. We have developed, to our knowledge, a previously unreported whole-transcriptome sequencing-based pipeline that allows virome profiling, quantitation, and expression pattern analysis of 926 distinct viruses by sequencing of RNA isolated from a single lesional skin biopsy. This pipeline can also explore host genetics if there is a Mendelian predisposition to infection. We applied this pipeline to 6 Iranian patients with viral-induced skin lesions associated with immune deficiency secondary to HIV, human T-lymphotropic virus 1, chronic lymphocytic leukemia, and post transplant immunosuppression. In 5 cases, definitive human papillomavirus infections were identified, some caused by multiple viral types. In addition to human papillomavirus, coinfection with other viruses (Merkle cell polyomavirus, cytomegalovirus, and human herpesvirus 4) was detected in some lesions. In 1 case, whole-transcriptome sequencing validated the clinical diagnosis of adult T-cell leukemia/lymphoma in a patient with an initial diagnosis of mycosis fungoides/Sézary syndrome. These findings attest to the power of whole-transcriptome sequencing in profiling the cutaneous virome in the context of compromised immunity.

Potential Transcript-Based Biomarkers Predicting Clinical Outcomes of HPV-Positive Head and Neck Squamous Cell Carcinoma Patients.

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.