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Recent Results in Cancer Research.... 2021Human papillomavirus (HPV) is the most common sexually transmitted infection, currently affecting close to 80 million Americans. Importantly, HPV infection is recognized...
Human papillomavirus (HPV) is the most common sexually transmitted infection, currently affecting close to 80 million Americans. Importantly, HPV infection is recognized as the etiologic factor for numerous cancers, including cervical, vulval, vaginal, penile, anal, and a subset of oropharyngeal cancers. The prevalence of HPV infection and its associated diseases are a significant problem, affecting millions of individuals worldwide. Likewise, the incidence of HPV infection poses a significant burden on individuals and the broader healthcare system. Between 2011 and 2015, there were an estimated 42,700 new cases of HPV-associated cancers each year in the United States alone. Similarly, the global burden of HPV is high, with around 630,000 new cases of HPV-associated cancer occurring each year. In the last decade, a total of three preventive major capsid protein (L1) virus-like particle-based HPV vaccines have been licensed and brought to market as a means to prevent the spread of HPV infection. These prophylactic vaccines have been demonstrated to be safe and efficacious in preventing HPV infection. The most recent iteration of the preventive HPV vaccine, a nanovalent, L1-VLP vaccine, protects against a total of nine HPV types (seven high-risk and two low-risk HPV types), including the high-risk types HPV16 and HPV18, which are responsible for causing the majority of HPV-associated cancers. Although current prophylactic HPV vaccines have demonstrated huge success in preventing infection, existing barriers to vaccine acquisition have limited their widespread use, especially in low- and middle-income countries, where the burden of HPV-associated diseases is highest. Prophylactic vaccines are unable to provide protection to individuals with existing HPV infections or HPV-associated diseases. Instead, therapeutic HPV vaccines capable of generating T cell-mediated immunity against HPV infection and associated diseases are needed to ameliorate the burden of disease in individuals with existing HPV infection. To generate a cell-mediated immune response against HPV, most therapeutic vaccines target HPV oncoproteins E6 and E7. Several types of therapeutic HPV vaccine candidates have been developed including live-vector, protein, peptide, dendritic cell, and DNA-based vaccines. This chapter will review the commercially available prophylactic HPV vaccines and discuss the recent progress in the development of therapeutic HPV vaccines.
Topics: Alphapapillomavirus; Female; Humans; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccination
PubMed: 33200366
DOI: 10.1007/978-3-030-57362-1_8 -
Frontiers in Bioscience (Elite Edition) Jan 2018Human papillomavirus (HPV) infection is linked to development of cancer of cervix, vagina, vulva, penis, ano-genital and non-genital oro-pharyngeal sites. HPV being a... (Review)
Review
Human papillomavirus (HPV) infection is linked to development of cancer of cervix, vagina, vulva, penis, ano-genital and non-genital oro-pharyngeal sites. HPV being a sexually transmitted virus infects both genders equally but with higher chances of pathological outcome in women. In the absence of organized screening programs, women report HPV-infected lesions at relatively advanced stages where they are subjected to standard treatments that are not HPV-specific. HPV infection-driven lesions usually take 10-20 years for malignant progression and are preceded by well-characterized pre-cancer stages. Despite availability of window for pharmacological intervention, therapeutic that could eradicate HPV from infected lesions is currently lacking. A variety of experimental approaches have been made to address this lacuna and there has been significant progress in a number of lead molecules which are in different stages of clinical and pre-clinical development. Present review provides a brief overview of the magnitude of the problem and current status of research on promising lead molecules, formulations and therapeutic strategies that showed potential to translate to clinically-viable HPV therapeutics to counteract this reproductive health challenge.
Topics: Alphapapillomavirus; Female; Gene Silencing; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Male; Papillomavirus Infections; Papillomavirus Vaccines; RNA Interference; RNA, Viral; Tumor Virus Infections
PubMed: 28930604
DOI: 10.2741/e808 -
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 -
Archives of Pathology & Laboratory... Jun 2018- The prevalence of human papillomavirus (HPV) infection varies worldwide. The high-risk viruses are usually associated with cancers of the cervix, vagina, and vulva in... (Review)
Review
CONTEXT
- The prevalence of human papillomavirus (HPV) infection varies worldwide. The high-risk viruses are usually associated with cancers of the cervix, vagina, and vulva in women, cancer of the penis in men, and cancers of the anus, tonsils, oropharynx, and base of the tongue in both sexes.
OBJECTIVES
- To review literature about the challenges and burden associated with HPV infection in low-resource (ie, developing) countries, focusing on sub-Saharan Africa. To review the prevention, incidence, prevalence, morbidity, and mortality of HPV infections in sub-Saharan Africa. To review the therapy and management of HPV infections in low-resource countries in comparison to developed countries.
DATA SOURCES
- Peer-reviewed literature and experience of some of the authors.
CONCLUSIONS
- Sub-Saharan Africa has high HPV infection prevalence rates, with predominance of high-risk subtypes 16, 18, and 45. The difficulty of access to health care has led to higher morbidity and mortality related to HPV-related cancers. Improvement in screening programs will help in monitoring the spread of HPV infections. Survival studies can be more informative if reliable cancer registries are improved. HPV vaccination is not yet widely available and this may be the key to curtailing the spread of HPV infections in resource-poor countries.
Topics: Africa South of the Sahara; Developing Countries; Female; Humans; Incidence; Male; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 29848027
DOI: 10.5858/arpa.2017-0565-RA -
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 -
Journal of Clinical Medicine Feb 2022Human papillomavirus (HPV) infection drives tumorigenesis in almost all cervical cancers and a fraction of vulvar and penile cancers. Due to increasing incidence and low... (Review)
Review
Human papillomavirus (HPV) infection drives tumorigenesis in almost all cervical cancers and a fraction of vulvar and penile cancers. Due to increasing incidence and low vaccination rates, many will still have to face HPV-related morbidity and mortality in the upcoming years. Current treatment options (i.e., surgery and/or chemoradiation) for urogenital (pre-)malignancies can have profound psychosocial and psychosexual effects on patients. Moreover, in the setting of advanced disease, responses to current therapies remain poor and nondurable, highlighting the unmet need for novel therapies that prevent recurrent disease and improve clinical outcome. Immunotherapy can be a useful addition to the current therapeutic strategies in various settings of disease, offering relatively fewer adverse effects and potential improvement in survival. This review discusses immune evasion mechanisms accompanying HPV infection and HPV-related tumorigenesis and summarizes current immunotherapeutic approaches for the treatment of HPV-related (pre-)malignant lesions of the uterine cervix, vulva, and penis.
PubMed: 35207374
DOI: 10.3390/jcm11041101 -
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 -
American Journal of Obstetrics and... Sep 2015The aim of this study was to systematically review the findings of publications addressing the epidemiology of anal human papillomavirus (HPV) infection, anal... (Review)
Review
The aim of this study was to systematically review the findings of publications addressing the epidemiology of anal human papillomavirus (HPV) infection, anal intraepithelial neoplasia, and anal cancer in women. We conducted a systematic review among publications published from Jan. 1, 1997, to Sept. 30, 2013, to limit to publications from the combined antiretroviral therapy era. Three searches were performed of the National Library of Medicine PubMed database using the following search terms: women and anal HPV, women anal intraepithelial neoplasia, and women and anal cancer. Publications were included in the review if they addressed any of the following outcomes: (1) prevalence, incidence, or clearance of anal HPV infection, (2) prevalence of anal cytological or histological neoplastic abnormalities, or (3) incidence or risk of anal cancer. Thirty-seven publications addressing anal HPV infection and anal cytology remained after applying selection criteria, and 23 anal cancer publications met the selection criteria. Among HIV-positive women, the prevalence of high-risk (HR)-HPV in the anus was 16-85%. Among HIV-negative women, the prevalence of anal HR-HPV infection ranged from 4% to 86%. The prevalence of anal HR-HPV in HIV-negative women with HPV-related pathology of the vulva, vagina, and cervix compared with women with no known HPV-related pathology, varied from 23% to 86% and from 5% to 22%, respectively. Histological anal high-grade squamous intraepithelial lesions (anal intraepithelial neoplasia 2 or greater) was found in 3-26% of the women living with HIV, 0-9% among women with lower genital tract pathology, and 0-3% for women who are HIV negative without known lower genital tract pathology. The incidence of anal cancer among HIV-infected women ranged from 3.9 to 30 per 100,000. Among women with a history of cervical cancer or cervical intraepithelial neoplasia 3, the incidence rates of anal cancer ranged from 0.8 to 63.8 per 100,000 person-years, and in the general population, the incidence rates ranged from 0.55 to 2.4 per 100,000 person-years. This review provides evidence that anal HPV infection and dysplasia are common in women, especially in those who are HIV positive or have a history of HPV-related lower genital tract pathology. The incidence of anal cancer continues to grow in all women, especially those living with HIV, despite the widespread use of combined antiretroviral therapy.
Topics: Antiretroviral Therapy, Highly Active; Anus Diseases; Anus Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Coinfection; Female; HIV Infections; Humans; Incidence; Papillomavirus Infections; Prevalence; Proctitis
PubMed: 25797230
DOI: 10.1016/j.ajog.2015.03.034 -
Microorganisms May 2022Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a... (Review)
Review
Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease.
PubMed: 35630489
DOI: 10.3390/microorganisms10051047 -
Journal of Clinical Virology : the... Jul 2023Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA; cHPV DNA) in blood referred to as "liquid biopsy" may support the early diagnosis and monitoring of affected individuals.
METHODS
A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
RESULTS
A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
CONCLUSION
ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Anus Neoplasms; DNA
PubMed: 37163963
DOI: 10.1016/j.jcv.2023.105469