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Cancers Oct 2023More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on...
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.
PubMed: 37958321
DOI: 10.3390/cancers15215147 -
Molecular Aspects of Medicine Dec 2023Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions... (Review)
Review
Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions to cancers of the cervix, head and neck, anus, vagina, vulva, and penis. Prophylactic vaccination programs, primarily targeting adolescent girls, have achieved dramatic reductions in rates of HPV infection and cervical cancer in recent years. However, there is a clear demand for a strategy to manage the needs of the many people who are already living with persistent HPV infection and/or HPV-associated conditions. Unlike prophylactic vaccines, which act to prevent HPV infection, therapeutic vaccination presents an opportunity to induce cellular immunity against established HPV infections and lesions and prevent progression to cancer. Several HPV vaccines are undergoing clinical development, using a range of platforms. Peptide- or protein-based vaccines, vector-based vaccines, whole-cell vaccines, and nucleic acid vaccines each offer relative merits and limitations for the delivery of HPV antigens and the subsequent generation of targeted immune responses. There has been particular interest in DNA-based vaccines, which elicit both cellular and humoral immune responses to provide long-lasting immunity. DNA vaccines offer several practical advantages over other vaccine platforms, including the potential for rapid and scalable manufacturing, targeting of many different antigens, and potential for repeat boosting. Furthermore, unlike vectored approaches, DNA vaccines are thermostable over extended time periods, which may enable shipping and storage. Several delivery strategies are available to address the main challenge of DNA vaccines, namely their relatively low transfection efficiency. We review the latest clinical data supporting the development of DNA vaccines and reflect on this exciting prospect in the management of HPV-related disease.
Topics: Male; Female; Adolescent; Humans; Papillomavirus Infections; Vaccines, DNA; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Human Papillomavirus Viruses
PubMed: 37931422
DOI: 10.1016/j.mam.2023.101224 -
Pathogens (Basel, Switzerland) Nov 2023Human papillomavirus (HPV) is implicated in over 90% of cervical cancer cases, with factors like regional variability, HPV genotype, the population studied, HPV... (Review)
Review
Human papillomavirus (HPV) is implicated in over 90% of cervical cancer cases, with factors like regional variability, HPV genotype, the population studied, HPV vaccination status, and anatomical sample collection location influencing the prevalence and pathology of HPV-induced cancer. HPV-16 and -18 are mainly responsible for the progression of several cancers, including cervix, anus, vagina, penis, vulva, and oropharynx. The oncogenic ability of HPV is not only sufficient for the progression of malignancy, but also for other tumor-generating steps required for the production of invasive cancer, such as coinfection with other viruses, lifestyle factors such as high parity, smoking, tobacco chewing, use of contraceptives for a long time, and immune responses such as stimulation of chronic stromal inflammation and immune deviation in the tumor microenvironment. Viral evasion from immunosurveillance also supports viral persistence, and virus-like particle-based prophylactic vaccines have been licensed, which are effective against high-risk HPV types. In addition, vaccination awareness programs and preventive strategies could help reduce the rate and incidence of HPV infection. In this review, we emphasize HPV infection and its role in cancer progression, molecular and immunopathogenesis, host immune response, immune evasion by HPV, vaccination, and preventive schemes battling HPV infection and HPV-related cancers.
PubMed: 38133265
DOI: 10.3390/pathogens12121380 -
International Journal of Clinical... Aug 2023Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These... (Review)
Review
Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These cancers claim > 400,000 lives annually. The persistent infection of HPV and the function of viral oncogenes are the primary causes of HPV-related cancers. However, only some HPV-infected persons or infected lesions will progress to cancer, and the burden of HPV-associated cancer varies widely according to gender and the part of the body infected. The dissimilarity in infection rates at different sites can explain only a small part of the differences observed. Much responsibility likely sits with contributions of specific epithelial cells and the cellular microenvironment at infected sites to the process of malignant transformation, both of which affect the regulation of viral gene expression and the viral life cycle. By understanding the biology of these epithelial sites, better diagnosis/treatment/management of HPV-associated cancer and/or pre-cancer lesions will be provided.
Topics: Male; Female; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Neoplasms; Carcinogenesis; Papillomaviridae; Uterine Cervical Neoplasms; Tumor Microenvironment
PubMed: 37199886
DOI: 10.1007/s10147-023-02340-y -
The Oncologist Jun 2024Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these... (Review)
Review
Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these viruses is common and usually cleared within 2 years. Only infections that become persistent are associated with the development of cancer, often occurring several decades later. These cancers mostly arise in 6 different anatomical regions: 5 are anogenital (anus, cervix, penis, vagina, and vulva) and the sixth is the oropharynx. Oncogenic HPVs promote cellular proliferation and genomic instability, but the anatomical niche of the target tissue also plays an important role in the development of cancer. Cells that reside in transitional regions between different types of epithelia, such as in the anus, cervix, and oropharynx, are particularly vulnerable to oncogenesis.
Topics: Humans; Papillomavirus Infections; Female; Male; Papillomaviridae; Neoplasms; Persistent Infection
PubMed: 38630576
DOI: 10.1093/oncolo/oyae071 -
Clinical Laboratory Aug 2023The aim was to discover the infectivity characteristics of recurrent vulvovaginal candidiasis (RVVC) in Chengdu, Sichuan Province, and provide a reference for RVVC...
BACKGROUND
The aim was to discover the infectivity characteristics of recurrent vulvovaginal candidiasis (RVVC) in Chengdu, Sichuan Province, and provide a reference for RVVC clinical diagnosis and treatment.
METHODS
The clinical data of 500 patients with RVVC were retrospectively analyzed, including life history, clinical symptoms, combined gynecological diseases, age, and distribution of pathogenic fungi, and the in vitro drug sensitivity of isolated fungi to antifungal drugs was assessed.
RESULTS
Among the 500 patients with RVVC, 486 (97.20%) had a sexual history, and the main clinical symptoms were vulva pruritus (394, 78.80%) and abnormal discharge (232, 46.40%). Common gynecological diseases were cervicitis (156 patients, 31.20%), human papillomavirus infection (130 patients, 26.00%), and coinfection with oth-er pathogens (127 patients, 25.40%). The high-incidence population was mainly concentrated in the 31 to 40-year-old age group, followed by the 20 to 30- and 41 to 50-year-old age groups. The number of patients gradually increased with time. Fungal culture was dominated by Candida albicans (69.80%), followed by Candida glabrata (28.40%), and Candida cerevisiae (0.60%). In vitro susceptibility testing showed that the highest drug resistance rate to antifungal drugs was to terbinafine (96.40%), followed by voriconazole (32.00%), fluconazole (26.40%), and itraconazole (17.40%), whereas the drug resistance rates to 5-fluorocytosine, caspofungin, amphotericin B, and micafungin were relatively low (1.80%, 0.60%, 0.40%, and 0.00%, respectively); the drug resistance rate to azoles gradually increased with age.
CONCLUSIONS
The occurrence of RVVC is closely related to sexual history. The most common cases are in women of childbearing age aged 20 - 50. The main pathogen is C. albicans, and the resistance rate to common azole antifungal drugs is increasing over time.
Topics: Humans; Female; Antifungal Agents; Candidiasis, Vulvovaginal; Retrospective Studies; Microbial Sensitivity Tests; Drug Resistance, Fungal; Candida albicans; Communicable Diseases
PubMed: 37560852
DOI: 10.7754/Clin.Lab.2023.230304 -
Human Vaccines & Immunotherapeutics Dec 2023Human papillomavirus (HPV) infection is associated with the risk of developing certain cancers, including cancers of the cervix, vulva, vagina, penis, anus, rectum, and...
Human papillomavirus (HPV) infection is associated with the risk of developing certain cancers, including cancers of the cervix, vulva, vagina, penis, anus, rectum, and oropharynx. In 2016, the bivalent HPV-16/18 vaccine was included in the Korea National Immunization Program. This vaccine protects against HPV types 16 and 18 and other oncogenic HPV types predominant in cervical and anal cancers. This post-marketing surveillance (PMS) study assessed the safety of the HPV-16/18 vaccine in Korea. The study was conducted in males and females aged between 9 and 25 years, from 2017 to 2021. Safety was measured in terms of frequency and intensity of adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) after each vaccine dose. The safety analysis included all participants who were vaccinated as per prescribing information and who completed a 30-day follow-up after at least one dose. Data were collected using individual case report forms. The total safety cohort included 662 participants. A total of 220 AEs were reported in 144 subjects (21.75%), and there were 158 ADRs in 111 subjects (16.77%), with the most common being injection site pain in all cases. No SAEs or serious ADRs were reported. Most AEs were reported after the first dose and were injection site reactions with mild intensity that recovered. No individuals required hospitalization or an emergency department visit. Safety results showed that the HPV-16/18 vaccine was generally well tolerated in the Korean population, and no safety concerns were identified.ClinicalTrials.gov Identifier: NCT03671369.
Topics: Male; Female; Humans; Child; Adolescent; Young Adult; Adult; Human papillomavirus 16; Uterine Cervical Neoplasms; Papillomavirus Infections; Human papillomavirus 18; Papillomavirus Vaccines; Drug-Related Side Effects and Adverse Reactions; Injection Site Reaction; Product Surveillance, Postmarketing; Republic of Korea
PubMed: 36896702
DOI: 10.1080/21645515.2023.2184756 -
Acta Obstetricia Et Gynecologica... Jan 2024Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the...
INTRODUCTION
Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the other without HPV infection (HPV-independent) often involving TP53 mutation. HPV-associated VSCC generally has a better progression-free survival than HPV-independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC.
MATERIAL AND METHODS
Immunohistochemistry for p53, Ki67 and p16 (a surrogate marker for HPV infection) was performed on formalin-fixed paraffin-embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi-square test and multivariable Cox regression model were used to investigate the association of different parameters with progression-free survival and disease-specific survival (DSS), and Kaplan-Meier curves were used to show the association of different parameters with survival.
RESULTS
The results of p53 and p16 immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression-free survival (p = 0.024) after adjustment for FIGO stage. p16 immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression-free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders.
CONCLUSIONS
p53 and p16 immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.
Topics: Female; Humans; Prognosis; Human Papillomavirus Viruses; Papillomavirus Infections; Retrospective Studies; Cyclin-Dependent Kinase Inhibitor p16; Tumor Suppressor Protein p53; Carcinoma, Squamous Cell; Vulvar Neoplasms; DNA; RNA, Messenger; Vulva; Papillomaviridae
PubMed: 37840151
DOI: 10.1111/aogs.14689