Human Papillomavirus Variants Research Articles

Molecular epidemiology of human papillomavirus variants in cervical cancer in India

Background & objectives Cervical cancer (CC) has been documented as the fourth most common cancer worldwide. Persistent infections with high-risk human papillomavirus (hr-HPV) have been suggested in the development of CC. Although prophylactic vaccines are available for the prevention of prevalent hr-HPV types, intra-type variations exist within a particular HPV type that has varying oncogenic potential as well as the mechanism of pathogenicity and varying neutralization by antibodies. Therefore, we carried out a systematic review to determine the distribution of HPV intra-typic variations in different geographical locations of India and their reported implications. Methods Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed to retrieve relevant articles from the standard databases using appropriate keywords. Consequently, 17 articles were included in the current review after screening based on inclusion and exclusion criteria. Results The majority of articles included in this review reported variations within the HPV16 E6 gene, followed by the L1 and E7 genes. Analysis of available data indicated the differential regional distribution of some variations. These variations have also been reported to impact the biological functions of various viral proteins. Interpretation & conclusions The distribution of lineages varied with the different genomic regions sequenced. Additionally, there were certain unique and common variations in the HPV genome with respect to geographical regions. Hence, we suggest the identification of region-specific variations for the development of diagnostic and prognostic interventions.

Prevalence and distribution of human papillomavirus genotypes in women with abnormal cervical cytology in Ethiopia: a systematic review and meta-analysis.

Cervical cancer is the 4th most common cancer in women globally. Determining the prevalence of the high-risk human papillomavirus (HR-HPV) and low-risk (LR-HPV) genotypes and the distribution in abnormal cervical cytology will be essential in a future population-based cervical cancer prevention program. Primary studies with women with abnormal cervical cytology were systematically searched for in Medline, CINHAL, Google Scholar, African Journal Online, and the University of Antwerp repository from 19-30 May 2023. A weighted inverse-variance random effects model was used. Variations across the studies were checked using a forest plot, I2 statistics, and Egger's test. Group analysis was performed for evidence of heterogeneity. The pooled prevalence of human papillomavirus (HPV) genotypes with abnormal cervical cytology of a precancerous cervical lesion was 38.74% (95% CI: 27.56-49.93). The leading pooled prevalence estimates by subgroup analysis were 18% (95% CI: 13-26), 14% (95% CI: 111-16), and 66% (51-79) for women with retroviral infection (RVI), DNA genotyping with amplification, and central parts of Ethiopia respectively. There were 25 HPV variants identified by genotyping techniques with the five most prevalent HPV genotypes being HPV-16 and HPV-18 coexisting at 54%; HPV-16 alone at 29%; HPV-51 at 16%; HPV-52 at 13%; and HPV-31 and HPV-33 each contributing approximately 12%. The pooled prevalence of HPV genotypes was higher than in other countries. HPV-51, HPV-52, HPV-31, and HPV-33 are the most prevalent genotypes. Hence, the nonavalent vaccine type would be the one that includes all the most prevalent HPV genotypes, but HPV-51in Ethiopia. Additional data on similar DNA test techniques for comparisons with precancerous lesions and invasive cancer are needed. Cervical cancer prevention and control programs in Ethiopia should be aligned with the most prevalent genotypes. https://www.crd.york.ac.uk/prospero/, identifier CRD42023428955.

Characterization of High-Risk-Other Human Papillomavirus Genotypes in Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, and Cervical Cancer.

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for HPV genotype determination by Roche Linear Array (Roche Diagnostics, North America). Then we randomly selected 76 cervical biopsy samples of HGSIL or cervical cancer with high-risk-other HPV or HPV unknown status from 2016 to 2022 for HPV genotype determination by next-generation sequencing. Results are reported as counts and frequencies. Results: In the 50 high-risk-other HPV Pap test samples, 21 genotypes of HPV were noted; the most common were 53 (n=6), 51 (n=6), and 59 (n=5). In the samples with HGSIL or cervical cancer, 16 HPV genotypes were detected; the most common were 16 (n=26), 58 (n=12), and 33 (n=8). Among the patients with HGSIL or cervical cancer, the 9-valent HPV vaccine provided coverage for all the HPV variants found in 88% of patients, partial coverage in 8% of patients, and no coverage in 4% of patients. Conclusion: The 3 most common HPV genotypes seen in our high-risk-other HPV Pap test samples are not covered by the 9-valent HPV vaccine. For the HGSIL and cancer samples, 88% of the samples had full HPV genotype coverage with the 9-valent HPV vaccine. This study highlights a presence of HPV that will not be protected by vaccination in a high-risk population.

The effect of phosphorylation efficiency on the oncogenic properties of the protein E7 from high-risk HPV

The Human papillomavirus (HPV) causes tumors in part by hijacking the host cell cycle and forcing uncontrolled cellular division. While there are >200 genotypes of HPV, 15 are classified as high-risk and have been shown to transform infected cells and contribute to tumor formation. The remaining low-risk genotypes are not considered oncogenic and result in benign skin lesions. In high-risk HPV, the oncoprotein E7 contributes to the dysregulation of cell cycle regulatory mechanisms. High-risk E7 is phosphorylated in cells at two conserved serine residues by Casein Kinase 2 (CK2) and this phosphorylation event increases binding affinity for cellular proteins such as the tumor suppressor retinoblastoma (pRb). While low-risk E7 possesses similar serine residues, it is phosphorylated to a lesser degree in cells and has decreased binding capabilities. When E7 binding affinity is decreased, it is less able to facilitate complex interactions between proteins and therefore has less capability to dysregulate the cell cycle. By comparing E7 protein sequences from both low- and high-risk HPV variants and using site-directed mutagenesis combined with NMR spectroscopy and cell-based assays, we demonstrate that the presence of two key nonpolar valine residues within the CK2 recognition sequence, present in low-risk E7, reduces serine phosphorylation efficiency relative to high-risk E7. This results in significant loss of the ability of E7 to degrade the retinoblastoma tumor suppressor protein, thus also reducing the ability of E7 to increase cellular proliferation and reduce senescence. This provides additional insight into the differential E7-mediated outcomes when cells are infected with high-risk verses low-risk HPV. Understanding these oncogenic differences may be important to developing targeted treatment options for HPV-induced cancers.

Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review

ABSTRACT To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Cervical Cancer Treatment Update: A Society of Gynecologic Oncology Clinical Practice Statement

ABSTRACT Despite increased screening and human papillomavirus (HPV) vaccination in high-income countries, cervical cancer represents the fourth most diagnosed cancer in women worldwide and the second highest cause of cancer mortality among women in low- and middle-income countries. This clinical practice statement describes therapies for cervical cancer by treatment setting, as well as quality of life, financial toxicity, and disparities associated with the disease. Persistent HPV infection, particularly types 16 and 18, are the main factor in the development of cervical cancer. High-risk HPV variants integrate HPV DNA into the host genome to upregulate two viral oncoproteins, E6 and E7, which in turn inhibit the tumor suppressor proteins p53 and Rb. Certain driver mutations including PIK3CA, KRAS, and EGFR are frequently seen in cervical cancer, however further research is needed to identify an actionable biomarker based on targetable oncogenic alterations. Locally advanced cervical cancer is defined as clinically visible tumor exceeding 4 cm or invading beyond the cervix, extending to the pelvic sidewalls, vagina, bladder, rectum, or involving pelvic and/or paraaortic lymph nodes. Standard treatment for locally advanced cervical cancer is external beam radiation therapy and concurrent weekly cisplatin. Standard treatment for advanced, recurrent, or metastatic cervical cancer is cisplatin, paclitaxel, and bevacizumab (possibly adding pembrolizumab). Several studies have shown that checkpoint inhibitors, when combined or sequenced with chemoradiation, may provide survival benefit in both locally advanced and recurrent/metastatic cervical cancer. Given these findings, immunotherapy should be incorporated in treatment of advanced or recurrent disease. Negative effects on quality of life (QOL) in patients with cervical cancer often begin in people who receive negative Papanicolaou test results or positive HPV DNA tests. Negative body image, self-esteem, and relationships with partners contribute to an overall decrease in QoL. Surgical, radiation-induced, and chemotherapy-induced treatment effects further impact survivors’ physical health, body-image, and sexual function. Economic burdens of cancer diagnosis and treatment may disproportionally affect cervical cancer patients due to the intensity of curative treatment, decreases in QoL and functional status, and unique population including younger patients, those with poor access to health care at baseline, and those who identify as racial or ethnic minorities.

Unravelling the Impact of Human Papillomavirus (HPV): A Comprehensive Exploration of its Role in Cancer Progression and Global Health Challenges

HPV represents a large group of double stranded DNA viruses that are highly involved with different types of human cancers. This synopsis describes the complexities surrounding HPV virology, classifications, and genomic variation, especially focusing on high-risk strains such as HPV16 and HPV18, the main causative factors for cervical cancers. The International Committee on Taxonomy of Viruses specifies more than 200 HPV types each associated with a respective disease and indicated in Table 1. HPV spread is mostly due to direct skin-to-skin contact between individuals’ sex organs causing infections on the mucous membrane and keratinized epithelial cells. Although majority of the infections are asymptomatic, some chronic HRHPV infections may progress into cancers because of oncoproteins E6 and E7. The high-risk variants of HPV lead to cervical, anal, and oropharyngeal cancers whereas the low-risk types cause harmless genital warts. While integrating HPV DNA into the host genome, orchestrated by oncoproteins E6 and E7 disrupts the cell regulatory mechanism; this leads to abnormal control over cell multiplication–one of the major elements of the process that develops to HPV induced cancer. A classic case is cervical cancer that has been extensively investigated as one of the highly documented HPV associated malignancies. Pap smears and HPV DNA tests are among the screening means that lower the incidents and deaths associated with cervical cancers. HPV-associated cancers of the head and neck, anus, penis, vulva, and vagina all show a characteristic profile in terms of the pathogen aetiology and risks involved. HPV-related head and neck cancers affect non-smokers and show good response to standard therapies. HPV poses increased anal cancer risk for immunocompromised individuals highlighting the complexity of interdependence of immunity and cancer development. Penile cancer results from poor hygiene and non-circumcision. Vulvar and virginal cancer mostly affects women, and the risk factors involve HPV infection and smoking. Therefore, various types of multidisciplinary approach that may include surgeries, radiotherapy, and chemotherapy are necessary to ensure proper treatment. Certain cancers are strongly associated with some high-risk HPV genotypes, such as HPV-16 and HPV-18; thus, vaccination is important. HPV infection outcomes are determined by the immune response as well as clearance of HPV infection. Screening and immunological understanding for early detection of HPV related health risks is fundamental. However, this encompassing review highlights the multi-dimensional impact of HPV encompassing virology of HPV, cancer specific presentation of HPV and control including prevention of HPV infection, screening, and research on cancer attributable by HPV and strategies towards mitigation of this global health problem.

Screening of High and Low-risk Human Papillomavirus Variants in Cervical Cancer Patients by Polymerase Chain Reaction: A Cross-sectional Study

Introduction: Cervical cancer is the second most common gynaecological malignancy worldwide. Persistent Human Papillomavirus (HPV) infection is the principal risk factor leading to cervical carcinogenesis and causes a large number of casualties. Aim: To estimate the risk factors and symptoms related to cervical carcinoma and to check for mono-infection or co-infections of low-risk and high-risk HPVs in Northern Indian females. Materials and Methods: This cross-sectional study was conducted from January 2019 to January 2021 on 110 confirmed cervical cancer tissue samples collected from the Department of Obstetrics and Gynaecology at Pandit BD Sharma University of Health Sciences, Rohtak, Haryana, India. Information about risk factors and symptoms was collected using a semistructured proforma. Detection of HPV infection and HPV genotyping (16, 18, 33, 58, 6, and 11) was done by using type-specific Polymerase Chain Reaction (PCR). Fisher’s exact test was applied to determine the association of high- risk HPV infection with other risk factors using GraphPad Prism Version 6 (La Jolla, California, USA). A p-value of ≤0.05 was considered significant. Results: Of all the studied cases, 68 (62%) were above 55 years old, 67 (61%) were in a postmenopausal state, and 86 (78%) were from a rural background. Irregular menstruation was observed in 99 (90%) cases, bleeding after menopause in 59 (54%) cases, and early age at first intercourse in 57 (52%) cases were the most common symptoms. HPV infection was found in all cases of cervical carcinoma. The incidence of high- risk-HPV16 (84%) and HPV18 (73%) was the most prominent, while the incidence of low-risk-HPV6 (7.2%) and HPV11 (6%) was the lowest. Co-infection of HPV16/18 was the Highest in 60 (54.5%) cases, followed by HPV16/33 in 13 (11.8%) cases. Multi-infection of HPV types 16/18/33 was found in 10 (9.1%) cases, and multi-infection of HPV types 16/18/33/6/11, except HPV58, was found in one patient. Conclusion: Higher age, postmenopausal status, early age at intercourse, and poor menstrual hygiene were significantly associated with high-risk HPV co-infection. Educating women about the risk factors and symptoms of cervical cancer and screening for high-risk HPVs in rural women are required to reduce the prevalence of cervical cancer in Northern India.

Evaluation of anticancer activity of Gmelina asiatica leaves, in-vitro and in-silico studies

Cervical cancer poses a major threat to women’s health worldwide, constituting the fourth most prevalent cancer among the female population. High-risk variants of human papillomavirus (HPV) with its oncogenic proteins are a necessary cause of cervical cancer. Due to the resistance of cancer cells to the current treatment, there is a need for new medicines with new strategies to treat cervical cancer. Gmelina asiatica Linn. is a medicinal plant with various traditional uses and biological activities. Its anticancer potential against breast cancer and lymphoma has been demonstrated in the literature. In view of this, our study aims to investigate the anticancer activity of Gmelina asiatica leaves against cervical cancer. Various extracts of Gmelina asiatica leaves were prepared by soxhletation and maceration methods. The cytotoxic activity of the extracts was evaluated through in-vitro studies against SiHa cell line using MTT assay and fluorescence imaging. The most potent extract (GAME) phytochemical profile was analysed by UHPLC-HRMS. Further, in-silico studies were performed on its phytoconstituents against E6 oncoprotein, and the DFT studies were conducted on the active component to assess the physicochemical properties. In-vitro studies revealed that methanolic extract (GAME) showed the highest inhibition on the SiHa cell line compared to the other extracts and the control (p < 0.0001). In-silico studies indicated high affinity with stable interaction of the compound 5 (JC5ABDR) at E6 binding sites. This study revealed the importance of Gmelina asiatica plant as a potential source of anticancer molecules with a specific mode of action against cervical cancer. Communicated by Ramaswamy H. Sarma

Impact of HPV-16 Lineages Infection in Response to Radio-Chemotherapy in Cervical Cancer.

HPV is strongly related to cervical cancer. HPV lineages can contribute to a response to cervical cancer therapy. The aim of this research was to estimate the frequency of human papillomavirus (HPV)-16 lineages in specimens of cervical cancer, relate the pathological factors in these variants, and assess their response to treatment with radical chemoradiotherapy. Samples of cervical cancer were collected from women who were referred to a reference cancer hospital to test the presence of human papillomavirus-type DNA. The standard protocol of this service consisted of cisplatin-based chemotherapy of 40 mg/m2, plus conventional pelvic irradiation in doses of 45-50.4 Gy and high dose-rate brachytherapy of 28-30 Gy to Point A. The response to chemotherapy was evaluated after three months in patients with the HPV-16 lineage. HPV DNA was detected in 104 (88.1%) of the 118 patients. HPV-16 was present in 63 patients (53%). Lineages of HPV-16 were identified in 57 patients and comprised 33 instances of (57.8%) lineage A, 2 instances of lineage B (3.5%), 2 instances of lineage C (3.5%), and 20 instances of (35.0%) lineage D. The median age of the patients was 48.4 years (range 25-85 years). Squamous cell carcinoma was detected 48 times (84.2%). Adenocarcinoma was more likely to occur in lineage D, as three of the four cases occurred in this lineage. A total of 11 patients with the HPV-16 variant were treated with chemoradiotherapy. After three months, it was observed that nine of the eleven patients (81.8%) achieved a complete response, five with the lineage A type, two with the lineage C type, and two with the lineage D type. The two cases of partial response and disease progression, one of each, occurred in lineage A. In addition to the small number of patients and HPV variants, we noticed a better response in patients with the HPV-16 lineage A. Increasing the sample size could be helpful to better assess the impact of HPV variants on cervical cancer treatment.

Diversity of cervicovaginal human papillomavirus (HPV) genotypes and naturally occurring E6/E7 DNA polymorphisms of HPV-16 in Ghana

Human papillomavirus (HPV) E6 and E7 oncogene expression is essential for cervical carcinogenesis. Evidence exists that E6/E7 variants may have different transforming activities while the risk of HPV-16 variants (A/D) differs by race/ethnicity. We determined the type-specific diversity of HPV infection in women with high grade cervical disease or cervical cancer in Ghana and investigated naturally occurring E6/E7 DNA variants in this population. HPV genotyping was carried out on 207 cervical swab samples collected from women referred to a gynaecology clinic at two teaching hospitals in Ghana. HPV-16, HPV-18 and HPV-45 were detected in 41.9%, 23.3% and 16.3% of cases respectively. HPV-16 E6/E7 DNA sequencing was performed in 36 samples. Thirty samples contained E6/E7 variants of the HPV-16-B/C lineage. 21/36 samples were of the HPV-16C1 sublineage variant and all contained the E7 A647G(N29S) single nucleotide polymorphism (SNP). This study reveals the diversity of E6/E7 DNA and the dominance of HPV16 B/C variants in cervicovaginal HPV infection in Ghana. Type-specific HPV diversity analysis indicates that most Ghanaian cervical disease cases are vaccine preventable. The study provides an important baseline from which for the impact of vaccine and antivirals on clinically relevant HPV infection and associated disease can be measured.

Excurve and Emit Lobular Endocervical Glandular Hyperplasia

Lobular endocervical glandular hyperplasia of uterine cervix is a benign, exceptional lesion with a characteristic proliferation of miniature, spherical glands accompanied by gastric type differentiation. The discrete lobules incriminate upper endocervical canal of predominantly premenopausal women. Lobular endocervical glandular hyperplasia and gastric subtypes of cervical glandular lesions appear non concurrent to persistent infection with high risk variants of human papilloma virus (HPV). Cytological examination depicts mono-layered sheets of tall, columnar, mucinous cells demonstrating smooth nuclear outline with absent cellular or nuclear atypia or mitotic figures. Papanicolaou stained smears exemplify extracellular or intracellular, golden yellow mucin, indicative of gastric subtype of cellular differentiation. The well-defined lobular or acinar lesion is comprised of a centric crypt with circumscribing glandular articulations and miniature, spherical cysts which configure a floret-like pattern. Centric and peripheral glands are layered with columnar epithelial cells pervaded with pale, eosinophilic cytoplasm, bland, miniature, basal nuclei with mild nuclear atypia. Atypical cytological and architectural features may progress into the malignant ‘atypical lobular endocervical glandular hyperplasia’, currently contemplated as a category of gastric type adenocarcinoma in situ (GAIS). The lesion is immune reactive to pyloric gland mucin (HIK1083), MUC6, PAX2 or chromogranin A. Lobular endocervical glandular hyperplasia of uterine cervix requires segregation from neoplasms such as human papilloma virus (HPV) independent endocervical adenocarcinoma, gastric type, pyloric type metaplasia, gastric type adenocarcinoma in situ, type A tunnel clusters, micro glandular hyperplasia and mesonephric remnants or mesonephric hyperplasia of uterine cervix. Lesions detected upon surgical tissue sampling, cervical loop electrosurgical excision procedure (LEEP) or conisation may be optimally managed with total abdominal hysterectomy

Attitude and practice on Human Papillomavirus, Human Papillomavirus Vaccine and associated factors among population in the Republic of Kosova

Аpproximately 50–80% of sexually active women are exposed to at least one HPV variant during their lifetime. Based on the 2015 annual report of the National Institute of Public Health of Kosova, 68 new cases of cervical cancer were detected. The aim of the study was to investigate the attitude and practice regarding Human Papillomavirus (HPV) infections and the Human Papillomavirus vaccine in the population of the Republic of Kosova. Material and methods: A cross-sectional survey was conducted to assess the knowledge concerning HPV infections among the population aged 18 to 35+ years. The study was conducted during the period of time June 2021 –to August 2021. The sample included 500 participants. The questionnaire was anonymous, and participants were free to end their participation any time, without completing the questionnaire. Results: Regarding the claim "The HPV vaccine is safe", more than half of the respondents, respectively58.6% declare that they do not know, 33.4% of the respondents agree, 6.0% gave an incorrect answer / disagree, and 2.0% did not answer. The percentage difference between the unknown and correct answers is statistically significant for p&lt;0.05. Conclusion: This study found out that the attitude towards the HPV vaccine among people of the Republic of Kosova is low to moderate. HPV vaccines should be included in the national immunization programs, since there is not still established national vaccination program for HPV vaccination.

Cervical human papillomavirus genotypes in a high HIV setting: A scoping review of a decade of human papillomavirus epidemiological research in Botswana.

Cervical cancer burden is still high in low- and middle-income countries, including Botswana. Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Accurate knowledge of HPV diversity associated to cervical cancer in sub-Saharan Africa may provide accurate understanding of the natural history of HPV infection in these contexts. The goal of this review was to consolidate existing evidence on cervical HPV infection and to conduct a pooled analysis of data from all eligible Botswana studies. After a successful review of twelve studies on cervical HPV genotypes that met the inclusion criteria, HPV-16 genotype was the most frequently discovered in women with pre-cancerous and cancer lesions, followed by HPV-18. HPV-16 in HIV-positive women with precancerous lesions to cancer is between 45% and 47.7%, and between 4.5% and 26.1% for HPV-18. With reference to other HPV genotypes, the proportion of HPV-35 and HPV-58 (13-16%) seems relatively consistent among the studies, however HPV-58 appears to be more common in HIV-positive subjects compared to HIV-negative women. Indeed, HPV-45 seems to be frequently detected in women with cervical cancer compared to women with precancerous lesions. Regarding the low-risk HPV genotypes, an appropriate breakdown has been provided. In conclusion, the current prophylactic vaccines against HPV-16 and HPV-18, which have demonstrated good immunogenicity in HIV-infected populations, may still prevent infection and ultimately cancer.

Epidemiology and Molecular Biology of HPV Variants in Cervical Cancer: The State of the Art in Mexico.

Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including those of the anus, oropharynx, and penis are also related to HPV infection. In CC, HPV-16 is the most prevalent high-risk HPV type, followed by HPV-18, both being responsible for 70% of cases. HPV intratype variant lineages differ in nucleotide sequences by 1–10%, while sublineages differ by 0.5–1%. Several studies have postulated that the nucleotide changes that occur between HPV intratype variants are reflected in functional differences and in pathogenicity. Moreover, it has been demonstrated that HPV-16 and -18 intratype variants differentially affect molecular processes in infected cells, changing their biological behavior that finally impacts in the clinical outcome of patients. Mexico has participated in providing knowledge on the geographical distribution of intratype variants of the most prevalent HPVs in premalignant lesions of the cervix and cervical cancer, as well as in other HPV-related tumors. In addition, functional studies have been carried out to assess the cellular effects of intratype variations in HPV proteins. This review addresses the state of the art on the epidemiology of HPV-16 and HPV-18 intratype variants in the Mexican population, as well as their association with persistence, precancer and cervical cancer, and functional aspects related to their biological behavior.

Identifying risk factors for post-operative bleeding in women undergoing loop electrosurgical excision procedure for cervical dysplasia.

Loop electrosurgical excision is a procedure utilised in the treatment of high-grade squamous intraepithelial lesion (HSIL) of the cervix. Post-operatively women may experience immediate and/or delayed per vaginal bleeding. The objective of this prospective pilot study was to assess the feasibility of identifying and quantifying patients' subjective experiences of post-operative bleeding following a loop electrosurgical excision procedure (LEEP) for HSIL. In addition, an analysis of demographical, lifestyle and surgical factors was undertaken to assess for any statistically significant correlation with post-operative bleeding. This study included 110 patients who underwent a LEEP for biopsy-proven or suspected HSIL between 2017 and 2020. Subjective data were collected from weekly post-operative surveys and correlated with procedural data. Primary outcome assessed was the subjective rate of bleeding experienced. Baseline demographics were age, body mass index (BMI), specimen size, human papilloma virus variant and histopathology. Other variables of interest collected were exercise intensity, and alcohol intake. No association of statistical significance was discovered between age, BMI, or day of menstrual cycle. There was a statistically significant association between exercise intensity or specimen size (greater than the median) and increased bleeding, primarily in the first 2 weeks. Women who undergo intense or prolonged exercise in the post-operative period may experience heavier bleeding particularly in the first 2 weeks post-LEEP. Heavy bleeding was also associated with a larger specimen size. There was no correlation between BMI, age or any other demographical factor.

Skin Cancer Back to Basics

ABSTRACT Anogenital squamous cell carcinoma is rare but an often-invasive malignancy that is becoming an increasingly prevalent public health problem. Infection with high-risk human papillomavirus variants plays a critical role in disease progression and occurrence. Immunosuppressive treatment, positive HIV status, number of sexual partners, and history of smoking increase neoplastic progression. Early diagnosis and treatment are pivotal in managing anogenital malignancies to improve quality of life and minimize extensive surgical excision. This article reviews lesion categorization, epidemiology, human-papillomavirus-driven dysplastic epithelial changes, risk factors, diagnostic criteria, treatment options, and prophylactic measures to improve patient outcomes.

Ancient Evolutionary History of Human Papillomavirus Type 16, 18 and 58 Variants Prevalent Exclusively in Japan.

Human papillomavirus (HPV) is a sexually transmitted virus with an approximately 8-kilo base DNA genome, which establishes long-term persistent infection in anogenital tissues. High levels of genetic variations, including viral genotypes and intra-type variants, have been described for HPV genomes, together with geographical differences in the distribution of genotypes and variants. Here, by employing a maximum likelihood method, we performed phylogenetic analyses of the complete genome sequences of HPV16, HPV18 and HPV58 available from GenBank (n = 627, 146 and 157, respectively). We found several characteristic clusters that exclusively contain HPV genomes from Japan: two for HPV16 (sublineages A4 and A5), one for HPV18 (sublineage A1) and two for HPV58 (sublineages A1 and A2). Bayesian phylogenetic analyses of concatenated viral gene sequences showed that divergence of the most recent common ancestor of these Japan-specific clades was estimated to have occurred ~98,000 years before present (YBP) for HPV16 A4, ~39,000 YBP for HPV16 A5, ~38,000 YBP for HPV18 A1, ~26,000 for HPV58 A1 and ~25,000 YBP for HPV58 A2. This estimated timeframe for the divergence of the Japan-specific clades suggests that the introduction of these HPV variants into the Japanese archipelago dates back to at least ~25,000 YBP and provides a scenario of virus co-migration with ancestral Japanese populations from continental Asia during the Upper Paleolithic period.

Genetic diversity in L1 ORF of human papillomavirus in women with cervical cancer with and without human immunodeficiency virus in Botswana and Kenya

BackgroundThe variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Nucleotide changes within the L1 gene, nucleotide variability, and phylogeny were explored in relation to HIV in samples from Botswana and Kenya.MethodsA total of 98 HPV-positive cervical samples were sequenced to identify different HPV variants. Phylogenetic inferences were used to determine HPV genotypes and investigate the clustering of sequences between women living with HIV (WLWHIV) and -women not living with HIV (WNLWHIV).ResultsOut of 98 generated sequences, 83.7% (82/98) participants had high-risk (HR) HPV genotypes while 16.3% (16/98) had low-risk (LR) HPV genotypes. Among participants with HR-HPV genotypes, 47.6% (39/82) were coinfected with HIV. The prevalence of HR-HPV genotypes was statistically higher in the Botswana population compared to Kenya (p-value < 0.001). Multiple amino acid mutations were identified in both countries. Genetic diversity differed considerably among WLWHIV and WNLWHIV. The mean pairwise distances between HPV-16 between HIV and HIV/HPV as well as for HPV-18 were statistically significant. Six (6) new deleterious mutations were identified in the HPV genotypes based on the sequencing of the L1 region, HPV-16 (L441P, S343P), HPV-18 (S424P), HPV-45 (Q366H, Y365F), and HPV-84 (F458L). The majority of the patients with these mutations were co-infected with HIV.ConclusionsGenomic diversity and different genomic variants of HPV sequences were demonstrated. Candidate novel mutations within the L1 gene were identified in both countries which can be further investigated using functional assays.

Genetic Diversity of HPV 16 and HPV 18 Based on Partial Long Control Region in Iranian Women.

Background Human papillomavirus (HPV) 16 and HPV 18 account for 75% of all cervical cancers. The L1 gene, encoding the major surface protein (MSP), is used to classify HPV types (lineages and sublineages), genotypes, and intratypic variants. Therefore, this study aimed to investigate the lineages, sublineages, genetic variabilities, and mutation effects on transcription factor binding sites by using partial sequences of the HPV 16 and HPV 18 long control regions (LCRs) in these samples. Materials and Methods After DNA isolation from 56 positive samples, the LCR of HPV 16 and HPV 18 were amplified using specific primers, and phylogenetic trees were drawn through MEGA X. Compared to the reference sequences, single nucleotide polymorphisms (SNPs) were identified. The transcription binding sites were also evaluated using the online PROMO database. Results The LCRs of 52 samples were successfully sequenced. Overall, 81.58% of all HPV 16 variants belonged to the D1 sublineage, followed by A4 (13.16%), A1 (2.63%), and C1 (2.63%) sublineages. All HPV 18 isolates belonged to A sublineage, 92.85% to A3 sublineage, and 7.15% to A4 sublineage. Out of 27 SNPs in the HPV 16 LCR, A7382T, T7384G, C7387T, C7393G, A7431G, T7448C, and C7783A were HPV 16-specific. Also, among 14 SNPs in the HPV 18 LCR, C7577A and A7943T were not previously reported. An insertion (C) between 7432 and 7433 positions was identified in all studied HPV 16 variants. Besides, most of the HPV 16 mutations were embedded in the YY1, TFIID, Oct-2, and NF-1 binding sites, while c-Fos and MBF1, as the most common binding sites, were affected by HPV 18 LCR mutations. Conclusion The present results showed that D1 and A3 were the dominant sublineages of HPV 16 and HPV 18, respectively. Therefore, women infected with these variants need to be examined in further longitudinal studies to obtain more information about the oncogenic potential of these dominant variants in Iran. Besides, YY1, TFIID, Oct-2, NF-1, c-Fos, and MBF1 were the most frequent binding sites, which were influenced by the mutations.