Microfluid biosensor for detection of hpv in patient scraping samples: Determining E6 and E7 oncogenes.

E6 and E7 oncogenes are pivotal in the carcinogenic transformation in HPV infections and efficient diagnostic methods can ensure the detection and differentiation of HPV genotype. This study describes the development and validation of an electrochemical, label-free genosensor coupled with a microfluidic system for detecting the E6 and E7 oncogenes in cervical scraping samples. The nanostructuring employed was based on a cysteine and graphene quantum dots layer that provides functional groups, surface area, and interesting electrochemical properties. Biorecognition tests with cervical scraping samples showed differentiation in the voltammetric response. Low-risk HPV exhibited a lower biorecognition response, reflected in ΔI% values of 82.33 % ± 0.29 for HPV06 and 80.65 % ± 0.68 for HPV11 at a dilution of 1:100. Meanwhile, high-risk, HPV16 and HPV18, demonstrated ΔI% values of 96.65 % ± 1.27 and 93 % ± 0.026, respectively, at the same dilution. Therefore, the biorecognition intensity followed the order: HPV16 >HPV18 >HPV06 >HPV11. The limit of detection and the limit of quantification of E6E7 microfluidic LOC-Genosensor was 26 fM, and 79.6 fM. Consequently, the E6E7 biosensor is a valuable alternative for clinical HPV diagnosis, capable of detecting the potential for oncogenic progression even in the early stages of infection.

HPV16 Genomes: In Silico Analysis of E6 and E7 Oncoproteins in 20 South American Variants.

Background: Human papillomavirus (HPV) is the main risk factor for the development of squamous cell cervical cancer, and E6 oncoprotein and E7 oncoprotein are important components of the viral genome and its oncogenic potential. It is known that different viral variants of HPV16 have different pathology and impact on the development of neoplasia, although few studies have been performed on South American variants. Objective: Therefore, the present study aimed to analyze in silico the genomic diversity of HPV16 in 20 complete genome variants of South America in the National Center for Biotechnology Information (NCBI) database. Methods: We performed a descriptive study to characterize the polymorphic regions of the E6 and E7 genes in HPV16 variants, using software for genomic data and single nucleotide polymorphism (SNP) analysis and others for phylogenetic analysis. Results: The variants analyzed included six SNPs linked to cancer (A131G, G145T, C335T, T350G, C712A, and T732C) and significant variation (798 nucleotide substitutions). Despite this, the variants showed low genetic diversity. Eighteen variants of unclear significance (VUS) were identified, 10 of which were in the coding E6 regions and 8 in the coding E7 regions. The prevalence of lineage D variants is of concern due to their pathology in cervical cancer and requires more research and epidemiological vigilance regarding their prevalence in the population. Conclusion: The data obtained in this study may contribute to future research on South American variants of HPV16, their pathogenicity, and the development of treatments.

Prevalence of sexually transmitted infections and human papillomavirus in cervical samples from incarcerated women in São Paulo, Brazil: a retrospective single-center study.

Introduction: Sexually transmitted infections (STIs) cause considerable morbidity worldwide and, depending on the specific pathogen, may lead to serious complications in the female reproductive tract. Incarcerated women are particularly vulnerable to health problems with a disproportionate high rate of STIs, including infections with human papillomavirus (HPV). Methods: Here, cervical swab samples collected from 299 women (18 to 64 years) living in one of the women's prisons of São Paulo, Brazil were submitted for liquid-based cytology to determine the prevalence of precancerous lesions. Furthermore, direct detection of 30 genital HPV genotypes (18 high-risk and 12 low-risk types) and 11 additional STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus 1 and 2, Haemophilus ducreyi, Mycoplasma genitalium and hominis, Treponema pallidum, Trichomonas vaginalis, Ureaplasma parvum and urealyticum) were performed by molecular typing using two PCR-based DNA microarray systems, i.e., EUROArray HPV and EUROArray STI (EUROIMMUN), respectively. Results: The overall prevalence of cytological abnormalities was 5.8%, including five women with low-grade and five women with high-grade squamous intraepithelial lesions. The overall prevalence of HPV was 62.2, and 87.1% of the HPV-positive women were infected with oncogenic high-risk (HR) HPV types. HPV types 16 (24.1%), 33 and 52 (both 10.4%) were the most frequently detected. The prevalence of the other STIs was 72.8%. Up to four different pathogens were found in the infected women, the most frequent being Ureaplasma parvum (45.3%), Mycoplasma hominis (36.2%) and Trichomonas vaginalis (24.8%). Conclusion: The high number of HR-HPV infections and other STIs described here highlights the fact that the Brazilian female prison population requires more attention in the country's health policies. The implementation of screening programs and treatment measures might contribute to a decrease in the incidence of STIs and cervical cancer in this vulnerable population. However, for such measures to be effective, further studies are needed to investigate the best practice to get more women to engage in in-prison prevention programs, e.g., through offering further sexual health education and self-sampling.

Multifocal epithelial hyperplasia: an understudied infectious disease affecting ethnic groups. A mini review.

Focal Epithelial Hyperplasia or Multifocal Epithelial Hyperplasia (MEH), also known as Heck's disease, is considered a rare pathology of the oral mucosa associated with human papillomavirus types 13 and 32. For reasons not fully understood, MEH disproportionally affects specific populations of indigenous groups around the world. After the first reports in Native Americans, the epidemiology of the disease has been described in different geographical regions mainly related to particular indigenous populations, the majority of the studies are clinical case reports, but the biological determinants are still unknown. Some suggested risk factors include chronic irritation caused by smoking, a galvanic current, vitamin A deficiency, and/or a familial-genetic predisposition; however, the scientific evidence is not solid due the scarcity of case-control studies or longitudinal cohorts. In light of the evidence, further study of the pathology of MEH should be considered and proper clinical trials for effective treatments should be designed. The disease warrants further study as it is considered as neglected by research and it affects rural/remote population groups usually living in adverse socioeconomic conditions.

Challenges associated with follow-up care after implementation of an HPV screen-and-treat program with ablative therapy for cervical cancer prevention.

BACKGROUND: Cervical cancer is a preventable cancer; however, decreasing its prevalence requires early detection and treatment strategies that reduce rates of loss to follow-up. This study explores factors associated with loss to follow-up among HPV-positive women after implementation of a new HPV-based screen-and-treat approach for cervical cancer prevention in Iquitos, Peru. METHODS: We conducted semi-structured interviews with "obstetras" (i.e., midwives) (n = 15) working in cervical cancer prevention and women (n = 24) who were recorded as lost to follow-up after positive HPV results. We used the Health Care Access Barriers Model to guide analyses. We utilized manifest content analysis to describe barriers to follow-up according to the obstetras and thematic analysis to report themes from the women's perspectives. We also report the steps and time taken to contact women. RESULTS: We found an incomplete and fragmented patient monitoring system. This incomplete system, in conjunction with challenges in contacting some of the women, led to structural barriers for the obstetras when attempting to deliver positive results. Women in this study expressed a desire to receive treatment, however, faced cognitive barriers including a lack of understanding about HPV results and treatment procedures, fear or anxiety about HPV or treatment, and confusion about the follow-up process. Women also reported having important work matters as a barrier and reported frequently using natural medicine. Reported financial barriers were minimal. CONCLUSION: This study highlights the barriers to follow-up after implementation of a primary-level HPV-based screen-and-treat approach. While some barriers that have previously been associated with loss to follow-up were not as prominently observed in this study (e.g., financial), we emphasize the need for screen-and-treat programs to focus on strategies that can address incomplete registry systems, structural challenges in results delivery, cognitive barriers in understanding results and treatment, and work-related barriers.

Acquired epidermodysplasia verruciformis syndrome in HIV-infected patients: a systematic review.

Congenital epidermodysplasia verruciformis (CEV) is a Genodermatosis linked to different inheritance patterns and mutations of the EVER1/TMC6 and EVER2/TMC8 genes. There is an acquired form (AEV) associated with immunodeficiency states, including human immunodeficiency virus (HIV) infection; however, the literature about AEV is limited and imprecise, so a systematic review was performed. A search of the main databases from 1975 to 2021 identified 126 studies, of which 80 met the inclusion criteria. The diagnosis of AEV is complex due to atypical manifestations and locations, it requires a mean follow-up of 7 years, and the lesions do not change with ART therapy, CD4 count, or viral load. Histopathological findings are variable depending on the location of the lesions. HPV 5 remains the serotype most frequently associated with AEV and CEV, although HPV 20 is more frequent than HPV 8 in AEV. Most treatments have low efficacy, the most described are glycolic acid 15%, 5-fluorouracil 5%, imiquimod 5%, and topical retinoids all of them in monotherapy or combined with cryotherapy. Other alternatives include topical cidofovir and systemic retinoids with variable results. The oncologic prognosis is still inconclusive; however, the development of squamous cell carcinoma and melanoma are frankly lower concerning CEV. This review opens new opportunities for future research. Additionally, we provide clear and useful key points for the practice of dermatologists and all professionals treating HIV patients around the world.

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

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

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.

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.

Association of body mass index with anal human papillomavirus infection and histologically confirmed high-grade squamous intraepithelial lesions in people who receive services at the Anal Neoplasia Clinic in Puerto Rico.

Objective: This study aimed to assess the association of body mass index (BMI) with anal high-risk human papillomavirus (HR-HPV) and biopsy-confirmed histologic anal high-grade squamous intraepithelial lesions (HSIL) among a clinic-based sample of Hispanics in Puerto Rico. Methods: This cross-sectional study evaluated medical records of adults who received services at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center between October 2014 and December 2022. The study included 543 records with complete clinical information regarding anal HR-HPV and anal HSIL status. Chi-square and logistic regression analyses were performed. Results: Mean age of participants was 44.10 ± 13.24 years, 65.2% were men, 71.7% were HIV-infected, 74.4% had anal HR-HPV infection, and 37.9% had biopsy-confirmed HSIL. Regarding BMI, 2.4% were underweight, 31.9% normal weight, and 39.0 % overweight; while 17.3 % had class I, 5.2% class II, and 4.2% class III obesity. No significant association was observed between BMI and anal HR-HPV infection in adjusted analyses. Lower odds of anal HSIL were observed among overweight individuals (OR: 0.63, 95% CI: 0.41 - 0.99) and those with class II/III obesity (OR: 0.48, 95% CI: 0.22 - 1.01) compared to adults with underweight/normal BMI, after adjusting for potential confounders. No significant association was observed for class I obesity. Conclusion: BMI was not associated with anal HR-HPV infection. Overweight and obese individuals had lower odds of having anal HSIL than adults with underweight/normal BMI. This finding could suggest underdiagnosis of HSIL among overweight/obese individuals, or reduced risk in this group.

Gingivectomy-Gingivoplasty for Oral Physiological Melanosis Depigmentation: A Case Report Involving Human Papillomavirus.

Gingiva hyperpigmentation resulting from physiological melanosis causes aesthetic discomfort and is usually perceived as a disease by patients because healthy attached gingiva is typically characterized by coral pink coloring with stippling and scalloped contours. When physiological melanosis compromises the aesthetics of smiling, it may induce insecurity in patients, who usually seek out alternatives for reducing or eliminating hyperpigmentation. We present a case report of a surgical procedure combining gingivectomy with gingivoplasty for the management of physiological melanosis. The surgical procedure was performed on a 40-year-old female patient with bilateral pigmentation in both arches. The results of the histological analysis confirm the diagnoses of melanotic macula, with papillary hyperplasia and cytopathic changes being suggestive of HPV infection, which was verified using an immunohistochemistry analysis based on the detection of a major capsid protein of HPV. Acceptable functional and aesthetic results were obtained for the patient without major discomfort during the postoperative period. In cases when HPV infection is present, long-term follow-up becomes necessary.

Cationic Liposomes Carrying HPV16 E6-siRNA Inhibit the Proliferation, Migration, and Invasion of Cervical Cancer Cells.

The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.

Stakeholders' Perceptions on the Implementation of the HPV Vaccine School-Entry Requirement in Puerto Rico during the COVID-19 Pandemic.

This study explored the implementation of the human papillomavirus (HPV) vaccine school-entry requirement in Puerto Rico during the COVID-19 pandemic. We conducted 26 semi-structured interviews with stakeholders and community-based organizations from August 2021 to March 2022. The interview guide was developed using the 2009 Consolidated Framework for Implementation Research (CFIR). The interviews were recorded and transcribed in Spanish. Data were analyzed using applied thematic techniques. These themes included the following: (i) Intervention characteristics: Participants noted that the school-entry requirement was effective in increasing vaccination uptake prior to the pandemic. Issues with the immunization registry were noted; (ii) Outer setting: External influences, access barriers, and an increase in HPV vaccine exemptions since the implementation of the COVID-19 vaccine were discussed; (iii) Inner setting: Communication within organizations and HPV vaccination efforts improved as the pandemic progressed; (iv) Characteristics of individuals: Most agreed with the school-entry requirement, including exemptions; and (v) Process: Results showed the need to reinforce the population's education about HPV and the vaccine. Implementation of the policy was challenging during the early stages of the pandemic due to measures enacted to stop the spread of COVID-19 and focus on the COVID-19 vaccine. Efforts to increase HPV vaccine should focus on increasing HPV vaccine education and creating collaborations.

HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.

Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

Academic accountability to local communities and society through Programme Science: a case study from the HPV self-sampling programme HOPE in Peru.

INTRODUCTION: Health challenges in the 21st century underscore the need for adaptable and innovative approaches in public health. Academic institutions can and should contribute much more effectively to generate and translate scientific knowledge that will result in better programmes to improve societal health. Academic accountability to local communities and society requires universities to actively engage with local communities, understanding the context, their needs, and leveraging their knowledge and local experience. The Programme Science initiative provides a framework to optimize the scale, quality and impact of public health programmes, by integrating diverse approaches during the iterative cycle of research and practice within the strategic planning, programme implementation and programme management and evaluation. We illustrate how the Programme Science framework could be a useful tool for academic institutions to accomplish accountability to local communities and society through the experience of Project HOPE in Peru. DISCUSSION: Project HOPE applied the Programme Science framework to introduce HPV self-sampling into a women's health programme in Peru. Collaboration with local authorities and community members was pivotal in all phases of the project, ensuring interventions aligned with community needs and addressing social determinants of health. The HOPE Ladies-community women trained and empowered to promote and provide the HPV kits-crafted the messages used through the study and developed strategies to reach individuals and provided support to women's journey through health centres. By engaging communities in co-creating knowledge and addressing health inequities, academic institutions can generate contextually relevant and socially just scientific knowledge. The active participation of community women in Project HOPE was instrumental in improving service utilization and addressing barriers to self-sampling. CONCLUSIONS: The Programme Science approach offers a pathway for academic institutions to enhance their accountability to communities and society at large. By embedding researchers within public health programmes and prioritizing community engagement, academic institutions can ensure that research findings directly inform policy improvements and programmatic decisions. However, achieving this requires a realignment of research agendas and recognition of the value of community engagement. Establishing Programme Science networks involving academia, government and funding entities can further reinforce academic accountability and enhance the impact of public health programmes.

Pap test recency and HPV vaccination among Brazilian immigrant women in the United States: a cross-sectional study.

BACKGROUND: The United States (U.S.) has a growing population of Brazilian immigrant women. However, limited research has explored Pap tests and human papillomavirus (HPV) vaccination among this population. METHODS: Participants completed an online survey between July-August 2020. Bivariate analyses examined associations between healthcare-related variables (e.g., insurance, having a primary care provider) and demographics (e.g., age, education, income, marital status, years living in the U.S., primary language spoken at home) with 1) Pap test recency (within the past 3 years) and 2) HPV vaccination (0 doses vs. 1 + doses). Variables significant at p < 0.10 in bivariate analyses were included in multivariable logistic regression models examining Pap test recency and HPV vaccination. RESULTS: The study found that 83.7% of the sample had a Pap test in the past three years. Women who did not know their household income were less likely to be than women who reported a household income of < $25,000 (adjusted OR [aOR] = 0.34, 95% CI: 0.12, 0.95). Women who had seen a healthcare provider in the past year were more likely to have had a Pap test within the last three years than those who had not seen a provider in the past year ([aOR] = 2.43, 95% CI: 1.32, 4.47). Regarding HPV vaccination, 30.3% of respondents reported receiving one or more doses of the HPV vaccine. The multivariable logic regression models determined that women aged 27 -45 (aOR = 0.35, 95% CI: 0.18, 0.67) were less likely than women aged 18-26 to have been vaccinated against HPV). and that women with a PCP were more likely to be vaccinated than those without a PCP (aOR = 2.47. 95% CI:1.30, 4.59). CONCLUSION: This study found that Brazilian immigrant women in the youngest age groups (21 - 29) for Pap test, 18- 26 for HPV vaccination) had somewhat better rates of Pap screening and HPV vaccination than the general U.S. POPULATION: This study adds new information about cervical cancer prevention and control behaviors among Brazilian immigrant women.

Anal cancer risk and HPV infection knowledge and awareness among Hispanic persons living with HIV in Puerto Rico.

Background: Persons living with HIV (PLWH) have a higher risk of persistent infection with human papillomavirus (HPV) and anal cancer. We evaluated knowledge and awareness of HPV infection and risk factors for anal cancer among PLWH in Puerto Rico (PR). Methods: Data from a cross-sectional study (2020-2021) were analyzed (n=212). Inclusion criteria included PLWH, aged ≥ 26 years, and living in PR. Telephone interviews collected information on sociodemographic, lifestyle and clinical characteristics. Two 13-item scales were used to assess knowledge of HPV and anal cancer risk factors; adequate knowledge for both scales were defined as scoring >70%. Logistic regression models using generalized linear models were used to determine the association between 1) HPV infection awareness, 2) HPV infection knowledge, and 3) Anal cancer risk factors knowledge. Results: The median age was 54 years (IQR: 46,58), 67.5% were male, 71.7% reported having an income <$20,000, and 54.3% had an education level of more than high school. HPV awareness was high (82.1%), but only 40.2% and 3.8% had adequate knowledge of HPV and anal cancer risk factors, respectively. In adjusted logistic regression models, men who have sex with men (OR: 1.26, 95%CI: 1.07-1.47) and women (OR: 1.35, 95%CI: 1.15-1.59) aged ≥50 years had higher odds of HPV awareness than heterosexual men in that age group. Moreover, those with history of anal Pap test aged <50 years had more HPV awareness (OR 1.34, 95%CI: 1.08-1.66) than their counterparts. Adequate HPV knowledge was higher among participants with an education level of more than high-school (OR:1.28, 95%CI: 1.10-1.50) and with a history of HPV diagnosis (OR:1.33, 95%CI: 1.08-1.65) than their counterparts. In addition, people with good/very good/excellent health perception had higher odds of HPV knowledge (OR:1.23, 95%CI: 1.03-1.47) than those who reported poor/regular health perception. For anal cancer risk factors, PLWH for ≥15 years had increased odds of having adequate knowledge (OR:1.07, 95%CI: 1.02-1.14) than their counterparts. Conclusions: Despite high awareness of HPV, limited knowledge about HPV and anal cancer risk factors was observed among PLWH. Results from our study highlight the need for educational efforts within this population as an anal cancer prevention strategy.

Identification and Functional Implications of the E5 Oncogene Polymorphisms of Human Papillomavirus Type 16.

The persistence of the human papillomavirus type 16 (HPV16) infection on the cervical epithelium contributes to the progression of cervical cancer. Studies have demonstrated that HPV16 genetic variants may be associated with different risks of developing cervical cancer. However, the E5 oncoprotein of HPV16, which is related to several cellular mechanisms in the initial phases of the infection and thus contributes to carcinogenesis, is still little studied. Here we investigate the HPV16 E5 oncogene variants to assess the effects of different mutations on the biological function of the E5 protein. We detected and analyzed the HPV16 E5 oncogene polymorphisms and their phylogenetic relationships. After that, we proposed a tertiary structure analysis of the protein variants, preferential codon usage, and functional activity of the HPV16 E5 protein. Intra-type variants were grouped in the lineages A and D using in silico analysis. The mutations in E5 were located in the T-cell epitopes region. We therefore analyzed the interference of the HPV16 E5 protein in the NF-kB pathway. Our results showed that the variants HPV16E5_49PE and HPV16E5_85PE did not increase the potential of the pathway activation capacity. This study provides additional knowledge about the mechanisms of dispersion of the HPV16 E5 variants, providing evidence that these variants may be relevant to the modulation of the NF-κB signaling pathway.

Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis.

Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1ß to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus.

P53 and pRB induction improves response to radiation therapy in HPV-positive laryngeal squamous cell carcinoma.

INTRODUCTION: Patients with Human Papillomavirus (HPV+)-associated Laryngeal Squamous Cell Carcinoma (LSCC) exhibit dramatically improved survival relative to those with HPV-Negative (HPV-) tumors. In this study, the authors aimed to investigate the radiosensitivity of all available confirmed HPV+ and HPV-LSCC cells in vitro and in vivo. METHODS: Primary LSCC cells were generated from tumor specimens obtained from patients. Real-time PCR was performed to confirm HPV infection and the expression of HPV-related genes (E6 and E7), p53, and pRB. Clonogenic survival assays, western blotting, and flow cytometry were used to assess radiation sensitivity, apoptosis, and the expression of p53 and pRB. p53 and pRB knockout cells were generated using CRISPR/Cas9 technology. RESULTS: HPV+ LSCC cells displayed enhanced radiation sensitivity compared to HPV- cells. Radiation-induced apoptosis in HPV+ LSCC cells, accompanied by increased levels of p53 and pRB. Knockout of p53 or pRB led to radiation resistance and attenuated radiation-induced apoptosis in HPV+ LSCC cells. In vivo experiments showed similar results, where knockout of p53 or pRB decreased radiosensitivity in tumor-bearing mice. CONCLUSION: The present findings demonstrated that HPV+ LSCC cells displayed obvious inherent radiation sensitivity, corresponding to increased apoptosis following radiation exposure. Mechanism study showed that the expression of p53 and pRB in HPV+ cells are required for radiation sensitivity. These findings highlight a novel mechanism by which p53 and pRB play key roles in the radiation sensitivity of HPV+ LSCC compared to HPV-LSCC.