Cancer-causing Viruses Research Articles

Structures of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus virions reveal species-specific tegument and envelope features.

Discovered in 1964, Epstein-Barr virus (EBV) is the first identified human oncogenic virus and the founding member of the gammaherpesvirus subfamily. In 1994, another cancer-causing virus was discovered in lesions of AIDS patients and later named Kaposi's sarcoma-associated herpesvirus (KSHV), the second human gammaherpesvirus. Despite the historical importance of EBV and KSHV, technical difficulties with isolating large quantities of these viruses and the pleiomorphic nature of their envelope and tegument layers have limited structural characterization of their virions. In this study, we employed the latest technologies in cryogenic electron microscopy (cryoEM) and tomography (cryoET) supplemented with an artificial intelligence-powered data processing software package to reconstruct 3D structures of the EBV and KSHV virions. We uncovered unique properties of the envelope glycoproteins and tegument layers of both EBV and KSHV. Comparison of these features with their non-tumorigenic counterparts provides insights into their relevance during infection.

KSHV ORF20 Promotes Coordinated Lytic Reactivation for Increased Infectious Particle Production.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a cancer-causing virus that establishes life-long infection. KSHV is implicated in the etiology of Kaposi's sarcoma, and a number of rare hematopoietic malignancies. The present study focuses on the KSHV open reading frame 20 (ORF20), a member of the conserved herpesvirus UL24 protein family containing five conserved homology domains and a conserved PD-(D/E)XK putative endonuclease motif, whose nuclease function has not been established to date. ORF20 encodes three co-linear protein isoforms, full length, intermediate, and short, though their differential functions are unknown. In an effort to determine the role of ORF20 during KSHV infection, we generated a recombinant ORF20-Null KSHV genome, which fails to express all three ORF20 isoforms. This genome was reconstituted in iSLK cells to establish a latent infection, which resulted in an accelerated transcription of viral mRNAs, an earlier accumulation of viral lytic proteins, an increase in the quantity of viral DNA copies, and a significant decrease in viral yield upon lytic reactivation. This was accompanied by early cell death of cells infected with the ORF20-Null virus. Functional complementation of the ORF20-Null mutant with the short ORF20 isoform rescued KSHV production, whereas its endonuclease mutant form failed to enhance lytic reactivation. Complementation with the short isoform further revealed a decrease in cell death as compared with ORF20-Null virus. Finally, expression of IL6 and CXCL8, previously shown to be affected by the hCMV UL24 homolog, was relatively low upon reactivation of cells infected with the ORF20-Null virus. These findings suggest that ORF20 protein, with its putative endonuclease motif, promotes coordinated lytic reactivation for increased infectious particle production.

The role of RNA viruses in human cancers

Many RNA viruses have been reported to be oncogenic (or carcinogenic) in a variety of animal and human cancers. The increase in the incidence and prevalence of cancer-causing viruses in human populations can be known as a key precursor to the development of various cancers. The retrovirus family and Hepatitis C virus (HCV) are also reported to cause cancer. Viral oncoproteins such as Tax of HTLV 1 interacts with cellular ubiquitination complex such as cyclindromatosis tumor suppressor, ubiquitin-specific proteases 7, 11, 15 and 20, A-20 and signal-transducing adaptor molecule binding protein-like-1 in order to improve the cellular signaling pathways. The viral oncoproteins binding to DUB, leading to proliferation of virus-infected cells and cell transformation. Proto-oncogenes (c-onc genes) are the cellular form of v-onc genes. The activation of c-onc genes leads to cell growth. C-onc genes are transformed into an oncogenic form by viral infection. C-onc genes play some roles such as protein kinases, growth factors, growth factor receptors, and DNA binding proteins. The study of transforming retroviruses and their oncogenes and the multiple mechanisms deployed by other RNA viruses to use the growth-suppressive and proapoptotic function of tumor suppressor genes has been added to our current understanding of cancer biology. Oncogenic RNA viruses are important experimental models to study molecular investigation such as cellular networks, including the discovery of oncogenes and tumor suppressors. Understanding of different strategies of RNA viruses as well as the function of their proteins helps to make more extensive plans regarding the adoption of follow-up, prevention and treatment strategies in cancer patients caused by viral origin.

Polyploid Giant Cancer Cells: A Distinctive Feature in the Transformation of Epithelial Cells by High-Risk Oncogenic HCMV Strains.

Human cytomegalovirus (HCMV) infection is common in tumor tissues across different types of cancer. While HCMV has not been recognized as a cancer-causing virus, numerous studies hint at its potential role in cancer development where its presence in various cancers corresponds with the hallmarks of cancer. Herein, we discuss and demonstrate that high-risk HCMV-DB and BL strains have the potential to trigger transformation in epithelial cells, including human mammary epithelial cells (HMECs), ovarian epithelial cells (OECs), and prostate epithelial cells (PECs), through the generation of polyploid giant cancer cells (PGCCs). A discussion is provided on how HCMV infection creates a cellular environment that promotes oncogenesis, supporting the continuous growth of CMV-transformed cells. The aforementioned transformed cells, named CTH, CTO, and CTP cells, underwent giant cell cycling with PGCC generation parallel to dedifferentiation, displaying stem-like characteristics and an epithelial-mesenchymal transition (EMT) phenotype. Furthermore, we propose that giant cell cycling through PGCCs, increased EZH2 expression, EMT, and the acquisition of malignant traits represent a deleterious response to the cellular stress induced by high-risk oncogenic HCMV strains, the latter being the origin of the transformation process in epithelial cells upon HCMV infection and leading to adenocarcinoma of poor prognosis.

Structures of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus virions reveal species-specific tegument and envelope features.

Discovered in 1964, Epstein-Barr virus (EBV) is the first identified human oncogenic virus and the founding member of the gammaherpesvirus subfamily. In 1994, another cancer-causing virus was discovered in lesions of AIDS patients and later named Kaposi's sarcoma-associated herpesvirus (KSHV), the second human gammaherpesvirus. Despite the historical importance of EBV and KSHV, technical difficulties with isolating large quantities of these viruses and the pleiomorphic nature of their envelope and tegument layers have limited structural characterization of their virions. In this study, we employed the latest technologies in cryogenic electron microscopy (cryoEM) and tomography (cryoET) supplemented with an artificial intelligence-powered data processing software package to reconstruct 3D structures of the EBV and KSHV virions. We uncovered unique properties of the envelope glycoproteins and tegument layers of both EBV and KSHV. Comparison of these features with their non-tumorigenic counterparts provides insights into their relevance during infection.

Tribute to Anthony Epstein who discovered the first human cancer-causing Epstein-Barr virus: The subject in precise on his demise

Tribute to Anthony Epstein who discovered the first human cancer-causing Epstein-Barr virus: The subject in precise on his demise

Sir Michael George Parke Stoker. 4 July 1918—13 August 2013

Michael Stoker was a renowned virologist and cell biologist. He gained his interest in research while serving as a medical officer during the Second World War in India, studying infectious diseases such as typhus. He began to study viruses in the Department of Pathology in Cambridge and in 1958 was appointed to the first established UK chair of virology and as head of the Medical Research Council Virus Unit at the University of Glasgow. He pioneered studies of cancer-causing viruses using polyomavirus of mice, and developed the baby hamster kidney cell lines still used today for vaccine production. In 1968 he moved to London as director of research at the Imperial Cancer Research Fund (ICRF) Laboratories, now part of the Cancer Research UK funded laboratories at the Francis Crick Institute. He brought many virologists to ICRF, while he himself turned to cell biology, first of mesenchymal cells and then of normal and malignant epithelial cells, particularly breast epithelium. Returning to Cambridge in 1978, he discovered scatter factor (also known as hepatocyte growth factor), a paracrine cytokine that stimulates motility and proliferation of epithelial cells. Michael had broad-ranging interests and there are few virologists in the UK who have not been influenced either by him directly or by his protégés. Among the many activities beyond the institutions where he worked, he served from 1976 to 1981 as Foreign Secretary and Vice-President of the Royal Society.

Awareness of human papillomavirus infection among Indigenous males in North America and Oceania: a Scoping Review.

Human papillomavirus (HPV) is the most commonly transmitted sexually transmitted infection. HPV infections have been on the rise among males, especially in the form of oropharyngeal cancer. Despite this, there is a gap in healthcare guidelines to increase HPV vaccine administration among males. In this study, we focus on the Indigenous population of North America and Oceania to determine existing barriers resulting in low HPV vaccination rates among the population. We surveyed peer-reviewed literature on the awareness of HPV infection among Indigenous males in North America and Oceania. Using keywords HPV plus male, men or boy, and ethnical filters such as Indigenous, Aboriginal or First Nations, we retrieved 54 articles based on titles, of which 15 were included after reading the abstracts. Reported HPV awareness was generally low in Indigenous males in North America, with no peer-reviewed data from Oceania. The lower understanding by males compared to females was largely attributable to misconceptions about HPV-related diseases, their transmission, and prevention. Lack of awareness and concern toward the risk of contracting HPV infection in Indigenous males suggests an impediment in disseminating health information about this cancer-causing virus. Culturally sensitive education, with emphasis on Indigenous males, is needed to improve this group's HPV knowledge. Researchers should also engage meaningfully with Indigenous communities by building rapport to achieve a positive change in attitude.

Co-infection of high-risk Human papillomavirus and Human T-lymphotropic virus-1 among women living with HIV on antiretroviral therapy at a tertiary hospital in Kenya

BackgroundGlobally, 15% of reported cancers are virus-associated. Cancer-causing viruses include high-risk Human papillomavirus (HR-HPV), the causative agent of cervical cancer, and Human T-lymphotropic virus type-1 (HTLV-1), the causative agent of adult T-cell leukemia (ATL). HTLV-1 infection may enhance susceptibility to acquiring HR-HPV infections due to its retrovirus properties, resulting in increased cervical abnormalities among women living with HIV (WLHIV). In Kenya, there is a paucity of data on the burden of HR-HPV/HTLV-1 co-infection among WLHIV. We determined the prevalence of HR-HPV and HTLV-1 co-infection among WLHIV on antiretroviral therapy (ART) at Kenya’s national referral hospital, Kenyatta National Hospital (KNH).MethodologyWe conducted a cross-sectional study among WLHIV on ART attending KNH’s HIV care clinic. Study nurses collected a cervical sample with a cytobrush for HPV genotyping using Gene Xpert ® assays and HPV Genotypes 14 Real-TM Quant. Peripheral blood mononuclear cells were used for HTLV-1 DNA detection. Differences in frequency distributions of characteristics between WLHIV with and without HR-HPV and HTLV-1 co-infections were assessed using the Chi-square tests.ResultsA total of 647 WLHIV enrolled in this study with a mean age of 42.8 years (SD 8.7); 93% were on ART for >1 year and 8.8% were not virally suppressed (>1000 HIV RNA copies/mL). The HTLV-1 positivity rate among WLHIV was 3.1% overall and 7.6% among those with HR-HPV. WLHIV with HR-HPV 31 had the highest proportion of HR-HPV/HTLV-1 co-infection (31.6%). In contrast, WLHIV with HR-HPV 39 had the lowest proportion of co-infection (7.1%). Participants with HR-HPV/HTLV-1 co-infections were older compared to those without the co-infections (35.2% vs. 23.3%). A higher proportion of women with HR-HPV/HTLV-1 co-infections had their sex debut before the age of 18 years (p=0.012). Women co-infected with HR-HPV/HTLV-1 were diagnosed with HIV at ≥ 35 years compared to those without infection (70.6% vs. 41.9%, p= 0.019).ConclusionWe found that HTLV-1 infection was more common among WLHIV on ART who also had HR-HPV and that co-infections were associated with the age of sexual debut and the age of HIV diagnosis.

Why Discovery of PSA was not Granted a Nobel Prize?

This essay draws attention to the prostate-specific antigen (PSA) discovery's lack of Nobel Prize acknowledgement despite its significance for prostate cancer (PCa) clinical practice. The Nobel Prize committee gives more weight to discoveries in basic research than to applications in medicine, which may account for PSA's lack of recognition. The prize has been dominated by the identification of cancer-causing viruses. Considering the subject from our -urologists- side, numerous pioneer researchers have uncovered PSA's presence and function, and its overuse in PCa screening has sparked debates about issues like overdiagnosis and overtreatment. We must concur that the factors contributing to PSA's underappreciation include the lack of a clear pioneer in its discovery and the contradictory opinions around its use. As a conclusion, PSA may have to wait for a better application before it receives recognition in the Nobel Prize.

Cancer Virus Hunters: A History of Tumor Virology by Gregory J. Morgan

‘Cancer Virus Hunters’ is an impressive work of history of medical research, deeply and extensively researched. It aims to show who and how ideas about cancer-causing viruses evolved over the twentieth century. In its approach, it pays homage to the 1926 classic ‘Microbe Hunters’ by Paul de Kruif, and shares that book’s twin goals: firstly, to explain the development of medical science by pulling back the curtain on research processes and the researchers themselves, and secondly, giving due credit for discoveries and advances. ‘Cancer Virus Hunters’ gives that approach a modern twist. It acknowledges the role of luck, serendipity and chance and the unplanned directions research can go in—this is no straightforward march-of-progress tale. And it adds an exploration of the role of wider influences on research such as wartime or institutional support, and grapples with the dark side of the issue of credit: that women made significant contributions to cancer virus research but received only a fraction of the acknowledgement for them than their male peers.

Molecular Mechanisms of Flavonoids against Tumor Gamma-Herpesviruses and Their Correlated Cancers—A Focus on EBV and KSHV Life Cycles and Carcinogenesis

Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to achieving effective therapies for viral infections and cancer. Thus, new medications with dual antiviral and anticancer actions are highly needed. Flavonoids are secondary metabolites biosynthesized by plants with diverse therapeutic effects on human health. In this review, we feature the potential role of flavonoids (flavones, protoflavones, isoflavones, flavanones, flavonols, dihydroflavonols, catechins, chalcones, anthocyanins, and other flavonoid-type compounds) in controlling gamma-herpesvirus-associated cancers by blocking EBV and KSHV infections and inhibiting the formation and growth of the correlated tumors, such as nasopharyngeal carcinoma, Burkitt's lymphoma, gastric cancer, extranodal NK/T-cell lymphoma, squamous cell carcinoma, Kaposi sarcoma, and primary effusion lymphoma. The underlying mechanisms via targeting EBV and KSHV life cycles and carcinogenesis are highlighted. Moreover, the effective concentrations or doses are emphasized.

The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi's sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) Tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate on recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer-causing viruses.

Recent advances in electrochemical biosensors for detection of oncoviruses

Oncoviruses are responsible for less than half of cancers in humans. In virus-related human oncogenesis, a multi-step process leads normal cells to transform into cancerous cells in the body. Among the various oncoviruses are human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV) and hepatitis C virus (HCV), human immunodeficiency virus (HIV), human herpesvirus (HHV-8), human lymphotropic virus-1 (HTLV-1), Merkel cell polyomavirus (MCV). The Pap smear test is critical in HPV screening, but its sensitivity is relatively low in cervical lesions, and the probability of giving false results is high. In this situation, create an alternative screening method. Therefore, the applied electroanalytical measurement techniques and electrode systems are important for detecting oncoviruses using electrochemical biosensors. Electrochemical sensor strategies such as genosensors, CRISPR-based recognition assay, aptamer-based biosensors, and immunosensors are used for the detection of oncoviruses. Major viruses causing cancer and oncovirus-related cancer types and electrochemical sensor strategies are described in the review. Studies that have been published in recent years are reported in tables for explaining details. This review considered the articles published in the last 10 years. The biosensor studies for cancer-causing viruses get gradually increased.

Proteases and HPV-Induced Carcinogenesis

Simple SummaryHuman papillomavirus (HPV) infection is a sexually transmitted disease with high prevalence worldwide. Although most HPV infections do not lead to cancer, some HPV types are correlated with the majority of cervical cancers, and with some anogenital and oropharyngeal cancers. Moreover, enzymes known as proteases play an essential role in the pathogenic process in HPV-induced carcinogenesis. This review highlights the role of proteases and recent epidemiological data regarding HPV-dependent carcinogenesis.Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival.

Cancer Screening Tests, Diagnostic Methods and Cancer Vaccines

Cancer is one of the most common causes of death in the world, observed with the uncontrolled growth of abnormal cells in any part of the body. Early diagnosis with screening programs in individuals with no suspicion of cancer or with the precancerous is important in terms of increasing the quality of life of the patient and taking precautions against the risks that may occur in the future. Early diagnosis of cancer using various diagnostic methods increases the success of treatment. Immunotherapy methods that strengthen the immune system and initiate a new era in anticancer therapy are used in the treatment. This method involves changing a patient's immune cells using biotechnology. Cancer vaccines are one of the therapeutic methods that are frequently studied recently and can develop a clinical response that can completely cure the disease. The vaccine creates an antitumor immune response in individuals with cancer, prevents cancer-causing viruses and infections, and reduces the risk of cancer development in some high-risk individuals.

Global CpG DNA Methylation Footprint in Kaposi's Sarcoma.

Kaposi’s sarcoma-associated herpesvirus (KSHV), also familiar as human herpesvirus 8 (HHV-8), is one of the well-known human cancer-causing viruses. KSHV was originally discovered by its association with Kaposi’s sarcoma (KS), a common AIDS-related neoplasia. Additionally, KSHV is associated with two B-lymphocyte disorders; primary effusion lymphoma (PEL) and Multicentric Castlemans Disease (MCD). DNA methylation is an epigenetic modification that is essential for a properly functioning human genome through its roles in chromatin structure maintenance, chromosome stability and transcription regulation. Genomic studies show that expressed promoters tend to be un-methylated whereas methylated promoters tend to be inactive. We have previously revealed the global methylation footprint in PEL cells and found that many cellular gene promoters become differentially methylated and hence differentially expressed in KSHV chronically infected PEL cell lines. Here we present the cellular CpG DNA methylation footprint in KS, the most common malignancy associated with KSHV. We performed MethylationEPIC BeadChip to compare the global methylation status in normal skin compared to KS biopsies, and revealed dramatic global methylation alterations occurring in KS. Many of these changes were attributed to hyper-methylation of promoters and enhancers that regulate genes associated with abnormal skin morphology, a well-known hallmark of KS development. We observed six-fold increase in hypo-methylated CpGs between early stage of KS (plaque) and the more progressed stage (nodule). These observations suggest that hyper-methylation takes place early in KS while hypo-methylation is a later process that is more significant in nodule. Our findings add another layer to the understanding of the relationship between epigenetic changes caused by KSHV infection and tumorigenesis.

Combating Human Viral Diseases: Will Plant-Based Vaccines Be the Answer?

Molecular pharming or the technology of application of plants and plant cell culture to manufacture high-value recombinant proteins has progressed a long way over the last three decades. Whether generated in transgenic plants by stable expression or in plant virus-based transient expression systems, biopharmaceuticals have been produced to combat several human viral diseases that have impacted the world in pandemic proportions. Plants have been variously employed in expressing a host of viral antigens as well as monoclonal antibodies. Many of these biopharmaceuticals have shown great promise in animal models and several of them have performed successfully in clinical trials. The current review elaborates the strategies and successes achieved in generating plant-derived vaccines to target several virus-induced health concerns including highly communicable infectious viral diseases. Importantly, plant-made biopharmaceuticals against hepatitis B virus (HBV), hepatitis C virus (HCV), the cancer-causing virus human papillomavirus (HPV), human immunodeficiency virus (HIV), influenza virus, zika virus, and the emerging respiratory virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been discussed. The use of plant virus-derived nanoparticles (VNPs) and virus-like particles (VLPs) in generating plant-based vaccines are extensively addressed. The review closes with a critical look at the caveats of plant-based molecular pharming and future prospects towards further advancements in this technology. The use of biopharmed viral vaccines in human medicine and as part of emergency response vaccines and therapeutics in humans looks promising for the near future.

RNA-guided gene editing of the murine gammaherpesvirus 68 genome reduces infectious virus production.

Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV) are cancer-causing viruses that establish lifelong infections in humans. Gene editing using the Cas9-guideRNA (gRNA) CRISPR system has been applied to decrease the latent load of EBV in human Burkitt lymphoma cells. Validating the efficacy of Cas9-gRNA system in eradicating infection in vivo without off-target effects to the host genome will require animal model systems. To this end, we evaluated a series of gRNAs against individual genes and functional genomic elements of murine gammaherpesvirus 68 (MHV68) that are both conserved with KSHV and important for the establishment of latency or reactivation from latency in the host. gRNA sequences against ORF50, ORF72 and ORF73 led to insertion, deletion and substitution mutations in these target regions of the genome in cell culture. Murine NIH3T3 fibroblast cells that stably express Cas9 and gRNAs to ORF50 were most resistant to replication upon de novo infection. Latent murine A20 B cell lines that stably express Cas9 and gRNAs against MHV68 were reduced in their reactivation by approximately 50%, regardless of the viral gene target. Lastly, co-transfection of HEK293T cells with the vector expressing the Cas9-MHV68 gRNA components along with the viral genome provided a rapid read-out of gene editing and biological impact. Combinatorial, multiplex MHV68 gRNA transfections in HEK293T cells led to near complete ablation of infectious particle production. Our findings indicate that Cas9-gRNA editing of the murine gammaherpesvirus genome has a deleterious impact on productive replication in three independent infection systems.

Current Updates on Cancer-Causing Types of Human Papillomaviruses (HPVs) in East, Southeast, and South Asia.

Human papillomavirus (HPV) infection remains one of the most prominent cancer-causing DNA viruses, contributing to approximately 5% of human cancers. While association between HPV and cervical cancers has been well-established, evidence on the attribution of head and neck cancers (HNC) to HPV have been increasing in recent years. Among the cancer-causing HPV genotypes, HPV16 and 18 remain the major contributors to cancers across the globe. Nonetheless, the distribution of HPV genotypes in ethnically, geographically, and socio-economically diverse East, Southeast, and South Asia may differ from other parts of the world. In this review, we garner and provide updated insight into various aspects of HPV reported in recent years (2015-2021) in these regions. We included: (i) the HPV genotypes detected in normal cancers of the uterine cervix and head and neck, as well as the distribution of the HPV genotypes by geography and age groups; (ii) the laboratory diagnostic methods and treatment regimens used within these regions; and (iii) the oncogenic properties of HPV prototypes and their variants contributing to carcinogenesis. More importantly, we also unveil the similarities and discrepancies between these aspects, the areas lacking study, and the challenges faced in HPV studies.