Search Results (2,419)

Background: Human Papillomavirus (HPV) is the primary cause of cervical cancer. Single-dose HPV vaccination can effectively prevent high-risk HPV infection that causes cervical cancer and accelerate progress toward achieving cervical cancer elimination goals. We modelled the potential impact of adopting single-dose HPV vaccination strategies on health and economic outcomes in Kenya, where a two-dose schedule is the current standard. Methods: Using a validated compartmental transmission model of HPV and HIV in Kenya, we evaluated the costs from the payer’s perspective to vaccinate girls by age 10 with either one or two doses and increasing coverage levels (0%, 70%, 77%, 90%). Additionally, we modelled single-dose strategies supplemented with either catch-up vaccination of adolescent girls and young women or vaccination for all by age 10, funded with the first five-years of cost savings of switching from a two- to one-dose schedule. Costs and outcomes were discounted at 3% annually, and incremental cost-effectiveness ratios (ICERs) were calculated per disability-adjusted-life-year (DALY) averted. Results: All one-dose and the two-dose 90% coverage strategies were on the efficiency frontier, dominating the remaining two-dose strategies. The two-dose 90% coverage strategy had a substantially higher ICER (US$6508.80/DALY averted) than the one-dose 90% coverage (US$197.44/DALY averted). Transitioning from a two- to one-dose schedule could result in US$21.4 Million saved over the first five years, which could potentially fund 2.75 million supplemental HPV vaccinations. With this re-investment, all two-dose HPV vaccination scenarios would be dominated. The greatest DALYs were averted with the single-dose HPV vaccination schedule at 90% coverage supplemented with catch-up for 11–24-year-old girls, which had an ICER of US$78.73/DALYs averted. Conclusion: Considering the logistical and cost burdens of a two-dose schedule, a one-dose schedule for girls by age 10 would generate savings that could be leveraged for catch-up vaccination for older girls and accelerate cervical cancer elimination in Kenya. Full article

The host transcription factor p53 is a critical tumor suppressor in HPV-induced carcinogenesis, regulating target genes involved in cell cycle arrest and apoptosis. However, the p53 targets have not been thoroughly analyzed in HPV-infected cells. In this study, p53 signaling in HPV16 and HPV18 cells was activated by depleting the viral oncoprotein E6. Subsequently, p53-regulated genes were identified by comparing them with genes altered in p53-silenced cells. True p53 targets were defined as genes with at least one overlapping p53 binding site and ChIP peak near their locus. Our analysis revealed that while some p53 targets were common to both the HPV16 and HPV18 cells, the majority of the targets differed between these two types, potentially contributing to the varying prevalence of HPV16 and HPV18 in cervical cancer. Additionally, we identified SCN2A as a novel p53 target involved in p53-induced cell cycle arrest in HPV-related carcinogenesis. This study provides new insights into the mechanisms by which p53 inhibits HPV-induced carcinogenesis. Full article

Background/Objectives: Given the discrepancies in immunisation coverage, the goal of this study was to explore the barriers and facilitators to effective communication across the school-based vaccination program in South Eastern Sydney schools. Methods: A qualitative study was undertaken with purposively selected immunisation staff, school coordinators, and parents of Year 7 students who had not received two vaccinations (dTpa and HPV) at school. A focus group with immunisation staff and interviews with school coordinators explored the barriers and facilitators to vaccination uptake, including communication across stakeholders. The parent interviews explored attitudes to vaccination and the school program and investigated the program communication methods. Results: Five immunisation staff, eleven school coordinators, and eleven parents participated in the study. The barriers to participation in the school vaccination program included low parent recall of vaccination information, challenges encountered by school staff in consent tracking, no communication channel between health staff and parents, a greater school focus on vaccination facilitation than student education, and limited communication between stakeholders about catch-up vaccinations. The facilitators included established school/parent relationships for vaccine communication, effective communication between health and school staff, and using multiple methods to promote clinic and consent requirements. Conclusions: Opportunities exist to increase program participation by enhancing vaccination information and education for students and parents, with better communication about vaccination catch-ups and consent. Full article

Background: Current L1-based human papillomavirus (HPV) vaccines provide type-specific protection but offer limited cross-protection against non-vaccine HPV types. Therefore, developing a broad-spectrum HPV vaccine is highly desirable. Methods: In this study, we optimized mRNA constructs and developed a multivalent L2-based mRNA vaccine encoding L2 aa 2-130, which includes all known neutralizing epitopes from four prevalent HPV types (HPV-6, -11, -16, and -18). We evaluated its immunogenicity in a mouse model and compared the efficacy of a commercially available mRNA delivery reagent with a custom-synthesized lipid nanoparticle (LNP) formulation. Results: We identified that a construct containing E01 (a 5′-untranslated region) and SL2.7 (a poly(A) polymerase recruitment sequence) significantly increased protein expression. The L2-based mRNA vaccine induced robust and long-lasting humoral immune responses, with significant titers of cross-reactive serum IgG antibodies against L2 epitopes. Notably, the vaccine elicited cross-neutralizing antibodies and conferred cross-protective immunity not only against vaccine-targeted HPV types but also against non-vaccine HPV types, following intravaginal challenge in mice. We also found that LNP delivered mRNA more effectively in vivo. Conclusions: The L2-based mRNA vaccine developed in this study shows significant potential for broad-spectrum protection against multiple HPV types. This approach offers a promising strategy for reducing the global burden of HPV-associated cancers. Full article

Cervical cancer remains a significant global health concern, particularly in low- and middle-income countries. While persistent infection with high-risk human papillomavirus (HR-HPV) is essential for cervical cancer development, it is not sufficient on its own, suggesting the involvement of additional cofactors. The human cytomegalovirus (HCMV) is a widespread β-herpesvirus known for its ability to establish lifelong latency and reactivate under certain conditions, often contributing to chronic inflammation and immune modulation. Emerging evidence suggests that HCMV may play a role in various cancers, including cervical cancer, through its potential to influence oncogenic pathways and disrupt host immune responses. This review explores clinical evidence regarding the co-presence of HR-HPV and HCMV in premalignant lesions and cervical cancer. The literature reviewed indicates that HCMV is frequently detected in cervical lesions, particularly in those co-infected with HPV, suggesting a potential synergistic interaction that could enhance HPV’s oncogenic effects, thereby facilitating the progression from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) and invasive cancer. Although the precise molecular mechanisms were not thoroughly investigated in this review, the clinical evidence suggests the importance of considering HCMV alongside HPV in the management of cervical lesions. A better understanding of the interaction between HR-HPV and HCMV may lead to improved diagnostic, therapeutic, and preventive strategies for cervical cancer. Full article

Background: The increasing trend of cervical cancer in women in their 20s in Japan is largely attributable to the low rate of cervical cancer screening. This study aimed to assess the usefulness of human papillomavirus (HPV) self-sampling among 24-year-old Japanese women who had never previously been screened for cervical cancer during the coronavirus disease (COVID-19) pandemic. Methods: In August 2021, consenting eligible women received HPV self-sampling kits. An Evalyn brush was used for self-sampling, and a Cobas 4800 PCR-based HPV DNA test was used to detect high-risk HPV genotypes. We analyzed the return rates of self-sampling kits and conducted a survey on the acceptability of the self-sampling method. Results: Of the total 1997 eligible women, 13.4% (268/1997) agreed to participate. The return rate of the kits was 72.4% (194/268), corresponding to 9.7% of the eligible population. Among the participants who returned the kits, 14.9% (29/194) tested positive for HPV, and 41.4% (12/29) of these underwent subsequent cytological testing. The questionnaire results indicated that 57.8% of participants reported no pain during self-sampling, and 72.9% expressed a willingness to continue using the self-sampling method in the future. Conclusion: This study demonstrated that opt-in HPV self-sampling among 24-year-old women who had never been screened for cervical cancer had a favorable kit return rate and was well accepted by the participants, especially during the COVID-19 pandemic. However, the follow-up cytology test rates were low, highlighting the need for improved post-screening management. Full article

Avoidance of an immune response is critical to completion of the human papillomavirus (HPV) life cycle, which occurs in the stratified epithelium and is linked to epithelial differentiation. We previously demonstrated that high-risk HPVs use apoptotic caspases to suppress an antiviral innate immune response during the productive phase of the life cycle. We found that caspase-8 and caspase-3 suppress a type I IFN-β and type III IFN-λ response by disabling the MDA5/MAVS double-stranded RNA (dsRNA) sensing pathway, indicating that immunogenic RNAs increase upon differentiation in HPV+ cells. In this study, we demonstrate that caspase inhibition results in aberrant transcription of a subset of endogenous retroviruses (ERVs) that have been shown to activate an IFN response through dsRNA-sensing pathways. We show that the increase in ERV transcription is accompanied by an enrichment in dsRNA formation. Additionally, we demonstrate that the robust increase in ERV expression requires activation of the JAK/STAT-signaling pathway, indicating that this subset of ERVs is IFN-inducible. Overall, these results suggest a model by which caspase activity blocks the reactivation of ERVs through the JAK/STAT pathway, protecting HPV+ cells from an increase in immunogenic dsRNAs that otherwise would trigger an IFN response that inhibits productive viral replication. Full article

Background: Cervical cancer, predominantly caused by human papillomavirus, remains a major public health issue globally and in Kazakhstan, where it ranks among the most common cancers in women. A pilot HPV vaccination programme in Kazakhstan was suspended in 2017 due to mass parental refusals, and it is planned to be restarted in the coming years. This study aims to assess the knowledge, attitudes, barriers, and sources of information about HPV and the HPV vaccine among healthcare professionals in Kazakhstan. Methods: A cross-sectional study (December 2022–May 2023) involving 1189 healthcare professionals in Kazakhstan used a self-administered questionnaire. Statistical analysis included descriptive statistics, mean knowledge score, between-group comparisons, and binary logistic regression to identify factors linked to higher knowledge and vaccine recommendation. Results: The study found that the average knowledge score for HPV and the HPV vaccine among participants was 11 out of a possible 18. Correct answers to the questionnaire were observed more frequently among physicians than among nurses (p < 0.001). In our study, 72.6% of healthcare professionals expressed a positive intention to recommend the HPV vaccine. The likelihood of recommending the HPV vaccine was significantly higher among those with higher knowledge of HPV and its vaccine (OR 1.8; 95% CI 1.3–2.5; p < 0.001), those familiar with cervical cancer patients (OR 2.0; 95% CI 1.5–2.8; p < 0.001), and those with positive attitudes towards the COVID-19 vaccine and childhood vaccination (OR 2.3 and 1.5, respectively). Healthcare professionals identified key barriers to HPV vaccination, including public mistrust (49.4%), fear of side effects (45.9%), and insufficient knowledge among healthcare professionals themselves (30.3%). Information from the internet, including articles and journals, was the most commonly used source of information, followed by social media and colleagues. Conclusions: The disparities identified call for a tailored, multifaceted communication strategy that addresses the diverse needs of health professionals to address the differences in awareness between different groups, in order to ensure successful implementation and coverage of HPV vaccination across Kazakhstan. Full article

Background/Objectives: Human papillomavirus (HPV) is a causative agent of infections and cancers of the reproductive and digestive tract, and vaccination is the most effective prevention method. This research aimed to assess the impact of health education on vaccination coverage and knowledge of the school population related to HPV infection and vaccination. Methods: This non-randomized clinical trial included 170 participants out of the 221 students in the generation of 2022/2023, who were divided into a group of Subjects and Controls and who self-assessed their knowledge and tested knowledge at four and two time points, respectively. Results: The study examined whether there is a difference in the share of vaccinated students of the entire generation compared to the previous generation (62% vs. 47%). The self-assessment and assessment of one’s knowledge in the group of subjects was significantly lower before education than during other time points during the research. At “moment zero”, there was no significant difference in the knowledge assessment between the groups. However, after 8 weeks, the knowledge assessment was significantly higher in the Subject group. Conclusions: The results suggest a positive impact of health education, which may contribute to raising awareness about the importance of prevention and vaccination against HPV. Full article

Antiretroviral therapy (ART) has significantly extended the lifespan of people living with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), thereby transforming the disease into a manageable chronic condition. However, this increased longevity has led to a higher incidence of non-AIDS-defining cancers (NADCs) among this population. In this holistic review, we explore the complex interactions between HIV, ART, and cancer development, focusing on how ART influences tumor initiation and progression in people living with HIV/AIDS (PLWHA). Our findings from this reveal several critical aspects of cancer risk in PLWHA. Firstly, while ART restores immune function, it does not fully normalize it. Chronic immune activation and persistent inflammation continue to be prevalent, creating a conducive environment for oncogenesis. Additionally, PLWHA are more susceptible to persistent infections with oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV), further increasing cancer risk. Some ART drugs have been implicated in genotoxicity and mitochondrial dysfunction, potentially promoting tumorigenesis. ART-induced metabolic changes, including insulin resistance and dyslipidemia, are also associated with heightened cancer risk. Common NADCs in PLWHA include lung cancer, liver cancer, anal cancer, and Hodgkin lymphoma, each with distinct etiologies linked to both HIV-related and ART-related factors. The interplay between HIV infection, chronic inflammation, immune restoration via ART, and the direct effects of ART drugs creates a unique cancer risk profile in PLWHA. Although ART reduces the incidence of AIDS-defining cancers, it does not confer the same protective effect against NADCs. Persistent HIV-related inflammation and immune activation, despite viral suppression, are key factors in cancer development. Additionally, long-term exposure to ART may introduce new oncogenic risks. These insights highlight the need for integrated cancer screening and prevention strategies tailored to PLWHA. Future research is needed to focus on identifying biomarkers for early cancer detection and developing ART regimens with lower oncogenic potential. Healthcare providers should be vigilant in monitoring PLWHA for cancer and adopt comprehensive screening protocols to mitigate the increased cancer risk associated with ART. Full article

Objectives: This study used multilevel social determinants of health (SDoH) models to determine how SDoH influence different sexes of patients diagnosed with HPV-positive oropharyngeal squamous cell cancers (OPSCC) across the US. Methods: This was a retrospective cohort study assessing HPV-confirmed patients with oropharyngeal squamous cell cancers from 2010 to 2018 using census-level Yost Index socioeconomic status (SES) score and rurality–urbanicity measures alongside individual-level race–ethnicity while stratifying by biological sex. Age-adjusted multivariate regressions were performed for survival, treatment receipt, and delay of treatment initiation (of 3+ months). Results: Across 14,076 OPSCC-HPV-positive patients, delay of treatment uniquely featured positive predictors for males of black race–ethnicity (OR, 2.07; 95% CI, 1.68–2.54) and poor Yost SES (1.43; 1.24–1.65). Five-year all-cause mortality uniquely showed positive predictors of females of black race–ethnicity (2.74; 1.84–4.71) and of males with poor Yost SES (1.98; 1.79–2.19). Three-year all-cause mortality shared positive predictors across sexes but were exacerbated in females of black race–ethnicity (2.50; 1.82–3.44) compared to males (2.23; 1.91–2.60); this was reversed for poor Yost SES (male, 1.92, 1.76–2.10; female, 1.60, 1.32–1.95). Surgery showed negative predictors of black race–ethnicity that displayed worsened effects in females (0.60, 0.44–0.79) versus males (0.75, 0.66–0.86). First-line radiation receipt uniquely featured negative predictors for males of black race–ethnicity (0.73; 0.62–0.86) with poor Yost SES (0.74; 0.68–0.82). Conclusions: Comprehensive models of multilevel SDoH displayed exacerbated disparity effects of community-level SES in males and black race–ethnicity among female HPV-positive OPSCC patients. These objective comparisons of specific SDoH factors inform providers and policy direction on how to strategically target the most pertinent SDoH factors affecting a rapidly growing cancer population. Full article

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. In addition to known risk factors, oncoviruses have attracted exceptional attention from recent research. Numerous hypotheses on interactions between the Epstein–Barr virus (EBV) and Human papillomavirus (HPV) in CRC are still based on sparse prevalence data of these coinfections. The aim of this study was to perform a comprehensive literature search regarding EBV/HPV coinfection in patients with CRC and to provide its prevalence in the target population. Three electronic databases (PubMed, SCOPUS, and WoS) were searched, and after a double reviewer check, six publications were included in the qualitative and quantitative analyses. This systematic review showed the limited number of studies dealing with the prevalence and role of EBV/HPV coinfection in CRC and the heterogeneity of methodology and reported results. However, in a total of 635 patients, it also showed that the identified 15% EBV/HPV prevalence in CRC (15%, 95% CI: 7–23%) could suggest that further investigations are needed. Histopathologically, all coinfected CRCs were adenocarcinomas, from intermediate to intermediate and high grade, reported across four studies. Increased knowledge about the infectious origin of various cancers, including CRC, has the potential to enhance the vigilance of scientists to design future large-scale multicenter prospective studies. Full article

Cervical cancer is a largely preventable malignancy of the uterine cervix. The tendencies in cervical cancer morbidity and mortality have remained similar for the past decade, albeit with increasing frequency in low- and middle-income countries (LMICs). Moreover, in the majority of LMICs, cervical cancer is the second most prevalent cancer and the second most common cause of cancer-related death among reproductive-age women. High-risk human papillomavirus (HR-HPV) infections have been proven to be associated with up to 95% of cervical cancer cases, with HPV-16 and HPV-18 types being responsible for approximately 70% of all cervical cancers, with the other high-risk HPV types accounting for up to a further 25%. More recently, the latest data appear to confirm there is a change in the frequency of HR-HPV occurrence, especially HPV-16 and HPV-18, as a reflection of the implementation of preventive vaccination programs. Owing to the growing incidence of cervical cancer among reproductive-age women and with the development of cancer management approaches, fertility-sparing options have been proposed for early-stage cervical cancer management as an option for young women, especially those with unaccomplished reproductive desires. However, methods applied for this purpose (cold-knife conization, loop electrosurgical excision, trachelectomy) have variable outcomes and do not prevent risks of relapse. Multiple factors are involved in cervical cancer recurrence, even in cases treated at the early stage of the disease. In this review, the authors unveil whether HPV infection and virus type could be one of the key factors associated with cervical cancer recurrence after fertility-sparing surgery. Reviews of the literature reveal that recurrent and persistent HR-HPV infection is a strong predictor of cervical lesions’ relapse. In particular, HPV-16 and HPV-18 infections and their persistence have been reported to be associated with cervical cancer recurrence. HR-HPV genotyping before and after fertility-sparing surgery for cervical cancer could facilitate a personalized approach and improve the overall survival rate. Screening for HR-HPV is essential during the follow-up of cervical cancer-treated women and will help to predict possible cancer recurrence. Full article

Background: Human papilloma virus (HPV) infection is responsible for 4.5% of cancers worldwide, i.e., for around 630,000 new cases per year. Around 38,000 cases per year of HPV-related cancers arise in the head and neck region, of which 21,000 cases are oropharyngeal squamous cell carcinomas (OPSCCs), with an increasing frequency in high-income countries. In our work, we aimed to collect the available evidence about the awareness of the relation between HPV infection and head and neck cancer among patients and practitioners. Methods: This review was based on all available prospective and retrospective studies, case reports, and review articles published up to May 2024 in PubMed. The search keywords used included “human papilloma virus” plus “head and neck cancer”, “awareness”, “infection”, “vaccination”, “awareness in patients and practitioners”, “oropharyngeal squamous cell carcinoma”, “HPV16-18”, “HPV awareness”, “cervical cancer”. Results: In the U.S.A., with more than 150.00 participants interviewed through different studies, the identification of HPV infection as a risk factor for head and neck cancer (HNC) was made by only 12–39% of the participants. Similar conclusions were drawn from European studies in which only 10–52% of the participants recognized HPV as a risk factor for HNC. HPV-related HNC awareness in health care providers and medical/dental students showed a high variability among studies, being otolaryngology and dental sciences specialists the most conscious in comparison to general practitioners, who demonstrated a low level of awareness. Conclusions: There is a dangerous lack of awareness about HPV infection and its potential role in HNC among both general populations and health care practitioners. A great effort should be made to increase awareness in both practitioners and the general population on this topic, also aiming to increase the HPV vaccination coverage. Full article

Background/Objectives: While human papillomavirus (HPV) is well known for its role in cervical cancer, it also affects vaginal cancers. Although colposcopy offers a comprehensive examination of the female genital tract, its diagnostic accuracy remains suboptimal. Integrating artificial intelligence (AI) could enhance the cost-effectiveness of colposcopy, but no AI models specifically differentiate low-grade (LSILs) and high-grade (HSILs) squamous intraepithelial lesions in the vagina. This study aims to develop and validate an AI model for the differentiation of HPV-associated dysplastic lesions in this region. Methods: A convolutional neural network (CNN) model was developed to differentiate HSILs from LSILs in vaginoscopy (during colposcopy) still images. The AI model was developed on a dataset of 57,250 frames (90% training/validation [including a 5-fold cross-validation] and 10% testing) obtained from 71 procedures. The model was evaluated based on its sensitivity, specificity, accuracy and area under the receiver operating curve (AUROC). Results: For HSIL/LSIL differentiation in the vagina, during the training/validation phase, the CNN demonstrated a mean sensitivity, specificity and accuracy of 98.7% (IC95% 96.7–100.0%), 99.1% (IC95% 98.1–100.0%), and 98.9% (IC95% 97.9–99.8%), respectively. The mean AUROC was 0.990 ± 0.004. During testing phase, the sensitivity was 99.6% and 99.7% for both specificity and accuracy. Conclusions: This is the first globally developed AI model capable of HSIL/LSIL differentiation in the vaginal region, demonstrating high and robust performance metrics. Its effective application paves the way for AI-powered colposcopic assessment across the entire female genital tract, offering a significant advancement in women’s healthcare worldwide. Full article