Search

Human papillomavirus (HPV) is an oncogenic DNA virus that plays a role in different cancer types. The aim of this study was to detect the prevalence and types of HPV and its relation with p16, EGFR and clinical findings in lung cancer. HPV and EGFR detection and genotyping of HPV were performed by polymerase chain reaction (PCR) and p16 by immunohistochemistry. Fifty lung cancer patients and seven patients with non-neoplastic lung disease were enrolled in this study. HPV was positive in 78% (39/50) of lung cancer cases. HPV 51 was the most frequent type, followed by HPV 16. Moreover, p16 was positive in 24% (12/50) of the cancer patients, and all of these patients were HPV-positive, while 27 HPV-positive patients showed no p16 expression. There was no relationship between HPV infection and p16 (p = 0.05), gender (p = 0.42), age (p = 0.38), or smoking history (p = 0.68). Although not statistically significant, the HPV prevalence was found to be higher in cancer patients compared to non-neoplastic patients. The prevalence of HPV in lung cancer varies across different studies, which may be due to differences in the detection methods, number of patients, geographic regions, and vaccination status. Further studies are necessary to understand the role of HPV in lung cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Most high-risk oral human papillomavirus research has focused on prevalent HPV16 and HPV18, with fewer studies focused on other high-risk strains incorporated into the nine-valent HPV vaccine. Therefore, the objective of this study was to determine the oral prevalence of non-HPV16 and non-HPV18 high-risk strains. A total of n = 251 existing biorepository saliva samples were screened using validated primers and qPCR. A total of n = 72 samples tested positive for HPV, including HPV31, HPV33, HPV35, HPV52, and HPV58. In addition, there were also significant increases in the prevalence of these high-risk strains (2011–2014, 21.3%) following the nine-valent HPV vaccine's introduction (2015–2019, 36.2%). However, the distribution of HPV-positive samples was nearly equal among males and females (52.8%, 47.2%, respectively, p = 0.5485), although the majority (66.7%) of the HPV-positive samples were within the HPV vaccination age (11 to 26 years) or catch-up range (27 to 45 years). These data demonstrated that the prevalence of high-risk oral HPV may be higher than anticipated, highly concentrated among patients within the recommended vaccination age range, and may be increasing over time—providing new evidence and support for the nine-valent HPV vaccine that covers these additional high-risk HPV strains. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant protein A (SP-A) as a novel molecule capable of recognising HPV16 pseudovirions (HPV16-PsVs) and reducing infection in a murine cervicovaginal HPV challenge model. Building on these findings, our current study aimed to assess SP-A's suitability as a broad-spectrum HPV-targeting molecule and its impact on innate immune responses. We demonstrate SP-A's ability to agglutinate and opsonise multiple oncogenic HPV-PsVs types, enhancing their uptake and clearance by RAW264.7 murine macrophages and THP-1 human-derived immune cells. The SP-A opsonisation of HPV not only led to increased lysosomal accumulation in macrophages and HaCaT keratinocytes but also resulted in a decreased infection of HaCaT cells, which was further decreased when co-cultured with innate immune cells. An analysis of human innate immune cell cytokine profiles revealed a significant inflammatory response upon SP-A exposure, potentially contributing to the overall inhibition of HPV infection. These results highlight the multi-layered impact of SP-A on HPV, innate immune cells and keratinocytes and lay the basis for the development of alternative prophylactic interventions against diverse HPV types. [ABSTRACT FROM AUTHOR]

Simple Summary: The study examined the relationship between Human Papillomavirus (HPV) and various types of skin cancer, including squamous cell carcinoma, basal cell carcinoma, and melanoma. It aimed to assess how HPV influenced the likelihood of developing these cancers, considering factors such as age, gender, urbanization, and existing health conditions. Through statistical models, the research quantified the risk of skin cancer in individuals with HPV compared to those without, underscoring how behaviors related to sun exposure and protection practices could alter these risks. The findings were crucial for guiding prevention and treatment strategies and were of significant interest to medical professionals and public health policymakers. Overall, the study enhanced our understanding of the risks associated with HPV, potentially leading to more effective health interventions. Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96–7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70–5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14–5.74), and melanoma (aHR = 4.36, 95% CI: 2.76–6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) causes 5% of cancers and is the main cause of oropharyngeal cancer in the United States and of cervical cancer worldwide. HPV proteins induce DNA damage and exploit and hijack the host DNA damage response. The HPV oncoproteins E6 and E7 induce chromosomal instability (CIN), or chromosome missegregation during mitosis, which also causes DNA damage and can lead to profound genetic alterations in the host cell. Though these features are known to contribute to HPV-induced carcinogenesis, how this affects tumor cell response to DNA damaging treatments is not well understood. Here, we review how HPV induces DNA damage and activates the DNA damage response and how the HPV-induced CIN likely exacerbates this. We then discuss how this viral protein-mediated DNA damage may affect the efficacy of chemoradiation therapy. High-risk human papillomaviruses (HPVs) are the main cause of cervical, oropharyngeal, and anogenital cancers, which are all treated with definitive chemoradiation therapy when locally advanced. HPV proteins are known to exploit the host DNA damage response to enable viral replication and the epithelial differentiation protocol. This has far-reaching consequences for the host genome, as the DNA damage response is critical for the maintenance of genomic stability. HPV+ cells therefore have increased DNA damage, leading to widespread genomic instability, a hallmark of cancer, which can contribute to tumorigenesis. Following transformation, high-risk HPV oncoproteins induce chromosomal instability, or chromosome missegregation during mitosis, which is associated with a further increase in DNA damage, particularly due to micronuclei and double-strand break formation. Thus, HPV induces significant DNA damage and activation of the DNA damage response in multiple contexts, which likely affects radiation sensitivity and efficacy. Here, we review how HPV activates the DNA damage response, how it induces chromosome missegregation and micronuclei formation, and discuss how these factors may affect radiation response. Understanding how HPV affects the DNA damage response in the context of radiation therapy may help determine potential mechanisms to improve therapeutic response. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a common sexually transmitted infection. Despite a safe and effective vaccine, uptake continues to be suboptimal. Recently, focus has moved to college campuses in an effort to increase vaccination rates. Little is known about the extent of efforts to reach graduate students on college campuses in the United States and the vaccination rates within this subpopulation. This scoping review assessed the literature on knowledge, attitudes, beliefs, and behaviors about HPV and HPV vaccination among graduate and post-baccalaureate professional students in the United States. This review also aims to identify areas for further research to improve institutions' abilities to create health programming to increase HPV awareness and HPV vaccination coverage on their campuses. Publications focusing on knowledge, attitudes, beliefs, and behaviors about HPV and HPV vaccination in post-baccalaureate students were included. The systematic review of PubMed, CINAHL, and Embase identified 2562 articles, and 56 articles met all inclusion criteria and were included in this scoping review. A majority of the reviewed studies investigated some combination of knowledge, attitudes, behaviors, and beliefs about HPV and the HPV vaccine in students in professional programs such as medicine. Study design approaches were primarily cross-sectional, utilizing web-based survey distribution methods. HPV vaccination status and HPV screening behaviors were primarily measured through participant self-report. There is limited research investigating post-baccalaureate student knowledge, attitudes, beliefs, and behaviors about HPV and HPV vaccination. There is a need for researchers to further investigate the needs of graduate students to create informative and effective HPV programming. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is associated with cellular changes in the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing the loop electrosurgical excision procedure (LEEP), a treatment for high-grade cervical intraepithelial neoplasia (CIN2+), remain at risk of recurrence. This study assessed the effect of post-conization HPV vaccination on the viral status of women at six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination statuses and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months of follow-up (ARR = 12.1%, p = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing the recurrence of high-grade cellular changes. However, the retrospective design and the insufficient control of confounding variables in this study underscore the need for further studies to confirm these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Persistent infection with high-risk HPV is the main cause of cervical cancer. However, the changes in epigenetics and viral load (VL) during persistent HPV infection are not well understood. This study selected individuals with a persistent HPV infection but without developing high-grade cervical lesions, analyzed the changes in PAX1/JAM3 methylation and VL according to the duration of HPV infection, and found that in women with HPV infections persisting for more than 3 years, there is a notable increase in the methylation levels of PAX1/JAM3, which could be used as cumulative evidence of persistent HPV infection before the occurrence of precancerous lesions. HPV infection persisting for more than 3 years is more likely to be associated with vaginal lesions, and HPV VL could be used as an indicative biomarker for concurrent cervical–vaginal lesions, which might be helpful to provide a clinical perspective for monitoring and intervention of individuals with persistent HPV infection. The relationship of PAX1/JAM3 methylation as well as HPV viral load (VL) with cervical lesions has been reported, but their role in persistent HPV infection without cervical high-grade lesions has not been fully elucidated. A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People's Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively. The average age of individuals with HPV infection lasting more than 3 years was higher compared to those with less than 3 years (48.9 vs. 45.1 years), with a statistically significant difference. Among the participants, 81.8% (189/231) had no previous screening. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). There was a significant correlation between PAX1 and JAM3 methylation (p < 0.001), which could be used as cumulative evidence of HPV infection duration before the occurrence of precancerous lesions. The incidence of vaginal intraepithelial lesions was higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, and HPV VL can be used as an indicative biomarker for concurrent cervical–vaginal lesions, especially for HPV other than 16/18 genotypes. [ABSTRACT FROM AUTHOR]

The Human Papillomavirus (HPV) is a frequently occurring sexually transmitted infection in adults and is associated with various cancers that can affect both males and females. Recently, the Advisory Committee on Immunization Practices (ACIP) expanded its recommendations for the HPV vaccine to include patients aged 27–45 years with shared clinical decision-making. A commonly reported obstacle to receiving the HPV vaccine among adults is a lack of healthcare provider recommendations. Considering the suboptimal HPV vaccine coverage figures and noting that the vast majority of hesitancy research has been conducted among children and adolescents, limited research is available on the adult perception of HPV vaccination in pharmacies. This study focuses on understanding adults' opinions and perceptions regarding the role of pharmacists in the uptake of the HPV vaccine and awareness of its availability in the pharmacy setting. Methods: After receiving approval from the Institutional Review Board (IRB), the qualitative study was initiated using virtual focus groups (FGs). Concepts from the Transtheoretical Model, the Health Belief Model, and the Social Cognitive Theory guided the study design. The corpus of data was collected in 2021 and 2022 by two researchers, and a third party transcribed the FGs to avoid any biases. The data were analyzed using Braun and Clarke's Thematic Analysis. Results: Out of 35 subjects that participated in six FGDs, most identified as female, with ages ranging from 18 to 45 years. The following four themes emerged: (1) HPV vaccine awareness; (2) stigmas leading to reduced education and vaccination rates; (3) education preferences; (4) follow-up in vaccination series reminders and preferences. Conclusion: Participants' views of the HPV vaccine and the ability to receive the vaccine in a pharmacy are influenced by a myriad of factors. Common factors include improved awareness, preferences for educational modalities, avoiding stigmas associated with HPV vaccination, combating gender-focused biases, and preferences for the location of vaccination. These barriers provide opportunities for pharmacists to promote and enhance vaccine uptake. [ABSTRACT FROM AUTHOR]

Approximately 12% of human cancers worldwide are associated with infectious agents, which are classified by the International Agency for Research on Cancer (IARC) as Group 1 within the agents that are carcinogenic to humans. Most of these agents are viruses. Group 1 oncogenic viruses include hepatitis C virus, hepatitis B virus (HBV), human T-cell lymphotropic virus type 1, Epstein-Barr virus, Kaposi sarcoma-associated herpesvirus, human immunodeficiency virus-1 and high-risk human papillomaviruses (HPVs). In addition, some human polyomaviruses are suspected of inducing cancer prevalently in hosts with impaired immune responses. Merkel cell polyomavirus has been associated with Merkel cell carcinoma and included by the IARC in Group 2A (i.e., probably carcinogenic to humans). Linking viruses to human cancers has allowed for the development of diagnostic, prophylactic and therapeutic measures. Vaccination significantly reduced tumours induced by two oncogenic viruses as follows: HBV and HPV. Herein, we focus on mucosal alpha HPVs, which are responsible for the highest number of cancer cases due to tumour viruses and against which effective prevention strategies have been developed to reduce the global burden of HPV-related cancers. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) can be vertically transmitted. Our objective was to measure the association between the mode of delivery and the detection of HPV in infants. We used data collected from pregnant women during the HERITAGE study. Self-collected vaginal samples from the first and third trimester were obtained for HPV testing. Specimens from oral, pharyngeal, conjunctival and anogenital mucosa were collected from infants 36–48 h after delivery and at 3 months of age. All samples were tested for HPV DNA by the Linear Array assay. Adjusted odd ratios (aOR) and 95% confidence interval (CI) were estimated using multivariate logistic regressions. From the 282 women revealed to be HPV-positive in both the first and third trimesters, 25 infants were born HPV-positive. The overall probability of transmission was 8.9% (25/282); 3.7% (3/81) in participants with a caesarean section and 10.9% (22/201) for those who delivered vaginally. Vaginal delivery increased the risk of HPV in infants compared to caesarean (aOR: 3.63, 95%CI: 1.03–12.82). Infants born after a caesarean with ruptured membranes were not at increased risk of HPV compared to infants born after an elective caesarean section with intact membranes (aOR: 1.31, 95%CI: 0.10–17.76). Our results support the hypothesis that transmission occurs mostly during the passage in the vaginal canal. [ABSTRACT FROM AUTHOR]

Recent evidence shows increased preterm birth risk with human papillomavirus-16 (HPV16) infection during pregnancy. This study aimed to measure the association between HPV16 viral load during pregnancy and preterm birth. We used data from participants in the HERITAGE study. The Linear Array assay was used for HPV DNA testing on vaginal samples collected during the first and third trimesters of pregnancy. The HPV16 viral load was measured with a real-time polymerase chain reaction. We used logistic regression to measure the associations between HPV16 viral load during pregnancy and preterm birth (defined as birth before 37 weeks of gestation). The adjusted odd ratios (aORs) and the 95% confidence intervals [CIs] were estimated with inverse probability treatment weighting of the propensity score. This study included 48 participants who tested positive for HPV16 during the first trimester of pregnancy. The aOR for the association between first-trimester HPV16 viral load (higher viral load categorized with a cutoff of 0.5 copy/cell) was 13.04 [95% CI: 1.58–107.57]). Similar associations were found using different cutoffs for the categorization of viral load during the first and third trimesters. Our findings suggest a strong association between a high HPV16 viral load during pregnancy and preterm birth, demonstrating a biological gradient that reinforces the biological plausibility of a causal association. [ABSTRACT FROM AUTHOR]

Background: Human Papillomavirus (HPV) vaccination rates are still below the target due to vaccine refusal or delay, lack of knowledge, and logistical challenges. Understanding these barriers is crucial for developing strategies to improve HPV vaccination rates. Methods: This cross-sectional study used a questionnaire to investigate social and behavioral factors influencing decision making about the HPV vaccine. The survey was conducted from 11 April to 29 May 2022 and involved 10,000 Italian citizens aged ≥ 18 years. The sample was stratified based on region of residence, gender, and age group. Results: 3160 participants were surveyed about themselves, while 1266 respondents were surveyed about their children's vaccine uptake. Among females aged ≥ 26 years, the national average HPV vaccine uptake was 21.7%, with variations across different regions. In the 18–25 age group, females had a vaccine uptake (80.8%) twice as much as males (38.1%), while vaccine uptake among male and female children aged 9–11 was similar. Conclusions: The OBVIOUS study in Italy reveals factors influencing low HPV vaccine uptake, suggesting targeted approaches, tailored information campaigns, heightened awareness of eligibility, promoting early vaccination, addressing low-risk perception among males, addressing safety concerns, and enhancing perceived accessibility to improve vaccine uptake and mitigate health risks. [ABSTRACT FROM AUTHOR]

Simple Summary: This study provides a thorough examination of various aspects of cervical cancer, using clinical and molecular datasets from four cohorts of patients across four continents. This integrative analysis explores the relationships between cervical cancer stages, productive human papillomavirus (HPV) integration, and the resulting malignant genetic mutations. The clinical data showed that cervical cancer and its stages were positively correlated with high-risk HPV infection and integration. At the molecular level, biological processes related to HPV infection, cancer-related conditions, and viral carcinogenesis were associated with the most significantly enriched pathways. The clinical and molecular findings further establish the prominent role of HPV infection and integration leading to genetic mutation underpinning cervical cancer and its stages across cohorts of different races and regions. Cervical cancer represents a significant global health concern, stemming from persistent infections with high-risk types of human papillomavirus (HPV). The understanding of cervical cancer's clinical correlates, risk factors, molecular mechanisms, stages, and associated genetic mutations is important for early detection and improved treatment strategies. Through integrated analysis of clinical and molecular datasets, this study aims to identify key factors that are overlapping and distinct across four cohorts of different races and regions. Here, datasets from four distinct cohorts of patients from Uganda (N = 212), the United States of America (USA) (N = 228), China (N = 106), and Venezuela (N = 858) were examined to comprehensively explore the relationships between cervical cancer stages, HPV types (clades), productive HPV integration, and malignant genetic mutations. Cohort-specific findings included the occurrence frequencies of cervical cancer stages and grades. The majority of patients from the USA and China were diagnosed with stages I and II, while those from Uganda were diagnosed with stages II and III, reflecting levels of awareness and the availability of HPV vaccines and screening services. Conversely, cervical cancer and its stages were positively correlated with HPV types (clades), HPV integration, and risk-factor habits across the cohorts. Our findings indicate that the more common squamous cervical cancer can be potentially due to productive HPV16 (clade 9) integration. At the molecular level, pathways related to HPV infection, cancer-related conditions, and viral carcinogenesis were among the most significant pathways associated with mutated genes in cervical cancer (across cohorts). These findings collectively corroborate the prominent role of HPV infection and integration leading to genetic mutation and hence to the development of cervical cancer and its stages across patients of distinct races and regions. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STIs). However, despite widespread under-vaccination amongst men and the importance of vaccinating both sexes to curb the spread of HPV, research has focused on promoting HPV vaccination predominantly amongst women. Therefore, the current study examines the effectiveness of different informational interventions in promoting vaccination intentions amongst heterosexual men. In a preregistered study of 583 unvaccinated adult men, we randomly assigned participants to one of four informational interventions aimed at promoting awareness of HPV risks and vaccine uptake: (1) risks to oneself (n = 145), (2) risks to their female partner (n = 144), (3) risks to oneself and their female partner (n = 153), and (4) general vaccine information (n = 153). Amongst participants reporting a sexual history (67%), intentions to get vaccinated significantly increased by 10.75 points on a 100-point scale (p < 0.01) after they received information about the risks of HPV for both themselves and their female partner, compared to receiving information about only their own HPV risk. These findings provide valuable guidance for public health officials and policymakers into the effectiveness of different messaging strategies in promoting HPV vaccination amongst adult male populations to increase vaccination rates. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) are a large family of viruses with a capsid composed of the L1 and L2 proteins, which bind to receptors of the basal epithelial cells and promote virus entry. The majority of sexually active people become exposed to HPV and the virus is the most common cause of cervical cancer. Vaccines are available based on the L1 protein, which self-assembles and forms virus-like particles (VLPs) when expressed in yeast and insect cells. Although very effective, these vaccines are HPV type-restricted and their costs limit broad vaccination campaigns. Recently, vaccine candidates based on the conserved L2 epitope from serotypes 16, 18, 31, 33, 35, 6, 51, and 59 were shown to elicit broadly neutralizing anti-HPV antibodies. In this study, we tested whether E. coli outer membrane vesicles (OMVs) could be successfully decorated with L2 polytopes and whether the engineered OMVs could induce neutralizing antibodies. OMVs represent an attractive vaccine platform owing to their intrinsic adjuvanticity and their low production costs. We show that strings of L2 epitopes could be efficiently expressed on the surface of the OMVs and a polypeptide composed of the L2 epitopes from serotypes 18, 33, 35, and 59 provided a broad cross-protective activity against a large panel of HPV serotypes as determined using pseudovirus neutralization assay. Considering the simplicity of the OMV production process, our work provides a highly effective and inexpensive solution to produce universal anti-HPV vaccines. [ABSTRACT FROM AUTHOR]

The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of precancerous lesions. We conducted a cross-sectional analysis involving 469 women who attended the Colposcopy Unit at the European Institute of Oncology in Milan, Italy, from December 2006 to December 2014. HPV type richness was measured as the number of different genotypes per patient. We calculated the associations between richness and age, as well as histologic grade, along with Simpson's biodiversity index for cervical dysplasias. We observed significant inverse relationships between the richness of high-risk (HR) genotypes and both age (p = 0.007) and histologic grade (p < 0.001). Furthermore, as the histologic grade increased, the mean biodiversity index of cervical dysplasias decreased, with exceptions noted in cases of normal histology and adenocarcinoma in situ. Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. These findings suggest that HPV genotype richness and the biodiversity of cervical dysplasias may play a crucial role in predicting the risk of high-grade cervical lesions, enabling personalized management of precancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Many previous studies have focused on the prevalence of high-risk HPV16 and HPV18 strains, highly associated with cervical and oral cancers covered by the original HPV vaccine. However, little research is currently available regarding the oral prevalence of other high-risk HPV strains, such as HPV31 and HPV33, which are part of the recently revised nine-strain HPV vaccine. This study conducted one of the first oral prevalence studies of these high-risk HPV strains among a multi-ethnic patient population at a public dental school in Nevada. The results of this investigation revealed a significant percentage of children and adults in this study harbored one or more of these high-risk strains, which were mostly found among patients within the recommended vaccination or catch-up age range (9–45 years). Many human papillomavirus (HPV) strains induce cancer in the cervix and the oral cavity. Although high-risk strains including HPV16 and HPV18 are commonly known, additional high-risk strains including HPV31, HPV33, and HPV35 may also induce carcinogenesis, and much less is known about their prevalence. Using an approved protocol, samples from a salivary biorepository were screened to find pediatric and adult samples from a multi-ethnic, university-based patient clinic population. A total of N = 86 samples from the saliva biorepository met the quality and concentration standards and were screened for high-risk HPV. qPCR screening of adult samples revealed n = 10/45 or 22% were HPV31- or HPV33-positive. In addition, a total of n = 9/41 or 21.9% of pediatric samples were either HPV31- or HPV33-positive (or both). No samples harbored HPV35. Most samples were derived from patients within the recommended vaccination or catch-up age range (age 9–45 years). These results demonstrated that a significant percentage of patients harbor additional high-risk HPV strains within the oral cavity, including HPV31 and HPV33. These data support oral healthcare provider recommendations for the newer nine-valent vaccine, which includes both HPV31 and HPV33. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) vaccine prevents cancer and is highly effective; however, the uptake has been low in the United States of America (USA) and among the most vulnerable populations. A recent Center for Disease Control (CDC) report highlighted that approximately 13,000 new cases of cervical cancer are diagnosed each year in the USA. Although cervical cancer is considered treatable, especially when detected early, in the USA, approximately 4000 women die every year of cervical cancer. However, little is known about access and awareness among women in the USA. The objective of this article is to focus on the role played by clinical pharmacists in bringing awareness about the HPV vaccine. It offers recommendations to enhance the administration of the HPV vaccine. This rapid literature review revealed two significant themes: Disparities in healthcare access to the HPV vaccine among women and clinical roles in empowering women to access the HPV vaccine. This rapid review emphasizes the need for future research in enhancing awareness about HPV as a viable strategy for women. As an integral part of the healthcare team, pharmacists can significantly improve awareness and administer the HPV vaccine, yielding enhanced outcomes and cancer prevention. [ABSTRACT FROM AUTHOR]

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history, but the role of selection on and the drift of non-coding DNA motifs on HPV diversification is poorly understood. In this study, more than a thousand complete genomes representing Alphapapillomavirus types, lineages, and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions, and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the four nucleotides (A, C, G, T), codon usage, trimer usage, and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for the CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages. [ABSTRACT FROM AUTHOR]

Simple Summary: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). Especially one influential case-control study by D'Souza et al. was responsible for the definitive acceptance of "high risk sexual behavior" as being causatively involved in the etiology of HPV-driven OPSCC. Utilizing case-control studies can be problematic in respect to achieving reliable statistical inference. For generalizability and drawing conclusions for the general population, the selection of cases and controls studied is critical. Substantial bias can be introduced. Therefore, the aim of our study was to replicate these former findings in a nested case-control study of OPSCC patients and propensity score (PS)-matched unaffected controls from a large population-based German cohort study. Here we demonstrate discrepant findings regarding HR-SB being a risk factor for OPSCC. (1) Background: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). A highly influential case-control study by D'Souza et al. comparing OPSCC patients and ENT patients with benign diseases (hospital controls) established HR-SB as a putative etiological risk factor for OPSCC. Aiming to replicate their findings in a nested case-control study of OPSCC patients and propensity score (PS)-matched unaffected controls from a large population-based German cohort study, we here demonstrate discrepant findings regarding HR-SB in OPSCC. (2) Methods: According to the main risk factors for HNSCC (age, sex, tobacco smoking, and alcohol consumption) PS-matched healthy controls invited from the population-based cohort study LIFE and HNSCC (including OPSCC) patients underwent interviews, using AUDIT and Fagerström, as well as questionnaires asking for SB categories as published. Afterwards, by newly calculating PSs for the same four risk factors, we matched each OPSCC patient with two healthy controls and compared responses utilizing chi-squared tests and logistic regression. (3) Results: The HNSCC patients and controls showed significant differences in sex distribution, chronologic age, tobacco-smoking history (pack years), and alcohol dependence (based on AUDIT score). However, PS-matching decreased the differences between OPSCC patients and controls substantially. Despite confirming that OPSCC patients were more likely to self-report their first sexual intercourse before age 18, we found no association between OPSCC and HR-SB, neither for practicing oral-sex, having an increased number of oral- or vaginal-sex partners, nor for having casual sex or having any sexually transmitted disease. (4) Conclusions: Our data, by showing a low prevalence of HR-SB in OPSCC patients, confirm findings from other European studies that differ substantially from North American case-control studies. HR-SB alone may not add excess risk for developing OPSCC. [ABSTRACT FROM AUTHOR]

People living with HIV (PLH) experience higher rates of HPV infection as well as an increased risk of HPV-related disease, including malignancies. Although they are considered a high-priority group for HPV vaccination, there are limited data regarding the long-term immunogenicity and efficacy of HPV vaccines in this population. Seroconversion rates and geometric mean titers elicited by vaccination are lower in PLH compared to immunocompetent participants, especially in individuals with CD4 counts below 200 cells/mm3 and a detectable viral load. The significance of these differences is still unclear, as a correlate of protection has not been identified. Few studies have focused on demonstrating vaccine efficacy in PLH, with variable results depending on the age at vaccination and baseline seropositivity. Although waning humoral immunity for HPV seems to be more rapid in this population, there is evidence that suggests that seropositivity lasts at least 2–4 years following vaccination. Further research is needed to determine the differences between vaccine formulations and the impact of administrating additional doses on durability of immune protection. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is associated with precancerous lesions and cancer of the genital tract both in women and men. The high incidence of cervical cancer worldwide focused the research on this infection mainly in women and to a lesser extent in men. In this review, we summarized epidemiological, immunological, and diagnostic data associated with HPV and cancer in men. We presented an overview of the main characteristics of HPV and infection in men that are associated with different types of cancer but also associated with male infertility. Men are considered important vectors of HPV transmission to women; therefore, identifying the sexual and social behavioral risk factors associated with HPV infection in men is critical to understand the etiology of the disease. It is also essential to describe how the immune response develops in men during HPV infection or when vaccinated, since this knowledge could help to control the viral transmission to women, decreasing the incidence of cervical cancer, but also could reduce other HPV-associated cancers among men who have sex with men (MSM). Finally, we summarized the methods used over time to detect and genotype HPV genomes, as well as some diagnostic tests that use cellular and viral biomarkers that were identified in HPV-related cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite salvage surgery being a key treatment option for recurrent oropharyngeal squamous cell carcinoma, it is unclear how human papillomavirus (HPV) status affects survival rates. The aim of this study was to evaluate how salvage surgery impacts patient survival in the setting of HPV oropharyngeal cancer that recurred within the head and neck region. This scoping review of 32 studies found that only 18.8% of these articles evaluated survival data specific to salvage surgery patients, and 4 studies inconsistently reported survival endpoints, such as overall survival. These findings suggest that future studies can improve upon survival reporting to guide clinical management decisions for HPV-positive recurrent oropharyngeal cancer. Although HPV status is known to provide an improved prognosis in initial treatments of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), it is unclear how it affects patients who receive salvage surgery (SS), which has historically poor survival rates. The purpose of this study was to evaluate the role of SS for patients with locoregional recurrence (LRR) of HPV-positive OPSCC and its impact survival rates. We conducted a scoping review of literature through October 2022 and included 995 individuals. Survival endpoints, such as overall survival (OS), Kaplan–Meier curves, and median post-recurrence survival, were analyzed in addition to demographics. Of all studies, 18.8% (6/32) reported any survival data for SS patients, with the most prevalent reporting 2- and 5-year OS in two studies. Median post-recurrence survival was not reported for SS. These findings reveal the limited and unpredictable reporting of survival-specific data on SS for HPV-positive OPSCC. With limited survival assessment, it is difficult to assess the potential advantages and disadvantages of this therapy to guide clinical decision-making. [ABSTRACT FROM AUTHOR]

The activin–follistatin system regulates several cellular processes, including differentiation and tumorigenesis. We hypothesized that the immunostaining of βA-activin and follistatin varies in neoplastic cervical lesions. Cervical paraffin-embedded tissues from 162 patients sorted in control (n = 15), cervical intraepithelial neoplasia (CIN) grade 1 (n = 38), CIN2 (n = 37), CIN3 (n = 39), and squamous cell carcinoma (SCC; n = 33) groups were examined for βA-activin and follistatin immunostaining. Human papillomavirus (HPV) detection and genotyping were performed by PCR and immunohistochemistry. Sixteen samples were inconclusive for HPV detection. In total, 93% of the specimens exhibited HPV positivity, which increased with patient age. The most detected high-risk (HR)-HPV type was HPV16 (41.2%) followed by HPV18 (16%). The immunostaining of cytoplasmatic βA-activin and follistatin was higher than nuclear immunostaining in all cervical epithelium layers of the CIN1, CIN2, CIN3, and SCC groups. A significant decrease (p < 0.05) in the cytoplasmic and nuclear immunostaining of βA-activin was detected in all cervical epithelial layers from the control to the CIN1, CIN2, CIN3, and SCC groups. Only nuclear follistatin immunostaining exhibited a significant reduction (p < 0.05) in specific epithelial layers of cervical tissues from CIN1, CIN2, CIN3, and SCC compared to the control. Decreased immunostaining of cervical βA-activin and follistatin at specific stages of CIN progression suggests that the activin–follistatin system participates in the loss of the differentiation control of pre-neoplastic and neoplastic cervical specimens predominantly positive for HPV. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) association is the most important predictor of survival in squamous cell carcinomas in the head and neck region (HNSCC). The role of HPV in cancer of unknown origin at this anatomic site (CUPHNSCC) is less well understood. The objective of this study was to identify prognostic classification markers in CUPHNSCC. Therefore, we investigated a consecutive cohort by multivariate modeling and testing for HPV DNA, mRNA, and p16INK4a (p16) expression. In 31% of CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%) of them, which was mostly consistent with mRNA detection. In contrast to oropharyngeal cancer, detection of p16 without additional detailed HPV testing appears to be more appropriate for the classification of CUPHNSCC. Three risk groups can be stratified based on performance status and p16, but additional factors may become important in future data or for cases with particular risk profiles. Background: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. Methods: We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000–2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. Results: In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. Conclusions: Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles. [ABSTRACT FROM AUTHOR]

To determine the value of low-risk human papillomavirus (HPV) PCR to screen for "high-grade anal squamous intraepithelial lesion and anal cancer" (HSIL-plus), rate of patients with low-grade anal squamous intraepithelial lesion (LSIL) progressing to HSIL-plus, and progression-related factors. Prospective, longitudinal study of consecutive MSM-LHIV attended between May 2010 and December 2021 and followed for 43 months (IQR: 12–76). HIV-related variables were gathered at baseline, performing anal cytology for HPV detection/genotyping, thin-layer cytological study, and high-resolution anoscopy (HRA). Follow-up was annual when HRA was normal or LSIL, and post-treatment in cases of HSIL-plus, re-evaluating sexual behavior, viral-immunological status, and HPV infection of anal mucosa. The 493 participants had mean age of 36 years: CD4 nadir < 200 cells/uL in 23.1%, virological failure in 4.1%, and tetravalent HPV vaccine > 5 years earlier in 15%. HSIL-plus was ruled out in patients with monoinfection by low-risk HPV genotype and normal cytology (100% sensitivity, 91.9% specificity, PPV 2.9%, and NPV 100%). Progression from LISL to HSIL-plus occurred in 4.27% of patients within 12 months (IQR: 12–12): risk factors were acquisition of high-risk (HR: 4.15; 95% CI: 1.14–15.03) and low-risk (HR: 3.68 95% CI: 1.04–12.94) HPV genotypes, specifically genotype 6 (HR: 4.47, 95% CI: 1.34–14.91), and history of AIDS (HR: 5.81 95% CI: 1.78–18.92). Monoinfection by LR-HPV genotypes in patients with normal cytology is not associated with anal cancer or precursor lesions. Progression from LSIL to HSIL-plus, observed in <5% of patients, was related to acquisition of HR and LR HPV genotypes, especially 6, and a history of AIDS. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) are responsible for one of the most common sexually transmitted diseases in the world, and their oncogenic role has been well demonstrated in genital, anal, and oropharyngeal areas. However, a certain distrust and a lack of knowledge about this vaccine are perceptible among French adolescents and their parents. Thus, health professionals and, more particularly, pharmacists appear to be key persons to promote HPV vaccination and restore confidence in the target population. The present study aims to assess the knowledge, attitudes, and practices regarding HPV vaccination among pharmacists, particularly in boys, following the 2019 recommendation to vaccinate them. The present study was designed as a cross-sectional, quantitative, and descriptive survey that was conducted from March to September 2021 among pharmacists in France. 215 complete questionnaires were collected. Gaps in knowledge were found, only 21.4% and 8.4% obtained a high level of knowledge related to, respectively, HPV and vaccination. Pharmacists were confident in the HPV vaccine (94.4%), found it safe and useful, and felt that the promotion of the vaccine was part of their role (94.0%). However, only a few have already advised it, which they justify due to a lack of opportunity and forgetfulness. Faced with this, training, computerized reminders, or supportive materials could be implemented to improve the advice and thus the vaccination coverage. Finally, 64.2% were in favor of a pharmacy-based vaccination program. In conclusion, pharmacists are interested in this vaccination and the role of promoter. However, they need the means to facilitate this mission: training, computer alerts, supportive materials such as flyers, and the implementation of vaccination in pharmacies. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection detected in oropharyngeal squamous cell carcinoma (OPSCC) is associated with a better survival outcome from previous literature. However, Thailand and several Asian countries have a low prevalence of HPV-associated OPSCC and, therefore, have a low positive rate of immunostaining with p16. Tumor microenvironments (TME), including tumor-infiltrating CD8+ lymphocytes (CD8+ TIL) and programmed death ligand 1 (PD-L1), are proposed as significant prognostic indicators in addition to p16. Objectives: Explore the expression p16, CD8+ TIL, and PD-L1 and its value as prognostic indicators for overall survival (OS) in patients with OPSCC. Materials and Methods: Data from patients with OPSCC diagnosed from 2012 to 2018 were recovered from medical records and national registry. All available glass slides and slides of immunohistochemistry (IHC) of p16, CD8, and PD-L1 were reviewed. The TME was classified into four types according to the expression pattern of PD-L1 and CD8+TIL. Overall survival (OS) was assessed using the Kaplan–Meier method and Cox regression model analysis. Results: In 160 OPSCC patients, p16 was positive in 27 (16.88%). The density of CD8+ TIL was higher in the p16+ and PD-L1+ groups (p = 0.005, 0.039); however, there was no association between p16 and the status of PD-L1. P16 and CD8+ TIL were significant prognostic factors for better OS (p = 0.007, 0.001), but not PD-L1 status (p = 0.317). Among the four types of TME, carcinoma showed mainly type IV TME (PD-L1−/TIL+), while OPSCCs with type I TME (PD-L1+/TIL+) had the best survival outcome. Conclusions: The positivity of p16 and the density of CD8+ TIL were associated with better OS in OPSCC, while the status of PD-L1 was not significantly related to OS. OPSCC with type I TME (PD-L1+/TIL+) showed the best prognosis of all types of TME. [ABSTRACT FROM AUTHOR]

Eastern Europe continues to have the highest rates of cancer of the uterine cervix (CUC) and human papillomavirus (HPV) infection in Europe. Aim: The aim of this study was to investigate CUC trends in Bulgaria in the context of a lack of a population-based screening program and a demographic crisis. Methodology: This was a retrospective study of 7861 CUC patients who were registered in the Bulgarian National Cancer Registry (BNCR) between 2013 and 2020 and followed up with until March 2022. We used descriptive statistics and modeling to assess temporal trends in new CUC incidence rates and identify factors associated with survival. Results: Bulgaria's population has decreased by 11.5% between 2011 and 2021. The CUC incidence rate decreased from 29.5/100,000 in 2013 to 23.2/100,000 in 2020 but remains very high. The proportion of patients diagnosed in earlier stages of CUC has decreased over time. Up to 19% of patients with CUC in Bulgaria are diagnosed between the age of 35 and 44 years. The median survival was 101.5 months, with some improvement in later years (adjusted HR = 0.83 for 2017–2020). Conclusions: In countries with well-established population-based screening, CUC is nowadays considered a rare disease. However, it is not considered rare in Bulgaria. Population-based screening starting at an earlier age is the fastest way to improve outcomes. [ABSTRACT FROM AUTHOR]

Cervical cancer is a major cause of cancer death in women worldwide. Targeting human papillomavirus (HPV) viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing of HPV infected cervical cancer is of great potential benefit for cervical cancer treatment. Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for Toll-like receptor 4 (TLR4), and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8+ T cells response in mice. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as antitumor T cell response. We found that EDA-E7 could be efficiently captured by human PBMC derived dendritic cells (DCs) in vitro and induce DCs maturation. Importantly, this effect could work in synergy with the TLR ligand anti-CD40 agonist, polyinosinic-polycytidylic acid [poly (I:C)], R848, and CpG2216. EDA-E7 matured DCs could activate T cells and trigger an anti-tumor response in vitro. Single cell RNA sequencing and T cell targeted killing assay confirmed the activation of T cells by EDA-E7 matured DCs. Therefore, therapeutic vaccination with EDA-E7 fusion protein maybe effective for human cervical carcinoma treatment. [ABSTRACT FROM AUTHOR]

Immunogenic proteins in cancer are relevant targets for drug delivery. In Photodynamic Therapy (PDT), surface antigens have previously been used to deliver the photosensitizer (PS) to the tumor microenvironment for specific targeting. However, can we target intracellular antigens to achieve more than surface recognition? Can we possibly increase PS intracellular localization and prevent drug efflux at the same time? In this study, these questions were addressed by using a compound that can not only specifically recognize and bind to intracellular E6 oncoproteins in Human Papillomavirus (HPV)-Transformed cancer cells, but is also capable of enhancing transmembrane uptake using the cells' own active transport mechanisms. HPV-transformed SiHa cells were cultured in vitro, and the resistant subpopulation was isolated using Magnetic Activated Cell Sorting (MACS). PDT was performed on four different cell types with varying physiognomies in terms of HPV oncoprotein expression and physiological form. Results demonstrated that tagging PSs on a carrier molecule that specifically delivers the PS inside the cells that express the target proteins enhanced both cellular uptake and retention of the PS even in the presence of drug efflux proteins on resistant subpopulations. These findings provide insight into the possibility of preventing cell-mediated resistance to PDT. [ABSTRACT FROM AUTHOR]

Simple Summary: Current treatments for cervical cancer patients include surgery, radiation and chemotherapy, which may be combined. Unfortunately, it is not always possible to remove all of the cancer and some cancer cells may be resistant to radio-/chemotherapy. This can result in lack of disease control or cancer relapse after initial response to therapy. Furthermore, metastasis of the tumor cells presents another difficult therapeutic challenge. The advent of novel immunotherapies, including monoclonal antibodies and genetically modified immune cells, that augment anti-cancer activity of immune cells holds great promise to improve cervical cancer patient survival. Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases, immunotherapies may be useful based on promising preclinical work, some of which has been successfully translated to the clinic. For example, approaches using monoclonal antibodies directed against surface proteins important for control of immune checkpoints (i.e., immune checkpoint inhibitors) were shown to improve outcome in many cancer settings, including cervical cancer. Additionally, initial clinical studies showed that application of cytotoxic immune cells modified to express chimeric antigen receptors (CAR) or T cell receptors (TCR) for better recognition and elimination of tumor cells may be useful to control cervical cancer. This review explores these important topics, including strengths and limitations of standard and developing approaches, and how some novel treatment strategies may be optimally used to offer the best possible treatment for cervical cancer patients. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) are high-risk causative factors for HPV infection. This infection does not come alone; it is often seen with co-infection with other viruses and acts as a causative agent for several malignancies. The major purpose of this comprehensive study was to highlight some recent advances in biotechnology associated with HPV infection, including understanding its host interactions and cancerous progression. A systematic research strategy was used to gather data from recent, and the most advanced published electronic sources. The compiled data explain the recent understanding of biology, host–viral interaction cycles, co-infection with other viral diseases, and cellular transformation toward malignancies associated with HPV. In recent years, some vaccination protocols have been introduced in the form of live attenuated, subunit, and DNA-based vaccines. Moreover, some strategies of nanotechnology are being employed to synthesize drugs and vaccines with a whole new approach of plant-based products. The data are immense for the proposed research question, yet the need is to implement modern follow-up screening and modern therapeutics at the clinical level and to conduct wide-scale public awareness to lessen the HPV-related disease burden. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the second most common cancer in women worldwide and the fourth leading cause of cancer-associated death in women. Although human papillomavirus (HPV) infection is associated with nearly all CC, it has recently become clear that HPV−negative (HPV−) CC represents a distinct disease phenotype with increased mortality. HPV−positive (HPV+) and HPV− CC demonstrate different molecular pathology, prognosis, and response to treatment. Furthermore, CC caused by HPV α9 types (HPV16-like) often have better outcomes than those caused by HPV α7 types (HPV18-like). This study systematically and comprehensively compared the expression of genes involved in major histocompatibility complex (MHC) class I and II presentation within CC caused by HPV α9 types, HPV α7 types, and HPV− CC. We observed increased expression of MHC class I and II classical and non-classical genes in HPV+ CC and overall higher expression of genes involved in their antigen loading and presentation apparatus as well as transcriptional regulation. Increased expression of MHC I-related genes differs from previous studies using cell culture models. These findings identify crucial differences between antigen presentation within the tumor immune microenvironments of HPV+ and HPV− CC, as well as modest differences between HPV α9 and α7 CC. These differences may contribute to the altered patient outcomes and responses to immunotherapy observed between these distinct cancers. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the impact of adverse lifestyle factors on outcomes in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Methods: From 2010 to 2019, 150 consecutive non-metastatic OPSCC patients receiving curative treatment in our institution were retrospectively enrolled. HPV positivity was defined as p16 expression ≥75%. The effects of adverse lifestyle factors on overall survival (OS) and disease-free survival (DFS) on OPSCC patients were determined. Results: The median follow-up duration was 3.6 years. Of the 150 OPSCCs, 51 (34%) patients were HPV-positive and 99 (66%) were HPV-negative. The adverse lifestyle exposure rates were 74.7% (n = 112) alcohol use, 57.3% (n = 86) betel grid chewing, and 78% (n = 117) cigarette smoking. Alcohol use strongly interacted with HPV positivity (HR, 6.00; 95% CI, 1.03–35.01), leading to an average 26.1% increased risk of disease relapse in patients with HPV-positive OPSCC. Heavy smoking age ≥30 pack-years was associated with increased risk of death (HR, 2.05; 95% CI, 1.05–4.00) and disease relapse (HR, 1.99; 95% CI, 1.06–3.75) in OPSCC patients. In stratified analyses, the 3-year absolute risk of disease relapse in HPV-positive OPSCC patients reached up to 50% when alcohol use and heavy smoking for ≥30 pack-years were combined. Conclusions: Alcohol acted as a significant treatment-effect modifier for DFS in HPV-positive OPSCC patients, diluting the favorable prognostic effect of HPV positivity. Heavy smoking age ≥30 pack-years was an independent adverse prognostic factor of OS and DFS in OPSCC patients. De-intensification treatment for HPV-related OPSCC may be avoided when these adverse lifestyle factors are present. [ABSTRACT FROM AUTHOR]

Simple Summary: Viruses are well known causes of several human malignancies. Oral squamous cell carcinoma (OSCC) is rising in patients with limited exposure to traditional risk factors, including smoking. As a causative factor of OSCC is yet to be found, our study aimed to identify a virus that may drive this cancer. First, we examined whole genome sequencing data from 28 patients under the age of 50 with limited exposure to carcinogens for viruses. Using viral detection software that screens for >700,000 viruses, we identified one 49 year old male patient with human papillomavirus (HPV). We further validated our findings in 657 patients, using immunohistochemistry and RNA in situ hybridization specific for HPV, and identified 8 (1.2%) male patients with HPV integration. Through a comprehensive search for viruses and evaluation in a large patient OSCC cohort, we demonstrate that viral integration occurs in a minority of male OSCC patients. Viruses are well known drivers of several human malignancies. A causative factor for oral cavity squamous cell carcinoma (OSCC) in patients with limited exposure to traditional risk factors, including tobacco use, is yet to be identified. Our study aimed to comprehensively evaluate the role of viral drivers in OSCC patients with low cumulative exposure to traditional risk factors. Patients under 50 years of age with OSCC, defined using strict anatomic criteria were selected for WGS. The WGS data was interrogated using viral detection tools (Kraken 2 and BLASTN), together examining >700,000 viruses. The findings were further verified using tissue microarrays of OSCC samples using both immunohistochemistry and RNA in situ hybridisation (ISH). 28 patients underwent WGS and comprehensive viral profiling. One 49-year-old male patient with OSCC of the hard palate demonstrated HPV35 integration. 657 cases of OSCC were then evaluated for the presence of HPV integration through immunohistochemistry for p16 and HPV RNA ISH. HPV integration was seen in 8 (1.2%) patients, all middle-aged men with predominant floor of mouth involvement. In summary, a wide-ranging interrogation of >700,000 viruses using OSCC WGS data showed HPV integration in a minority of male OSCC patients and did not carry any prognostic significance. [ABSTRACT FROM AUTHOR]

The FAM57A (family with sequence similarity 57 member A) gene is controversially discussed to possess pro- or anti-tumorigenic potential. Here, we analyze the regulation of cellular FAM57A protein levels and study the functional role of FAM57A in HPV-positive cervical cancer cells. We find that FAM57A protein expression strongly depends on cell density, with FAM57A being readily detectable at low cell density, but undetectable at high cell density. This regulation occurs post-transcriptionally and is not mirrored by corresponding changes at the RNA level. We further show that FAM57A protein levels are highly increased in cervical cancer cells cultivated at hypoxia compared to normoxia and provide evidence that FAM57A is a hypoxia-responsive gene under control of the α-subunit of the HIF-1 (hypoxia-inducible factor-1) transcription factor. Yet, the strong relative increase of FAM57A protein levels in hypoxic cells is predominantly cell-density-dependent and occurs post-transcriptionally. Other anti-proliferative effectors besides hypoxia, such as silencing of HPV E6/E7 oncogene expression in cervical cancer cells, also result in an increase of FAM57A levels compared to untreated cells. Functional analyses reveal that FAM57A repression leads to pronounced anti-proliferative as well as anti-migratory effects in cervical cancer cells. Taken together, these results provide insights into the regulation of FAM57A protein levels and reveal that they underlie a tight cell-density-dependent control. Moreover, they identify FAM57A as a critical determinant for the phenotype of cervical cancer cells, which promotes their proliferation and migration capacities. [ABSTRACT FROM AUTHOR]

Detection of p16 through immunohistochemistry (IHC) is the standard for determining the HPV status of the tumor according the TNM eighth edition released in 2017 and has become crucial for determining the HPV status of oropharyngeal squamous cell carcinomas (OPSCC) with direct impact on staging and prognostication. In recent years, detection of HPV DNA in mouthwashes has been proposed as a noninvasive alternative, both for OPSCCs and for other head and neck squamous cell carcinomas (HNSCCs). However, the prospect of using the mouthwashes to monitor the response to therapy is unclear. To evaluate the effect of curative therapy on the detection of HPV DNA, we performed a prospective study comparing the detection frequency of high-risk HPV DNA (HR-HPV-DNA) in pre- and post-therapy mouthwashes. We collected 137 mouthwashes from 88 pathologically confirmed HNSCC patients for DNA isolation and HPV genotyping with the Inno-LiPA assay. We show that HPV DNA in pretherapeutic mouthwashes can detect HPV-driven HNSCCs with a sensitivity of 50.0% and specificity of 85.4%, alongside a high negative predictive value of 79.5% and an accuracy of 74.5%. Furthermore, we observed a notable decrease in the detection frequency of HR-HPV-DNA after successful treatment (pre-therapy 50.0% (9/18) versus post-therapy 9.7% (3/28)). However, the comparatively low sensitivity regarding detection of HPV-driven OPSCC argues against its use in clinical routine. [ABSTRACT FROM AUTHOR]

Atherosclerosis manifests by the thickening of artery walls and their narrowed channels through the accumulation of plaque. It is one of the most important indicators of cardiovascular disease. It can be caused by various factors, such as smoking, a high cholesterol diet, hypertension, hyperglycemia, and genetic factors. However, atherosclerosis can also develop due to infection. It has been reported that some bacteria and viruses can cause the development of atherosclerosis. Examples of these viruses are influenza viruses, herpes viruses, hepatitis viruses, or papillomaviruses, which are all prevalent and eminent globally for infecting the population worldwide. Moreover, many patients with coronavirus disease 2019 (COVID-19) showed symptoms of cardiovascular disease. In this review paper, the viruses linked to the development of atherosclerosis are introduced, and their viral characteristics, the mechanisms of the development of atherosclerosis, and the current vaccines and antiviral treatment methods are summarized. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) causes cervical cancer among women and is associated with other anogenital cancers in men and women. Prophylactic particulate vaccines that are affordable, self-administered and efficacious could improve uptake of HPV vaccines world-wide. The goal of this research is to develop a microparticulate HPV16 vaccine for transdermal administration using AdminPatch® and assess its immunogenicity in a pre-clinical mouse model. HPV16 microparticles were prepared using a biocompatible polymer and characterized in terms of size, zeta potential, encapsulation efficiency and microparticle yield. Scanning and transmission electron microscopy were conducted to confirm particle image and to visualize the conformation of HPV16 vaccine particles released from microparticle formulation. In vivo studies performed to evaluate the potential of the microparticulate vaccine initiated a robust and sustained immune response. HPV16 IgG antibodies were significantly elevated in the microparticle group compared to antigen solutions administered by the transdermal route. Results show significant expansion of CD4+, CD45R, CD27 and CD62L cell populations in the vaccinated mice group, indicating the high efficacy of the microparticulate vaccine when administered via transdermal route. The findings of this study call attention to the use of minimally invasive, pain-free routes to deliver vaccine. [ABSTRACT FROM AUTHOR]

Simple Summary: HPV+ and HPV- HNSCC share distinct epigenetic characteristics and clinicopathological features. The aim of our study was to assess whether DNA methylation plays a role in the progression of HPV+ HNSCC. We used a HumanMethylation450 BeadChip array (Illumina) to identify PRKCZ genes exhibiting different levels of DNA methylation between HPV+ and HPV- HNSCC. PRKCZ acts as a potent tumor promoter in HPV+ HNSCC. These findings may provide a possible explanation for the differences in the clinicopathological characteristics between HPV+ and HPV- HNSCC and promising ideas for the treatment of HPV+ HNSCC. Purpose: To study the role of target genes with aberrant DNA methylation in HPV+ HNSCC. Methods: A HumanMethylation450 BeadChip array (Illumina) was used to identify differentially methylated genes. CCK-8, flow cytometry, wound healing, and cell invasion assays were conducted to analyze the biological roles of PRKCZ. Western blot, qRT-PCR, immunohistochemistry, and animal studies were performed to explore the mechanisms underlying the functions of PRKCZ. Results: We selected PRKCZ, which is associated with HPV infection, as our target gene. PRKCZ was hypermethylated in HPV+ HNSCC patients, and PRKCZ methylation status was negatively related to the pathological grading of HNSCC patients. Silencing PRKCZ inhibited the malignant capacity of HPV+ HNSCC cells. Mechanistically, HPV might promote DNMT1 expression via E6 to increase PRKCZ methylation. Cdc42 was required for the PRKCZ-mediated mechanism of action, contributing to the occurrence of epithelial-mesenchymal transition (EMT) in HPV+ HNSCC cells. In addition, blocking PRKCZ delayed tumor growth in HPV16-E6/E7 transgenic mice. Cdc42 expression was decreased, whereas E-cadherin levels increased. Conclusion: We suggest that PRKCZ hypermethylation induces EMT via Cdc42 to act as a potent tumor promoter in HPV+ HNSCC. [ABSTRACT FROM AUTHOR]

Vaccines constitute a pillar in the prevention of infectious diseases. The unprecedented emergence of novel immunization strategies due to the COVID-19 pandemic has again positioned vaccination as a pivotal measure to protect humankind and reduce the clinical impact and socioeconomic burden worldwide. Vaccination pursues the ultimate goal of eliciting a protective response in immunized individuals. To achieve this, immunogens must be efficiently delivered to prime the immune system and produce robust protection. Given their safety, immunogenicity, and flexibility to display varied and native epitopes, self-assembling protein nanoparticles represent one of the most promising immunogen delivery platforms. Currently marketed vaccines against the human papillomavirus, for instance, illustrate the potential of these nanoassemblies. This review is intended to provide novelties, since 2015, on the ground of vaccine design and self-assembling protein nanoparticles, as well as a comparison with the current emergence of mRNA-based vaccines. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the primary cause of female cancer fatalities in low-middle-income countries (LMICs). Persistent infections from the human papillomavirus (HPV) can result in cervical cancer. However, numerous different factors influence the development and progression of cervical cancer. Transcriptomic knowledge of the mechanisms with which HPV causes cervical cancer pathogenesis is growing. Nonetheless, there is an existing gap hindering the development of therapeutic approaches and the improvement of patient outcomes. Alternative splicing allows for the production of numerous RNA transcripts and protein isoforms from a single gene, increasing the transcriptome and protein diversity in eukaryotes. Cancer cells exhibit astounding transcriptome modifications by expressing cancer-specific splicing isoforms. High-risk HPV uses cellular alternative splicing events to produce viral and host splice variants and proteins that drive cancer progression or contribute to distinct cancer hallmarks. Understanding how viruses utilize alternative splicing to drive pathogenesis and tumorigenesis is essential. Although research into the role of miRNAs in tumorigenesis is advancing, the function of other non-coding RNAs, including lncRNA and circRNA, has been understudied. Through their interaction with mRNA, non-coding RNAs form a network of competing endogenous RNAs (ceRNAs), which regulate gene expression and promote cervical cancer development and advancement. The dysregulated expression of non-coding RNAs is an understudied and tangled process that promotes cervical cancer development. This review will present the role of aberrant alternative splicing and immunosuppression events in HPV-mediated cervical tumorigenesis, and ceRNA network regulation in cervical cancer pathogenesis will also be discussed. Furthermore, the therapeutic potential of splicing disruptor drugs in cervical cancer will be deliberated. [ABSTRACT FROM AUTHOR]

Simple Summary: Certain viruses, specifically, human papillomavirus (HPV) and Epstein–Barr virus (EBV), have been linked with the development of head and neck cancer. In this study, we review the mechanisms by which (these) viruses lead to cellular transformation and a chronic inflammatory state. Given that the head and neck host a rich microbiome (which itself is intrinsically linked to inflammation), we scrutinize the literature to highlight the interplay between viruses, cellular transformation, inflammation, and the local host microbiome in head and neck cancer. While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)—a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present (with about 1% of the population having high-risk oral HPV infection at any one time), less than 1% of those infected with high-risk strains develop OPSCC—suggesting that additional cofactors or coinfections may be required. Epstein–Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions—leading to tumor growth. [ABSTRACT FROM AUTHOR]

A growing number of individuals and organizations are turning to machine learning (ML) and deep learning (DL) to analyze massive amounts of data and produce actionable insights. Predicting the early stages of serious illnesses using ML-based schemes, including cancer, kidney failure, and heart attacks, is becoming increasingly common in medical practice. Cervical cancer is one of the most frequent diseases among women, and early diagnosis could be a possible solution for preventing this cancer. Thus, this study presents an astute way to predict cervical cancer with ML algorithms. Research dataset, data pre-processing, predictive model selection (PMS), and pseudo-code are the four phases of the proposed research technique. The PMS section reports experiments with a range of classic machine learning methods, including decision tree (DT), logistic regression (LR), support vector machine (SVM), K-nearest neighbors algorithm (KNN), adaptive boosting, gradient boosting, random forest, and XGBoost. In terms of cervical cancer prediction, the highest classification score of 100% is achieved with random forest (RF), decision tree (DT), adaptive boosting, and gradient boosting algorithms. In contrast, 99% accuracy has been found with SVM. The computational complexity of classic machine learning techniques is computed to assess the efficacy of the models. In addition, 132 Saudi Arabian volunteers were polled as part of this study to learn their thoughts about computer-assisted cervical cancer prediction, to focus attention on the human papillomavirus (HPV). [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is a leading cause of death for women in low-resource areas around the world. However, the disease can be prevented through vaccination, screening, and early treatment. Recently, the World Health Organization released a strategy with the goal of eliminating cervical cancer through a combination of these three preventive strategies. In El Salvador, a screening program has been in place for some years, and vaccination is in its early stages. Here, we describe the Salvadoran experience and discuss successes to date and challenges for the future. We also provide recommendations that may be helpful for other countries working to meet the WHO elimination goals. Cervical cancer is preventable through vaccination, early detection, and the treatment of pre-cancerous lesions. However, global inequalities mean that the disease remains a leading cause of cancer death around the world, with over 80% of new cases and 90% of deaths occurring in low- and middle-income countries (LMICs). In El Salvador, joint efforts between the Ministry of Health (MoH) and the non-profit organization Basic Health International (BHI) have been in place since 2008, with the goal of reducing the country's disease burden. While the World Health Organization's (WHO) call to action to eliminate cervical cancer provided worldwide momentum to implement new public health initiatives, the COVID-19 pandemic disrupted ongoing programs and jeopardized plans for the future. The purpose of this manuscript is to describe the progress that El Salvador has achieved in improving cervical cancer prevention, the impact of the pandemic on current strategies, and potential solutions that can help the country meet the WHO's strategic targets by 2030 to accelerate the elimination of cervical cancer. [ABSTRACT FROM AUTHOR]

Despite all precautionary actions and the possibility of using vaccinations to counteract infections caused by human papillomaviruses (HPVs), HPV-related cancers still account for approximately 5% of all carcinomas. Worldwide, many women are still excluded from adequate health care due to their social position and origin. Therefore, immense efforts in research and therapy are still required to counteract the challenges that this disease entails. The special thing about an HPV infection is that it is not only able to trick the immune system in a sophisticated way, but also, through genetic integration into the host genome, to use all the resources available to the host cells to complete the replication cycle of the virus without activating the alarm mechanisms of immune recognition and elimination. The mechanisms utilized by the virus are the metabolic, immune, and hormonal signaling pathways that it manipulates. Since the virus is dependent on replication enzymes of the host cells, it also intervenes in the cell cycle of the differentiating keratinocytes and shifts their terminal differentiation to the uppermost layers of the squamocolumnar transformation zone (TZ) of the cervix. The individual signaling pathways are closely related and equally important not only for the successful replication of the virus but also for the onset of cervical cancer. We will therefore analyze the effects of HPV infection on metabolic signaling, as well as changes in hormonal and immune signaling in the tumor and its microenvironment to understand how each level of signaling interacts to promote tumorigenesis of cervical cancer. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease. [ABSTRACT FROM AUTHOR]

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous group of tumors characterized by an incidence of 650,000 new cases and 350,000 deaths per year worldwide and a male to female ratio of 3:1. The main risk factors are alcohol and tobacco consumption and Human Papillomavirus (HPV) infections. HNSCC cases are divided into two subgroups, the HPV-negative (HPV−) and the HPV-positive (HPV+) which have different clinicopathological and molecular profiles. However, patients are still treated with the same therapeutic regimens. It is thus of utmost importance to characterize the molecular mechanisms underlying these differences to find new biomarkers and novel therapeutic targets towards personalized therapies. Epigenetic alterations are a hallmark of cancer and can be exploited as both promising biomarkers and potential new targets. E6 and E7 HPV oncoviral proteins besides targeting p53 and pRb, impair the expression and the activity of several epigenetic regulators. While alterations in DNA methylation patterns have been well described in HPV+ and HPV− HNSCC, accurate histone post-translational modifications (hPTMs) characterization is still missing. Herein, we aim to provide an updated overview on the impact of HPV on the hPTMs landscape in HNSCC. Moreover, we will also discuss the sex and gender bias in HNSCC and how the epigenetic machinery could be involved in this process, and the importance of taking into account sex and/or gender also in this field. [ABSTRACT FROM AUTHOR]