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To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines. [ABSTRACT FROM AUTHOR]

According to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV. EW1h6cVcK6kCY2-xSiZ8DW Video Abstract [ABSTRACT FROM AUTHOR]

Background: There is an increase in number of Human Papillomavirus related head and neck squamous cell carcinoma (HPV-related HNSCC) High risk HPV(HR-HPV) types can be cleared by an infected person, however, some can persist and develop HN cancer. There is a broad knowledge gap regarding HPV and related cancers. Main text: The aim of this review is to assess existing published knowledge on oral-genital HPV transmission, concordance of HPV genotypes and risk of oral or/and genital lesions among spouses/partners of patients diagnosed with HPV-related HNSCC, identify gaps in the current research and highlight areas that requires further inquiry. Method: Database like Pub med, Google Scholar, Scopus, Puplon, Wiley online library were used for search strategy. Published papers on transmission, concordance of HPV genotypes and genital lesions among spouses/partners of patients diagnosed with HPV-related HNSCC were included. Papers published from January1,2000 to October 31, 2022 were included. The published papers included are 8 Case reports, 2 cross-sectional studies, 3 Cohort studies and 2 systematic reviews. Results: A total of 2125 citations were retrieved from the five sources. 15papers were included. Case reports reported concurrent HPV-related oropharyngeal, tonsillar, unspecified HNSCC, laryngeal and nasopharyngeal carcinoma among couples. The two cross-sectional studies were done. Almost all the tumors taken from patients with HPV-related oropharyngeal carcinoma (HPV-related OPC) and their spouses were positive for identical HPV 16 type. The three cohort studies showed an increase risk of upper aero-digestive tract cancer among male spouses of females with cervical cancer. Two systematic reviews reviewed literature studies which evaluated concurrent cases of HPV-related Oropharyngeal cancers. Examination of these papers showed that the majority of the studies suggested that there is HPV transmission, concordance and risk of HNSCC cancer among spouses with HPV-related oral-genital cancer. No studies evaluated the risk of developing genital cancer in spouses of patients with HNSCC. Conclusion: The findings of this review highlighted big need of further research on oral-genital HPV infection among spouses of patients diagnosed with HPV-related HNSCC. Studies are needed to evaluate the risk of getting genital and upper aero-digestive tract HPV-related cancer among spouses with HPV-related HNC. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised persons have high risk of persistent human papillomavirus (HPV) infection and HPV-related diseases, and lower immune response to vaccines. This study evaluated the immunogenicity and safety of administering a fourth dose of quadrivalent (4v)HPV vaccine in immunosuppressed women who did not seroconvert after three doses. Methods: An open-label, not-controlled trial included immunosuppressed women (solid organ transplant patients and women receiving treatment for SLE) who did not seroconvert to at least one of the four HPV vaccine types after three 4vHPV vaccine doses. All participants received a fourth 4vHPV vaccine dose (median 27 months after third dose). Immunogenicity was evaluated a month after the fourth dose, by measuring seroconversion rates and antibody geometric mean concentration (GMC). Results: Twenty-three women were included. Among women who did not seroconvert for each vaccine type after three doses, 2/10 seroconverted to HPV6, 3/10 to HPV11, 3/10 to HPV16 and 6/18 to HPV18, after the fourth 4vHPV dose. There was an increase in antibody GMC for HPV 6, 16, 18, with highest increase for HPV16 (from 6.02 to 44.63 International Units). There was no increase of anti-HPV-11. Within seven days after vaccination, only three of the 23 vaccinees reported any adverse event, none of which were classified as serious. Conclusions: Although safe, the fourth 4vHPV vaccine dose led to seroconversion in only few immunosuppressed women who had not seroconverted after three doses. [ABSTRACT FROM AUTHOR]

Few studies have demonstrated the interplay between human immunodeficiency virus (HIV), anal human papillomavirus (HPV), and anal microbiota, especially in persons living with HIV who are men who have sex with men. We, therefore, explored these interrelationships in a cohort of persons living with HIV, mainly comprising men who have sex with men. HPV genotyping using a commercial genotyping kit and ThinPrep cytology interpreted by Bethesda systems was performed on samples from 291 patients. Samples were characterized by high-throughput sequencing of dual-index barcoded 16s rRNA (V3–4). Bacterial diversity was diminished in individuals living with HIV with CD4+ T cells <500 cells/μL and anal cytology yielding atypical squamous cells of undetermined significance or higher grades (ASCUS+) with detectable HPV 16/18 compared with those with CD4+ T cells ≥500 cells/μL with ASCUS+ and HPV 16/18 and those with normal anal cytology or inflammation without HPV 16/18. Enterobacteriaceae, Ruminococcus, and Bacilli were significantly abundant in persons living with HIV with CD4+ T cells <500 cells/μL with ASCUS+ and HPV 16/18. Bacterial diversity, composition, and homogeneity of dispersion were different in individuals living with HIV with low CD4+ T cells with ASCUS+ and HPV 16/18, and understanding the interaction among immunocompromised hosts, oncogenic HPVs, and microbiota is essential, and the contribution of these factors to anal precancerous lesions needs more in-depth exploration. [ABSTRACT FROM AUTHOR]

Simple Summary: This review elucidates the manner in which artificial intelligence (AI) is transforming the diagnosis and staging of squamous cell carcinomas of the oropharynx (OPSCC). The review examines the potential utilization of AI in discerning the status of human papillomavirus (HPV) in OPSCCs. AI is primarily employed in the analysis of imaging data and the interpretation of histological specimens. While the outcomes are encouraging, they require further validation before they can be adopted in clinical practice. Human papillomavirus (HPV) infection is sexually transmitted and commonly widespread in the head and neck region; however, its role in tumor development and prognosis has only been demonstrated for oropharyngeal squamous cell carcinoma (HPV-OPSCC). The aim of this review is to analyze the results of the most recent literature that has investigated the use of artificial intelligence (AI) as a method for discerning HPV-positive from HPV-negative OPSCC tumors. A review of the literature was performed using PubMed/MEDLINE, EMBASE, and Cochrane Library databases, according to PRISMA for scoping review criteria (from 2017 to July 2024). A total of 15 articles and 4063 patients have been included. Eleven studies analyzed the role of radiomics, and four analyzed the role of AI in determining HPV histological positivity. The results of this scoping review indicate that AI has the potential to play a role in predicting HPV positivity or negativity in OPSCC. Further studies are required to confirm these results. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis evaluate human papillomavirus (HPV) prevalence, genotype distribution, and associations with cervicovaginal microbiota and cytokine profiles among South African women, where cervical cancer ranks as the second most common cancer. PubMed, SCOPUS, and Web of Science were searched for studies on HPV infection up to 21 September 2024. The pooled prevalence was estimated using a random-effects model, with subgroup analyses by province, sample type, and HIV status. Publication bias was evaluated using funnel plots and Egger's test. Of the 19,765 studies screened, 120 met the inclusion criteria, comprising 83,266 participants. Results indicate a high HPV burden, with a pooled prevalence of 58% (95% CI: 52–64%), varying regionally from 53% (95% CI: 41–65%) to 64% (95% CI: 55–73%), with some regions under-researched. Cervical samples had the highest HPV prevalence (60% (95% CI: 54–66%)), while non-genital samples were less studied. High-risk (HR) HPV types, notably HPV 16 (7.5%), HPV 35 (4.1%), and HPV 18 (3.9%), were prominent, with HPV 35 emphasizing the need for expanded vaccine coverage. HIV-positive women had a higher pooled HPV prevalence (63% (95% CI: 55–71%)). Funnel plot analysis and Egger's test suggested a potential publication bias (p = 0.047). HPV-positive women exhibited lower Lactobacillus levels and an increase in Bacterial Vaginosis (BV)-associated species like Gardnerella, potentially supporting HPV persistence. Cytokine analysis showed elevated MIP-1α and MIP-1β in HPV infections, though cytokine profiles may depend on HPV genotypes. These findings underscore the need for research on HPV–microbiome-immune interactions and call for comprehensive HPV-prevention strategies, including vaccines targeting regional HPV types and tailored interventions for HIV-positive populations. [ABSTRACT FROM AUTHOR]

Vaccination against human papillomavirus (HPV) significantly reduces the incidence of HPV-related lesions worldwide. Considering the increasingly young age of patients in gynecological offices and earlier sexual initiation and potential contact with the HPV virus, doctors need the tools to verify diagnoses. Currently, women plan to pursue motherhood later, so it is necessary to consider whether sexual treatment in the form of, among others, loop electrosurgical excision procedures (LEEPs) may increase the risk of premature birth or difficulty dilating the cervix during labour. For this reason, to avoid the overtreatment of low-grade squamous intraepithelial lesions (LSILs), methylation testing may be considered. In patients with histopathologically confirmed high-grade squamous intraepithelial lesions (HSILs) during biopsy and, ultimately, a lower diagnosis, i.e., LSIL or no signs of atypia, methylation was found to be a useful tool. We performed a Pap smear, HPV genotyping, a punch biopsy, LEEP-conization (if needed), and methylation tests on 108 women admitted to the District Public Hospital in Poland. Women with a negative methylation test result were significantly more likely to be ultimately diagnosed with LSIL (p = 0.013). This means that in 85.7% of the patients with HSIL, major cervical surgery could be avoided if the methylation test was negative. Methylation testing, as well as dual-staining and diagnostics detecting the mRNA transcripts of highly oncogenic types of HPV, might be used in the future in the diagnosis of pre-cancerous conditions, mainly of the cervix, and in HPV-dependent cervical cancer screening. The methylation test may also be used in the diagnosis and identification of lesions within the cervical canal, including those located deep within the frontal crypts, not visible even during a professional colposcopic evaluation of the cervix. [ABSTRACT FROM AUTHOR]

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Knowing human papillomavirus (HPV) status has important consequences for treatment selection in oropharyngeal cancer. The gold standard is to perform a biopsy. The objective of this paper is to develop a new computed tomography (CT) radiomics-based non-invasive solution to HPV status determination and investigate if and how it can be a viable and accurate complementary technique. Two hundred thirty-eight patients' CT scans were normalized and resampled. One thousand one hundred forty-two radiomics features were obtained from the segmented CT scans. The number of radiomic attributes was decreased by applying correlation coefficient analysis, backward elimination, and random forest feature importance analysis. Random over-sampling (ROSE) resampling algorithm was performed on the training set for data balancing, and as a result, 161 samples were obtained for each of the HPV classes of the training set. A random forest (RF) classification algorithm was used as a prediction model using five-fold cross-validation (CV). Model effectiveness was evaluated on the unused 20% of the imbalanced data. The applicability of the model was investigated based on previous research and error rates reported for biopsy procedures. The HPV status was determined with an accuracy of 91% (95% CI 83–99) and an area under the curve (AUC) of 0.77 (95% CI 65–89) on the test data. The error rates were comparable to those encountered in biopsy. As a conclusion, radiomics has the potential to predict HPV status with accuracy levels that are comparable to biopsy. Future work is needed to improve standardization, interpretability, robustness, and reproducibility before clinical translation. [ABSTRACT FROM AUTHOR]

Cervical cancer screening and human papillomavirus (HPV) vaccination are critical for those immunocompromised due to human immunodeficiency virus (HIV). Health education programs, including text messaging, can effectively improve knowledge of cervical cancer and recommended screening. This paper describes the data-driven development of a 4-week text-messaging intervention to improve HPV and cervical cancer knowledge among women living with HIV (WLH). This study reports data from surveys (n  = 81; January 2020 to September 2021) and focus group discussions (FGDs, n  = 39; April–June 2020) conducted among WLH in the DC area. While most WLH revealed that their usual sources of health information were through in-person group sessions, they pointed out that these were impractical options due to the coronavirus 2019 pandemic. They noted that a text-messaging intervention was feasible and acceptable. FGD participants' responses structured around the Protection Motivation Theory constructs informed the text-messaging library, covering topics such as (I) understanding of cervical cancer and HPV, (II) cervical cancer prevention and (III) HPV self-sampling. The utilization of low-cost and easily accessible health education interventions, such as mobile-based text messaging, can effectively increase knowledge and awareness of cervical cancer in populations that have been historically difficult to access and during times when health services are disrupted such as during a global pandemic or public health emergency. [ABSTRACT FROM AUTHOR]

Certain viruses called tumor viruses or oncoviruses are capable to change the gene expression pattern of distinct human or animal cell types in tissue culture, resulting in uncontrolled proliferation as well as a change in the social behavior of the infected cells: the oncovirus-transformed, immortalized cells are capable to form malignant neoplasms in suitable animal models. At present, seven human viruses are categorized as causative agents of distinct human malignancies. The genomes of human tumor viruses, typically encode viral oncoproteins and non-translated viral RNAs that affect the gene expression pattern of their target cells or induce genetic and epigenetic alterations contributing to oncogenesis. Recently, the application of chromatin conformation capture technologies and threedimensional (3D) molecular imaging techniques revealed how the gene products or genomes of certain human tumor viruses interact with and induce alterations in the 3D host genome structure. This Mini Review aims to cover selected aspects of these developments. The papers, discussed briefly, describe how insertion of a novel viral binding site for the 3D genome organizer cellular protein CCCTC-binding factor (CTCF) into the DNA of T cells infected by human T-cell lymphotropic virus type 1 (HTLV-1) may contribute to lymphomagenesis, as well as how integration of high risk human papillomavirus genome into the host cell DNA may facilitate cervical carcinogenesis. Recent results regarding the interactions of cellular genomes with the episomal, chromatinized DNA genomes of oncogenic human herpesvirus, Epstein-Barr virus (EBV) will also be summarized, similarly to available data regarding contacts formed by episomal or integrated hepatitis B virus (HBV) DNA with host chromatin. Finally, a putative mechanism of hepatitis C virus (HCV) induced chromatin alterations will be presented, which may solve the riddle, how a cytoplasmic RNA virus without a viral oncogene could induce malingnant transfrormation of hepatocytes. [ABSTRACT FROM AUTHOR]

Background: Gut microbiome is a complex community of microbes present in the human gut and plays an important role in the occurrence and progression of colorectal cancer (CRC). However, the relationship between virus and CRC has not been fully understood. Objective: To explore the hot spots and research trends in the field of CRC and virus. Methods: By using the bibliometric analysis tool CiteSpace and based on the articles of the Web of Science Core Collection (WoSCC) database, the country, institution, highly cited literature, keywords and so on were visually analyzed. Results: A total of 356 research articles on CRC from 2001 to 2023 were thoroughly analyzed. The USA and China have made the largest contribution in the field of virus and CRC. The Helmholtz Association published the most papers. There were relatively few cooperations among institutions from different countries. The results of keyword cluster analysis proved that the literature on the relationship between human cytomegalovirus (CMV) and CRC was the most widely studied aspect in this field. "Gut microbiota," "inflammatory bowel disease," "hepatitis b virus," and "human papillomavirus infection" are the current research hotspots; "oncolytic virus," "apoptosis," and "gut microbiome" are the recent research frontiers and should be paid closer attention. Conclusion: By using CiteSpace bibliometric software, the visual analysis reflected the research trends and hot topics of virus and CRC. In addition, the prevalence and mechanism of specific virus on CRC were also reviewed, which provides valuable references for future CRC research. [ABSTRACT FROM AUTHOR]

Simple Summary: The association between HPV and cancer has been the focus of research, but there has been a lack of a comprehensive high-level evidence studies to systematically examine the relationship between them. Using Mendelian randomization, this paper provided an extensive analysis of the causal effect of HPV in cancer development. Our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The results of Mendelian randomization also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. Introduction: More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships. Methods: A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment. Results: Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. Conclusion: An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC)is the third most common cancer in the world and the second leading cause of cancer-related deaths, and over the past two decades, many of these researchers have provided a substantial amount of important information on the role of gut microbes in the development and progression of CRC. A causal relationship between the presence of specific microorganisms and CRC development has also been validated. Although a large number of papers related to this area have been published, no bibliometric study has been conducted to review the current state of research in this area and to highlight the research trends and hotspots in this area. This study aims to analyze the current status and future research trends of gut microbiota and CRC through bibliometric analysis. Methods: Publications from 2001 to 2022 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were used to visualize the research trends in this field, including the analysis of title, country, institution, author, number of publications, year of publication, number of citations, journal, and H-index. Results: A total of 863 studies were eventually identified, and the articles retrieved were cited an average of 44.85 times each. The number of publications on this topic has been increased steadily since 2011. China and the USA have made the largest contribution in the field. FRONTIERS IN MICROBIOLOGY is the top productive journal with 26 papers, and Gut journal has the highest average citation (167.23). Shanghai Jiao Tong University is the most contributive institution. Professor Yu J, Sung, Joseph J. Y and Fang JY are the most productive authors in this field. Keyword co-occurrence analysis showed that the terms of "'Gut Microbiota", "Colorectal Cancer", "Inflammation", "Probiotic" and "Fusobacterium Nucleatum" were the most frequent, which revealed the research hotpots and trends in this field. Conclusions: There has been a growing number of publications over the past two decades according to the global trends. China and the USA still maintained the leading position in this field. However, collaboration between institutions needs to be strengthened. It's commended to pay attention to the latest hotspots, such as "F. nucleatum" and "probiotics". This bibliometric analysis evaluates the scope and trends of gut microbiota and CRC, providing a useful perspective on current research and future directions for studying the link between the gut microbiota and CRC. [ABSTRACT FROM AUTHOR]

Cervical cancer ranks as the third most prevalent malignancy in women worldwide. The persistence of Human papillomavirus (HPV) infection stands out as the foremost risk factor for cervical cancer development. Among the numerous HPV subtypes, HPV16 infection emerges as the primary pathogenic determinant of cervical cancer. To date, no specific drugs have been approved. In this study, we engineered two high-affinity fusion protein targeting HPV16 L1 protein based on the alpaca-derived single-domain antibody 2C12 previously obtained in our laboratory. These two fusion proteins exhibited potent neutralizing activity against HPV16 pseudovirus with IC50 values of 7.8 nM and 6.5 nM, respectively. Molecular docking analysis revealed that 2C12 formed ten pairs of hydrogen bonds with HPV16 L1, among which Arg39 and Thr100 established multiple pairs of hydrogen bonds with HPV16 L1, indicating their crucial roles in antigen-antibody binding process. These structural and biological findings underscore the effective binding capacity of these fusion proteins to HPV16, leading to reduced viral load and providing valuable insights into therapeutic antibody and vaccine development against HPV 16 infection. [ABSTRACT FROM AUTHOR]

Introduction: Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. Hypothesis: Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. Aims of the study and Methods: Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. Results: The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia's epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. Conclusion: This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology. [ABSTRACT FROM AUTHOR]

This post hoc analysis explored the age-specific risk of cervical precancer in women infected with human papillomavirus (HPV), using data from a cohort of 7263 participants aged 21-71years undergoing cervical screening. We found a slightly varied prevalence of high-risk HPV (hrHPV) in different age, with highest in women under 30 years old (9.28% for 13 hrHPVs tested by HC2-HPV, 10.82% for 14 hrHPVs tested by DH3-HPV). However, the prevalence of cytology abnormalities peaked in age 30–39 years (~ 3.6%). A total of 5840 women completed 3-year follow-up. Among them, 558 were positive for HC2 assay and 583 were positive for DH3-HPV at baseline. Of note, the 3-year cumulative risks for cervical intraepithelial neoplasia grade 2+ (CIN2+) or grade 3+ (CIN3+) in women infected with high-risk HPV did not increase with age but declined (e.g., 41.67%, 27.78%, 26.42%, 15.98%, and 18% for CIN2 + risk in HC2-positive women at year 25–29, year 30–39, year 40–49, year 50–59, and year 60–71, respectively). If stratified by the median age, younger women (25–48 years) positive with HC2-HPV at baseline had a higher 3-year CIN2+/CIN3 + risk than older women (49–71 years) [26.55% (95%CI = 21.8-31.92%) vs. 18.28% (95%CI = 14.11-23.34%), P = 0.019; 15.52% (95%CI = 11.81-20.14%) vs. 9.7% (95%CI = 6.71-13.83%), P = 0.039]. Similarly, for women positive with DH3-HPV at baseline, younger group had a higher 3-year CIN2+/CIN3 + risk than older group [26.44% (95%CI = 21.73-31.75%) vs. 17.01% (95%CI = 13.11-21.78%), P = 0.006; 15.25% (95%CI = 11.6-19.8%) vs. 9.03% (95%CI = 6.24-12.9%), P = 0.021]. These findings indicate the potential value of age-specific risk assessment in cervical cancer screening. [ABSTRACT FROM AUTHOR]

Cervical cancer is the 4th leading cause of tumor-related deaths among women, primarily due to high-risk Human Papillomavirus (HPV). The role of Collapsin Response Mediator Protein 4 (CRMP4) in cervical cancer remains poorly understood, despite its variable expression across various cancers. This study aimed to investigate the mechanisms by which CRMP4 regulates cervical cancer cell growth as well as Epithelial-Mesenchymal Transition (EMT). Based on transcriptome data from The Cancer Genome Atlas (TCGA), CRMP4 is significantly downregulated in cervical cancer tissues compared to normal tissues. Immunoblot assays revealed lower CRMP4 expression in cervical cancer cell lines. Cell Counting Kit-8 (CCK-8), colony formation and flowcytometry demonstrated that CRMP4 overexpression inhibited cell growth as well as stimulated apoptosis in HeLa as well as SiHa cells. In addition, CRMP4 overexpression increased Epithelial cadherin (E-cadherin) levels and decreased Neural cadherin (N-cadherin) and alpha-Smooth Muscle Actin (α-SMA) levels, indicating EMT suppression. CRMP4 overexpression downregulated the Wnt/β-catenin axis by reducing expressions of β- catenin, Wnt family member 3A (Wnt3a), c-Myc and cyclin D1. In summary, CRMP4 inhibits cervical cancer cell proliferation as well as EMT by mediating the Wnt/β-catenin axis. CRMP4 may therefore be a potential therapeutic target of cervical cancer. [ABSTRACT FROM AUTHOR]

This study aimed to examine the efficacy and safety of Modified Ermiao Granules in clearing high-risk human papillomavirus (HR-HPV) and reversing low-grade squamous intraepithelial lesions (LSIL), as well as to examine cervical tissues before and after drug treatment for absent in melanoma (AIM2) inflammasome-mediated pyroptosis. A total of 60 patients with persistent HR-HPV infection and cervical histopathology of the LSIL were randomly divided into control group and observation groups (n = 30 each). Observation group participants received Modified Ermiao Granules orally, whereas the control group received recombinant human interferon α2b vaginal effervescent tablets. After treatment, the observation group had a significantly lower HPV DNA loads than the control group (p < 0.05). Compared with the control group, the observation group had a significantly higher HR-HPV clearance rate (χ² = 4.267, p = 0.039). Accordingly, the LSIL reversal rates were 33.33% and 60.00% in the control and observation groups, respectively (χ² = 4.286, p = 0.038). Both treatments reduced clinical symptoms in patients with HR-HPV with LSIL, but the observation group showed greater improvement (p < 0.05). Control and observation groups expressed AIM2 protein positively at 36.67% and 66.37%, respectively (χ² = 5.406, p < 0.05). Caspase-1, gasdermin D (GSDMD), and interleukin (IL)-1β levels in vaginal douche were significantly higher in the observation group than in the control group (p < 0.05). There was a significant negative correlation between HPV DNA load and AIM2 expression in cervical tissues (rho = -0.493, p < 0.05), with caspase-1 (r = -0.439, p < 0.05), GSDMD (r = -0.508, p<0.05) and IL-1β levels (r = -0.347, p = 0.007) in vaginal douche. In conclusion, the Modified Ermiao Granules effectively cleared persistent HRHPV infections and reversed LSIL, which may be associated with its activating effect on AIM2 inflammasome-mediated pyroptosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers of the lip and oral cavity are common cancers worldwide. Up to 46% of oral cancers are preventable if risk factors are avoided and if precancerous lesions are detected at an early stage. To reduce the incidence of oral cancer and its mortality rate, there is ongoing research studying new diagnostic and treatment methods. This review aims to present a novel glance at oral cancer—its current classification and epidemiology—and will provide new insights into the development of new diagnostic methods and therapies of oral cancer. Oral cavity and lip cancers are the 16th most common cancer in the world. It is widely known that a lack of public knowledge about precancerous lesions, oral cancer symptoms, and risk factors leads to diagnostic delay and therefore a lower survival rate. Risk factors, which include drinking alcohol, smoking, HPV infection, a pro-inflammatory factor-rich diet, and poor oral hygiene, must be known and avoided by the general population. Regular clinical oral examinations should be enriched in an oral cancer search protocol for the most common symptoms, which are summarized in this review. Moreover, new diagnostic methods, some of which are already available (vital tissue staining, optical imaging, oral cytology, salivary biomarkers, artificial intelligence, colposcopy, and spectroscopy), and newly researched techniques increase the likelihood of stopping the pathological process at a precancerous stage. Well-established oral cancer treatments (surgery, radiotherapy, chemotherapy, and immunotherapy) are continuously being developed using novel technologies, increasing their success rate. Additionally, new techniques are being researched. This review presents a novel glance at oral cancer—its current classification and epidemiology—and will provide new insights into the development of new diagnostic methods and therapies. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) have a profound impact on sexual and reproductive health worldwide. Syphilis, gonorrhea, chlamydia, and trichomoniasis are four currently curable STIs. However, most STI cases are asymptomatic and not detected without laboratory diagnostics. Hepatitis B virus, herpes simplex virus, human immunodeficiency virus (HIV), and human papillomavirus (HPV) are four viral and incurable infections, but they can be mitigated by treatment. We investigated the prevalence of selected sexually transmitted pathogens and their relationship with HPV and HIV infection in women from Maputo, the capital of Mozambique. A cross-sectional study was conducted on 233 non-pregnant women seeking health care relating to gynecological symptoms in Mavalane Health facilities in Maputo, between the 1st of February 2018 and the 30th of July 2019. Cervical brush samples were collected and DNA was extracted. Selected STIs including HPV were detected using multiplex STD and HPV Direct Flow Chip Kits through a manual Hybrispot platform (Vitro, Master Diagnostica, Sevilla, Spain). HIV testing was performed using rapid tests: Determine HIV 1/2 test (Alere Abbott Laboratories, Tokyo, Japan) for screening, and UniGold HIV (Trinity Biotech, Ireland) for confirmation. All women (n = 233) were negative for Haemophilus ducreyi and Herpes Simplex Virus-1 (HSV-1). Among the 233 women, a high prevalence of STIs was found (89%), 63% of the women were positive for HPV and 24% were HIV positive. Treponema pallidum (TP), Trichomonas vaginalis (TV), Herpes Simplex Virus-2 (HSV-2), and Chlamydia trachomatis (CT) were detected in 17%, 14%, 8%, and 8% of the women, respectively. As a common phenomenon, vaginal discharge (90%) was the lower genital tract symptom reported by the majority of the women. Co-infection with any STI and HPV was detected in 56% (130/233) while 45% (59/130) of the co-infections were with high-risk HPV (hrHPV) genotypes. Among the HPV-positive participants, infection by TP was the most prevalent (27%). In total, 28% (66/233) of the participants were positive for any hrHPV genotypes. Co-infection with any STI and HIV was found in 15% (34/233) of the study participants. There was a significant association between HPV infection and TP (p = 0.039) and HSV-2 (p = 0.005). TV, TP, and CT-S1-CT-S2 positivity were significantly more prevalent in HIV-positive participants. Pathobionts Ureaplasma urealyticum/parvum and Mycoplasma hominis were detected in 84.0% (195/233) and 45% (105/233), respectively. This present study describes a high prevalence of STIs. Co-infection between HPV and STIs was found in the majority of the study subjects. The high prevalence of HPV emphasizes the need for HPV vaccination to prevent cervical cancer in this population. Management of STIs is also important in women presenting with gynecological symptoms. [ABSTRACT FROM AUTHOR]

The gastrointestinal and respiratory systems are closely linked in different ways, including from the embryological, anatomical, cellular, and physiological angles. The highest number (and various types) of microorganisms live in the large intestine/colon, and constitute the normal microbiota in healthy people. Adverse alterations of the microbiota or dysbiosis can lead to chronic inflammation. If this detrimental condition persists, a sequence of pathological events can occur, such as inflammatory bowel disease, dysplasia or premalignant changes, and finally, cancer. One of the most commonly identified bacteria in both inflammatory bowel disease and colon cancer is Escherichia coli. On the other hand, patients with inflammatory bowel disease are at risk of several other diseases—both intestinal (such as malnutrition and intestinal obstruction, besides cancer) and extraintestinal (such as arthritis, bronchiectasis, and cancer risk). Cancers of the lung and colon are the two most common malignancies occurring worldwide (except for female breast cancer). Like the bacterial role in colon cancer, many studies have shown a link between chronic Chlamydia pneumoniae infection and lung cancer. However, in colon cancer, genotoxic colibactin-producing E. coli belonging to the B2 phylogroup may promote tumorigenesis. Furthermore, E. coli is believed to play an important role in the dissemination of cancer cells from the primary colonic site. Currently, seven enteric pathogenic E. coli subtypes have been described. Conversely, three Chlamydiae can cause infections in humans (C. trachomatis may increase the risk of cervical and ovarian cancers). Nonetheless, striking genomic plasticity and genetic modifications allow E. coli to constantly adjust to the surrounding environment. Consequently, E. coli becomes resistant to antibiotics and difficult to manage. To solve this problem, scientists are thinking of utilizing suitable lytic bacteriophages (viruses that infect and kill bacteria). Several bacteriophages of E. coli and Chlamydia species are being evaluated for this purpose. [ABSTRACT FROM AUTHOR]

During the past two decades evidence has been developed that indicates a handful of viruses with known oncogenic capacity, have potential roles in breast cancer. These viruses are mouse mammary tumour virus (MMTV - the cause of breast cancer in mice), high-risk human papilloma viruses (HPV-the cause of cervical cancer), Epstein Barr virus (EBV-the cause of lymphomas and naso-pharyngeal cancer) and bovine leukemia virus (BLV - the cause of cancers in cattle). These viruses may act alone or in combination. Each of these viruses are significantly more prevalent in breast cancers than in normal and benign breast tissue controls. The odds ratios for the prevalence of these viruses in breast cancer compared to normal and benign breast controls, are based on case control studies - MMTV 13·40, HPV 5.56, EBV 4·43 and BLV 2·57. The odds ratios for MMTV are much greater compared to the other three viruses. The evidence for a causal role for mouse mammary tumour virus and high risk for cancer human papilloma viruses in human breast cancer is increasingly comprehensive. The evidence for Epstein Barr virus and bovine leukemia virus is more limited. Overall the evidence is substantial in support of a viral cause of breast cancer. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. Methods: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. Results: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. Conclusions: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3. [ABSTRACT FROM AUTHOR]

Background: Multifocal epithelial hyperplasia (MEH), or focal epithelial hypertension (FEH), or Heck's disease, is an uncommon, benign oral mucosal disease associated with human papillomavirus infection. It is mostly observed in indigenous populations of the world, and has been rarely reported in China. However, previous research suggested there might be a greater prevalence of MEH in the Chinese population. While predominantly involves the lips, buccal mucosa and tongue, MEH was occasionally reported to affect the hard palate and gingiva as well. Case presentation: This paper reports a case of extensive MEH lesions that confined to the interdental papilla of a Chinese male without detection of HPV, and summarizes the published gingiva-involved MEH reports from 1966 until present. The lesions were excised with an Er: YAG laser after scaling and root planning, no recurrence was observed after 6-month follow-up. Conclusions: The present report illustrates the need for clinicians to be aware of rare presentations of MEH to facilitate a prompt diagnosis and proper management. More reports are encouraged to determine a correct prevalence rate of MEH in China. [ABSTRACT FROM AUTHOR]

Papillomas are benign epithelial lesions protruding on the epithelial surfaces as finger-like or warty projections. These lesions are often caused by papillomavirus (PV) infection. Congenital papillomas have been reported in foals. However, to date, no evidence of PV infection has been provided. In the present paper, we describe the main clinical–pathological features of a congenital papilloma observed in a foal. In addition, biomolecular tests demonstrated BPV1 infection in the case under study. Such data stimulate further investigations, even on archived samples, aiming to clarifying the etiology of equine congenital papilloma and the clinical relevance, if any, of BPV1 vertical transmission in horses. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers are among the most common and lethal cancers worldwide. GI microbes play an important role in the occurrence and development of GI cancers. The common mechanisms by which GI microbes may lead to the occurrence and development of cancer include the instability of the microbial internal environment, secretion of cancer-related metabolites, and destabilization of the GI mucosal barrier. In recent years, many studies have found that the relationship between GI microbes and the development of cancer is closely associated with the GI redox level. Redox instability associated with GI microbes may induce oxidative stress, DNA damage, cumulative gene mutation, protein dysfunction and abnormal lipid metabolism in GI cells. Redox-related metabolites of GI microbes, such as short-chain fatty acids, hydrogen sulfide and nitric oxide, which are involved in cancer, may also influence GI redox levels. This paper reviews the redox reactions of GI cells regulated by microorganisms and their metabolites, as well as redox reactions in the cancer-related GI microbes themselves. This study provides a new perspective for the prevention and treatment of GI cancers. [ABSTRACT FROM AUTHOR]

The paper deals with the evaluation of the performance of an existing and previously validated CT based radiomic signature, developed in oropharyngeal cancer to predict human papillomavirus (HPV) status, in the context of anal cancer. For the validation in anal cancer, a dataset of 59 patients coming from two different centers was collected. The primary endpoint was HPV status according to p16 immunohistochemistry. Predefined statistical tests were performed to evaluate the performance of the model. The AUC obtained here in anal cancer is 0.68 [95% CI (0.32–1.00)] with F1 score of 0.78. This signature is TRIPOD level 4 (57%) with an RQS of 61%. This study provides proof of concept that this radiomic signature has the potential to identify a clinically relevant molecular phenotype (i.e., the HPV-ness) across multiple cancers and demonstrates potential for this radiomic signature as a CT imaging biomarker of p16 status. [ABSTRACT FROM AUTHOR]

Viruses infect millions of people worldwide each year, and some can lead to cancer or increase the risk of cancer. As viruses have highly mutable genomes, new viruses may emerge in the future, such as COVID-19 and influenza. Traditional virology relies on predefined rules to identify viruses, but new viruses may be completely or partially divergent from the reference genome, rendering statistical methods and similarity calculations insufficient for all genome sequences. Identifying DNA/RNA-based viral sequences is a crucial step in differentiating different types of lethal pathogens, including their variants and strains. While various tools in bioinformatics can align them, expert biologists are required to interpret the results. Computational virology is a scientific field that studies viruses, their origins, and drug discovery, where machine learning plays a crucial role in extracting domain- and task-specific features to tackle this challenge. This paper proposes a genome analysis system that uses advanced deep learning to identify dozens of viruses. The system uses nucleotide sequences from the NCBI GenBank database and a BERT tokenizer to extract features from the sequences by breaking them down into tokens. We also generated synthetic data for viruses with small sample sizes. The proposed system has two components: a scratch BERT architecture specifically designed for DNA analysis, which is used to learn the next codons unsupervised, and a classifier that identifies important features and understands the relationship between genotype and phenotype. Our system achieved an accuracy of 97.69% in identifying viral sequences. [ABSTRACT FROM AUTHOR]

Objective: To understand the effect of changing from cytology‐based to primary HPV screening on the positive predictive value (PPV) of colposcopy referrals for cervical intraepithelial neoplasia (CIN) in a cohort offered HPV vaccination. Design: Retrospective pre/post observational cohort study. Setting: Scotland. Population or sample: 2193 women referred to colposcopy between September 2019 and February 2020 from cytology‐based screening and between September 2020 and February 2021 from primary high‐risk HPV (hrHPV) screening. Methods: Calculating positive predictive values (PPVs) for two cohorts of women; one having liquid‐based cytology screening and the other, the subsequent hrHPV cervical screening as a pre/post observational study. Main outcome measures: Positive predictive values of LBC and hrHPV cut‐offs for colposcopy referral for CIN at colposcopy. Results: Three papers fitted our criteria; these reported results only for cytology‐based screening. The PPV was lower for women in HPV‐vaccinated cohorts indicating a lower prevalence of disease. Vaccination under the age of 17 had the lowest PPV reported. Scottish colposcopy data concerning hrHPV and cytology showed a non‐significant difference between PPV (17.5%, 95% CI 14.3–20.7, and 20.6, 95% CI 16.7–24.5, respectively) for referrals with a cut‐off of low grade dyskaryosis (LGD); both met the standard set of 8–25%. The hrHPV PPV (66.7, 95% CI 56.8–76.6) was comparable to cytology (64.1, 95% CI 55.8–72.4) for referrals with a cut‐off of high grade dyskaryosis (HGD) but neither met the standard set of 77–92%. Conclusions: Current literature only provides PPVs for LBC and, overall, the vaccinated cohort had lower PPVs. Only LG dyskaryosis met PHE criteria. The PPV for HPV‐vaccinated women undergoing either LBC or HR‐HPV screening were not statistically different. However, similar to papers in the current literature, HG dyskaryosis (HGD) PPVs of both techniques did not meet the PHE threshold of 76.6–91.6% outlined in the cervical standards data report. [ABSTRACT FROM AUTHOR]

Objective: The UK incidence of oropharyngeal cancer has risen sharply over the last 30 years with an increase in human papillomavirus (HPV) associated diagnoses, most prevalent in younger, working age populations. This meta‐ethnography explores the psychosocial needs of HPV+ve oropharyngeal cancer patients during early recovery following (chemo)radiotherapy. Methods: Meta‐ethnography methods were used, based on the approach of Noblit and Hare. Systematic searches for relevant qualitative studies were conducted in five electronic databases (MEDLINE, PubMed, CINAHL, PsycINFO and Cochrane database) between 2010 and 2021, followed by citation searching. Results: Twenty‐three papers exploring the psychosocial needs of HPV+ve oropharyngeal cancer patients after treatment were included. Findings were synthesised to develop five constructs: 'gaps in continuity of support from healthcare professionals' reflecting unmet needs; 'changes to self‐identity' revealing the comprehensive disruption of this disease and treatment; 'unrealistic expectations of recovery' highlighting the difficulty of preparing for the impact of treatment; 'finding ways to cope' describing the distinct complexity of this experience; and 'adjusting to life after the end of treatment' exploring how coping strategies helped patients to regain control of their lives. Conclusions: Completing (chemo)radiotherapy signalled a transition from hospital‐based care to home‐based support, challenging patients to address the constructs identified. An unexpectedly difficult and complex recovery meant that despite a favourable prognosis, poor psychosocial well‐being may threaten a successful outcome. The provision of tailored support is essential to facilitate positive adjustment. [ABSTRACT FROM AUTHOR]

The Ministry of Health Malaysia aims to fully replace liquid-based cytology (LBC) with Human Papillomavirus (HPV) tests and increase the screening coverage from a baseline of 25% to 40% by 2023, followed by a 10% yearly increment until 70% coverage. This transition requires proper planning, including the number of tests needed and budget allocation. This study aims to simulate different transition strategies involving the shift from LBC to HPV testing with expanded screening coverage to predict their impact on cervical cancer elimination in Malaysia. A system dynamics model was developed to simulate the transition from LBC to HPV testing and HPV vaccination coverage in Malaysia. The dynamic model utilised local epidemiological data, published research, and expert opinion when data was unavailable. The simulation showed that a combination of high HPV vaccination coverage and transitioning fully to five-yearly HPV testing by 2030, coupled with a 70% screening uptake by 2040, would accelerate cancer elimination in Malaysia by 18 years with an estimated screening cost of MYR1.81 billion equivalent to USD 411 millions compared to the baseline of using LBC as the primary screening method (MYR1.39 billion, USD 315 millions). Sustained, it would lead to averting 6,000 new cancer cases by 2070. Alternatively, conducting HPV screenings twice before age 50 would advance cervical cancer elimination by 14 years and prevent approximately 1000 new cases by 2070, with an estimated cost of MYR1.13 billion equivalent to USD 257 millions. A delay in achieving the full transition prolonged the elimination more than a delay in increasing the screening coverage. In all scenarios, yearly vaccination of 90% of girls age 13 is crucial to achieving elimination. In the Malaysian context, where HPV vaccination coverage has reached considerable levels, the evidence advocates for a full transition from LBC to HPV testing, ideally by 2030. While expanding screening coverage remains a critical factor in this endeavour, the findings unequivocally endorse prioritising the transition process. Trial registration: Trial registration number: NMRR ID-22-00187-DJU. [ABSTRACT FROM AUTHOR]

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Background: Both the high-risk human papillomavirus (HR-HPV) infection and tobacco exposure are significantly associated with cervical neoplasm risk. Immune cells play important roles in carcinogenesis. However, it is still unclear whether immune cells have a mediating effect on the HR-HPV infection and tobacco exposure with cervical neoplasm development. Aim: The aim of this study was to determine how the increased white blood cell (WBC) count affects the relationship between HR-HPV DNA load and tobacco exposure in the development of cervical neoplasia. Methods: A hospital-based case–control study design was conducted with a total of 108 cases of Taiwanese women with ≥ cervical intraepithelial neoplasia (CIN) I confirmed by biopsy, and 222 healthy Taiwanese female subjects with negative findings on a Pap smear were assigned to the control group. The study evaluated HR-HPV status and immune cell counts (WBCs, natural killer (NK) cells) and tobacco exposure by a self-construct questionnaire. Results: Both HR-HPV DNA load and tobacco exposure significantly independently increased cervical neoplasm risk (AORs: 1.28 and 1.42, respectively). Similar significant results were found for WBCs and NK cells, with respective AORs of 1.20 and 1.00. Moreover, increased WBCs (β = 0.04, 95% CI corrected: 0.01–0.07) and tobacco exposure (β = 0.02, 95% CI corrected: 0.01–0.04) mediated the relationship between the high-risk HPV DNA load and cervical neoplasm risk. Conclusions: Elevated WBC count acts as both predictor and mediator in cervical neoplasm development linked to HR-HPV DNA load. Monitoring and maintaining WBC levels within the normal range could be a preventive strategy for cervical neoplasm development. [ABSTRACT FROM AUTHOR]

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate HR-HPV infections in women with a double cervix within the National Cervical Cancer Screening program of the Lazio region (Italy). From June 2021 to March 2024, a total of 142,437 samples were analyzed by Seegene's Anyplex TM II HR-HPV method, which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervices and analyzed separately. Twenty-seven women with a double cervix were identified (0.019%): 23 women were tested as negative for both cervices, while the remaining four (namely A, B, C, and D) resulted positive. By genotyping, the following results were obtained: (A) Both samples showed genotype 31; (B) one cervix was negative while the other showed genotype 58; (C) one cervix was positive for HPV 18 and 31 while for 18, 31, and 33 in the other; and (D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition where the presence of HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of oropharyngeal cancer (OPC) is increasing. This study used bibliometric analysis and topic modeling to explore the research trends and advancements in this disease over the past 10  years, providing valuable insights to guide future investigations. Methods: 7,355 English articles from 2013 to 2022 were retrieved from the Web of Science Core Collection for bibliometric analysis. Topic modeling was applied to 1,681 articles from high-impact journals, followed by an assessment of topic significance ranking (TSR). Medical Subject Headings (MeSH) terms were extracted using R and Python, followed by an analysis of the terms associated with each topic and on an annual basis. Additionally, genes were extracted and the number of genes appearing each year and the newly emerged genes were counted. Results: The bibliometric analysis suggested that the United States and several European countries hold pivotal positions in research. Current research is focused on refining treatments, staging and stratification. Topic modeling revealed 12 topics, emphasizing human papillomavirus (HPV) and side effect reduction. MeSH analysis revealed a growing emphasis on prognosis and quality of life. No new MeSH terms emerged after 2018, suggesting that the existing terms have covered most of the core concepts within the field of oropharyngeal cancers. Gene analysis identified TP53 and EGFR as the most extensively studied genes, with no novel genes discovered after 2019. However, CD69 and CXCL9 emerged as new genes of interest in 2019, reflecting recent research trends and directions. Conclusion: HPV-positive oropharyngeal cancer research, particularly treatment de-escalation, has gained significant attention. However, there are still challenges in diagnosis and treatment that need to be addressed. In the future, more research will focus on this issue, indicating that this field still holds potential as a research hotspot. [ABSTRACT FROM AUTHOR]

The Cervical Screening Cohort enrols women screened for human papillomavirus (HPV) and cervical abnormalities within the capital region of Sweden from the organised screening program and the non-organised testing of cervical samples. The cohort started in 2011 and has enrolled more than 670,000 women, contributing with more than 1.2 million biobanked samples. The cohort is systematically updated with individual-level data from the Swedish National Cervical Screening Registry (NKCx). Key variables include birthdate, sampling date, cytological, histopathological and HPV analysis results, and invitation history. Each sampling and subsequent clinical follow-up is sequentially registered, allowing for longitudinal analyses of screening results and associated results of the clinical workup. The cohort is ideal for longitudinal, long-term follow-up studies due to its validated documentation and registry-derived information. From the data, it is possible to penetrate important human health mechanisms. The data are available as open-data and GDPR-compliant. Samples are available after getting the required permissions. Results will help researchers understand factors that increase cancer risk and other diseases. [ABSTRACT FROM AUTHOR]

Background: The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically. Methods: Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China's National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed. Results: A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively. Conclusion: HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. Methods: A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. Results: A total of 171 participants with a median (interquartile range) age of 40 (31–50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. Conclusion: These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities. [ABSTRACT FROM AUTHOR]

Objectives: Human papillomavirus (HPV) primary testing for cervical screening is being implemented around the world. We explored HPV awareness, and knowledge about primary screening in Great Britain (England, Scotland and Wales), where it has been in place for several years, ahead of extended screening intervals being implemented in England. Setting/Methods: Women aged 18–70 (n = 1995) were recruited by YouGov from their online panel in August 2022. The weighted sample (n = 1930) was population-representative by age, region, education and social grade. We measured HPV awareness, knowledge (excluding those unaware of HPV) using eight true/false items, and understanding of the role of HPV testing in cervical screening. Results: Overall, 77.6% (1499/1930) of women were aware of HPV. When asked to identify the statement describing how cervical screening works, only 12.2% (236/1930) correctly selected the statement reflecting HPV primary screening (13.5% (194/1436) in screening-eligible women). Excluding those unaware of HPV, most participants had heard about the virus in the context of cervical screening (981/1596; 61.5%) or HPV vaccination (1079/1596; 67.6%). Mean knowledge score was 3.7 out of 8 (SD = 2.2) in this group. Most knew that an HPV-positive result does not mean a woman will definitely develop cervical cancer (1091/1499; 72.8%) but far fewer were aware of the long timeline for HPV to develop into cervical cancer (280/1499; 18.7%). Conclusions: Only three-quarters of women in Britain are aware of HPV, and knowledge of primary screening is very low, even among screening-age women. This points to continued need for awareness-raising campaigns to ensure informed choice about screening and mitigate public concern when screening intervals are extended. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth most diagnosed cancer and the fourth leading cause of cancer death in women globally. Its onset and progression have been attributed to high-risk human papillomavirus (HPV) types, especially 16 and 18, while the Epstein–Barr virus (EBV) is believed to also significantly contribute to cervical cancer growth. The E6 protein associated with high-risk HPV strains, such as HPV16 and HPV18, is known for its role in promoting cervical cancer and other anogenital cancers. E6 proteins contribute to the malignant transformation of infected cells by targeting and degrading tumor suppressor proteins, especially p53. On the other hand, EBV nuclear antigen 1 (EBNA1) plays a crucial role in the maintenance and replication of the EBV genome in infected cells. EBNA1 is believed to increase HPV E6 and E7 levels, as well as c-MYC, and BIRC5 cellular genes in the HeLa cell line, implying that HPV/EBV co-infection accelerates cervical cancer onset and growth. Thus, the E6 and EBNA1 antigens of HPV and EBV, respectively, are attractive targets for cervical cancer immunotherapy. This study, therefore, virtually screened for potential drug candidates with good binding affinity to all three oncoviral proteins, HPV16 E6, HPV18 E6, and EBNA1. The compounds were further subjected to ADMET profiling, biological activity predictions, molecular dynamics (MD) simulations, and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations. A total of six compounds comprising ZINC000013380012, ZINC000070454124, ZINC000014588133, ZINC000085568136, ZINC000095909247, and ZINC000085597263 demonstrated very strong affinity (≤−60 kJ/mol) to the three oncoviral proteins (EBNA1, HPV16 E6, and HPV18 E6) after being subjected to docking, MD, and MM/PBSA. These compounds demonstrated relatively stronger binding than the controls used, inhibitors of EBNA1 (VK-1727) and HPV E6 (baicalein and gossypetin). Biological activity predictions also corroborated their antineoplastic, p53-enhancing, Pin1 inhibitory, and JAK2 inhibitory activities. Further experimental testing is required to validate the ability of the shortlisted compounds to silence the insidious effects of HPV E6 and EBNA1 proteins in cervical cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Our understanding of the underlying biology of proton therapy in head and neck cancers is limited. Here, we assessed the proton therapy-related radiobiological processes in head and neck cancer cells. We showed that proton therapy resulted in biological effects similar to those of classical photon-based radiotherapy. Photon-based radiotherapy (XRT) is one of the most frequently used treatment modalities for HPV-negative and HPV-positive locally advanced head and neck squamous cell carcinoma (HNSCC). However, locoregional recurrences and normal RT-associated toxicity remain major problems for these patients. Proton therapy (PT), with its dosimetric advantages, can present a solution to the normal toxicity problem. However, issues concerning physical delivery and the lack of insights into the underlying biology of PT hamper the full exploitation of PT. Here, we assessed the radiobiological processes involved in PT in HPV-negative and HPV-positive HNSCC cells. We show that PT and XRT activate the DNA damage-repair and stress response in both HPV-negative and HPV-positive cells to a similar extent. The activation of these major radiobiological mechanisms resulted in equal levels of clonogenic survival and mitotic cell death. Altogether, PT resulted in similar biological effectiveness when compared to XRT. These results emphasize the importance of dosimetric parameters when exploiting the potential of increased clinical effectiveness and reduced normal tissue toxicity in PT treatment. [ABSTRACT FROM AUTHOR]

Endometriosis is a common gynaecological condition, with a long diagnostic delay. Surgery is required to confirm a diagnosis, highlighting the need for a non‐invasive biomarker. Extracellular vesicles (EVs) may have a role in endometriosis pathogenesis, yet there is limited EV biomarker literature available. This study aimed to investigate the feasibility of isolating cervico‐vaginal fluid EVs sampled using cervical brushes and vaginal swabs and to compare these methods. After providing informed consent, patients undergoing surgery for suspected endometriosis had cervical brush and vaginal swab samples collected under general anaesthetic. Isolated EVs were characterised through negative stain transmission electron microscopy (TEM), Western blotting (TSG101, CD63, Calnexin, ApoB, Albumin), tunable resistive pulse sensing (TRPS), microBCA assays and RT‐qPCR of miRNAs. PCR was performed on samples prior to EV isolation to assess bacteria present in samples. Cervical brush and vaginal swab EVs were intact vesicles with limited co‐isolated contaminants. Cervical brushes had higher concentrations of particles compared to match vaginal swabs, although both samples had low concentrations. Protein and miRNA yield were similar between matched samples. PCR demonstrated only a small amount DNA within samples was bacterial (>0.5%). Cervico‐vaginal fluids EVs were successfully isolated from cervical brushes and vaginal swabs, demonstrating a new method of sampling reproductive EVs. EV yield from both sample types was low. Similar protein and miRNA levels suggest either sampling method may be suitable for biomarker studies. [ABSTRACT FROM AUTHOR]

The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide. [ABSTRACT FROM AUTHOR]

Coriolus versicolor (CV) is a common species from the Polyporaceae family that has been used in traditional Chinese herbal medicine for over 2000 years. Among well-described and most active compounds identified in CV are polysaccharopeptides, such as polysaccharide peptide (PSP) and Polysaccharide-K (PSK, krestin), which, in some countries, are already used as an adjuvant agent in cancer therapy. In this paper, research advances in the field of anti-cancer and anti-viral action of CV are analyzed. The results of data obtained in in vitro and in vivo studies using animal models as well as in clinical research trials have been discussed. The present update provides a brief overview regarding the immunomodulatory effects of CV. A particular focus has been given to the mechanisms of direct effects of CV on cancer cells and angiogenesis. A potential use of CV compounds in anti-viral treatment, including therapy against COVID-19 disease, has also been analyzed based on the most recent literature. Additionally, the significance of fever in viral infection and cancer has been debated, providing evidence that CV affects this phenomenon. [ABSTRACT FROM AUTHOR]

Simple Summary: p16 IHC is the HPV detection method suggested by the current version of the TNM (AJCC 8th edition) for oropharyngeal squamocellular carcinoma. However, its reliability has been extensively discussed, and its applicability in every context, especially the enrollment of patients in de-intensification protocols, is debatable. Here, we discuss its limits, especially in populations with a low prevalence of HPV-driven oropharyngeal squamocellular carcinoma, and suggest the possible actions to be taken to overcome such limitations. High-risk human papillomavirus (HPV) infection is a defined etiopathogenetic factor in oropharyngeal carcinogenesis with a clear prognostic value. The P16 IHC (immunohistochemistry) is a widely accepted marker for HPV-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC); in the present paper, we discuss its reliability as a standalone marker in different populations. The literature suggests that rates of p16 IHC false positive results are inversely correlated with the prevalence of HPV-driven carcinogenesis in a population. We propose a formula that can calculate such a false positive rate while knowing the real prevalence of HPV-driven OPSCCs in a given population. As it has been demonstrated that p16 positive/HPV negative cases (i.e., false positives at p16 IHC) have the same prognosis as p16 negative OPSCC, we conclude that despite the valuable prognostic value of p16 IHC, relying only on a p16 IHC positive result to recommend treatment de-intensification could be risky. For this aim, confirmation with an HPV nucleic acid detection system, especially in areas with a low prevalence of HPV-related OPSCCs, should be pursued. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to highlight the key studies that have led to the current understanding and treatment of head and neck cancer. Method: The Thomson Reuters Web of Science database was used to identify relevant manuscripts. The results were ranked according to the number of citations. The 100 most cited papers were analysed. Results: A total of 63 538 eligible papers were returned. The median number of citations was 626. The most cited paper compared radiotherapy with and without cetuximab (3205 citations). The New England Journal of Medicine had the most citations (23 514), and the USA had the greatest number of publications (n = 66). The most common topics of publication were the treatment (n = 45) and basic science (n = 19) of head and neck cancer, followed by the role of human papillomavirus (n = 16). Conclusion: This analysis highlighted key articles that influenced head and neck cancer research and treatment. It serves as a guide as to what makes a 'citable' paper in this field. [ABSTRACT FROM AUTHOR]

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Cervical cancer is a significant global health issue primarily caused by high-risk types of human papillomavirus (HPV). Recent studies have reported an association between Trichomonas vaginalis (T. vaginalis) infections and HPV infections, highlighting the importance of simultaneously detecting these pathogens for effective cervical cancer risk management. However, current methods for detecting both T. vaginalis and HPV are limited. In this study, we present a novel approach using a microfluidic-chip-based system with loop-mediated isothermal amplification (LAMP) for the rapid and parallel detection of T. vaginalis, HPV16, HPV18, and HPV52 in a reagent-efficient and user-friendly manner. Compared to conventional LAMP assays in tubes, our system exhibits enhanced sensitivity with values of 2.43 × 101, 3.00 × 102, 3.57 × 101, and 3.60 × 102 copies per reaction for T. vaginalis, HPV16, HPV18, and HPV52, respectively. Additionally, we validated the performance of our chip by testing 47 clinical samples, yielding results consistent with the diagnostic methods used by the hospital. Therefore, our system not only offers a promising solution for concurrent diagnosis of T. vaginalis and HPV infections, particularly in resource-limited areas, due to its cost-effectiveness, ease of use, and rapid and accurate detection performance, but can also contribute to future research on the co-infection of these two pathogens. Moreover, the system possesses the capability to simultaneously detect up to 22 different types of pathogens, making it applicable across a wide range of domains such as diagnostics, food safety, and water monitoring. [ABSTRACT FROM AUTHOR]