High-risk Oncogenic Human Papillomavirus Research Articles

Genital infections in high-risk human papillomavirus positive Paraguayan women aged 30-64 with and without cervical lesions.

To determine the prevalence of genital infections (GIs), including sexual transmitted STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and opportunistic pathogens that generally do not cause STIs, non-classic STI: Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis, in women with high-risk oncogenic human papillomavirus (hr-HPV) infection and their association with cervical lesions. A cross-sectional study was carried out including 231 hr-HPV positive women. Of these, 46 has histologically confirmed cervical intraepithelial neoplasia 3 (CIN3) or more (including CIN3 and cervical cancer lesions-CIN3+). GIs were detected by multiplex real time PCR. Odds ratios (OR) were estimated to explore possible associations between GIs and the presence or absence of CIN3+ lesions. Additionally, we examined associations between sociodemographic, sexual, and clinical characteristics and the presence of GIs. In total, there were 174/231 cases of GIs corresponding to an overall prevalence of 75.3% (95%CI: 69.4-80.4), being non-classic STIs the most common (72.3%) compared to STIs (12.6%). The most prevalent non-classic STI and STI were U. parvum (49.8%) and C. trachomatis (7.4%), respectively. The odds of presenting GIs were 3 times higher in women under 46 years compared to older counterparts (OR: 3.32, 95%CI: 1.74-6.16), and in women with a normal Pap smear with inflammation compared to those without inflammation (OR: 3.31, 95%CI: 1.15-9.77). GIs were equally present in women with and without CIN3+ lesions. We observed an association of GIs with inflammation in the Pap smear, but no association with CIN3+, as some of them are very common and likely part of the normal vaginal flora, suggesting that such infections do not appear to be cofactors in cervical carcinogenesis, although larger prospective studies are needed.

Abstract PR004: Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients

Abstract Background-Human papilloma virus (HPV-positive (+)) oropharynx cancer (OPC) are a distinct neoplastic entity associated with a significant survival advantage compared to HPV- OPCs. The survival advantage is so great that the presence of regional cervical lymph node metastasis is no longer considered an advanced stage III/IV cancer. The survival advantage associated with HPV+ OPC is not the same for Black patients compared to all other races and emerging data now suggests Black patients with HPV+ OPC have survival outcomes similar to White patients with HPV- OPC. We conducted a differential gene expression analysis and high-risk HPV serotyping comparing genomic difference between treatment naïve Black and White patients with HPV+ OPC. Methods: Surgical samples were obtained from Duke, the University of Texas Medical Branch, and the University of Mississippi, through an IRB approved protocol. HPV status determined by p16 immunohistochemistry (IHC). We performed digital spatial profiling and conducted a differential gene expression analysis in 14 Black and 13 White patients using the Nanostring™ Whole Transcriptome Atlas. Morphology markers included CD45, PANCK, and alpha SMA to label lymphocytes, epithelium, and stroma, respectively. A component of the bioinformatics pipeline included conducing a KEGG pathway analysis using pre-ranked test statistics from self-reported Black and White patients HPV+ OPC. The presence of high-risk oncogenic HPV was determined in parallel by RT-PCR (Creative Biogene). P16, CD68 and CD3 expression was measured by IHC using standard techniques. Results: There was a significant decrease in antigen processing and presentation and T-cell receptor signaling pathways in CD45+ lymphocytes (p<0.0002) and B-Cell receptor and chemokine signaling pathways in PANCK+ tumor epithelial cells (p<0.03) in Black patients compared to White patients with HPV+ OPC. There was a significant difference in p16 expression and the absence of HPV DNA in Black patients compared to White patients (p<0.017). 32% of Black patients with p16+ OPC were HPV DNA negative. There was no p16/HPV16 DNA discordance observed in the White patient cohort. Three patients were co-infected with other carcinogenic HPV serotypes (45, 51, and 59) in addition to HPV16 (two Black and one White). CD68 expression, associated with M1-like anti-tumor macrophages, was significantly decreased in Black patients with p16+/HPV16+ OPC, compared to White patients (p<0.017), suggesting alterations in tumor immune response may be important in cancer disparities. Conclusion: The favorable prognosis associated with HPV+ OPC, including recruitment in currently ongoing radiation de-escalation clinical trials cannot be widely applied to all patients with HPV+ OPC and studies addressing racial disparities, HPV/p16 discordance, and predictors of poor response represent a significant health equity gap in the field of OPC disparities. Citation Format: Tammara L. Watts, Katerine Gonzalez, Xiangfeng Shen, Layne Rogers, Nosa Osazuwa-Peters, Gina D. Jefferson, Cecilia G. Clement, Danielle Range, Russel R Kahmke, Walter T Lee, Daniel J. Rocke, Trinitia Y Cannon, Yvonne Mowery, Kouros Owzar. Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR004.

HUMAN PAPILLOMAVIRUS, CLINICAL, DERMATOLOGICAL AND GYNECOLOGICAL APPROACH

Introduction: Human papillomavirus (HPV) infection is associated with a wide range of cutaneous and mucosal manifestations. The spectrum of HPV ranges from inapparent infections, through multiple benign clinical presentations, including cutaneous and mucosal disease, to malignant and premalignant conditions. Cervical cancer is the fourth cancer with the highest incidence in women in the world, being the second cause of cancer death in women between 15 and 44 years of age, one of the risk factors for this cancer is the human papillomavirus. Objective: to detail the current information related to human papillomavirus, description, etiology, epidemiology, pathophysiology, anamnesis, physical examination, evaluation, treatment, differential diagnosis, prognosis, prevention and complications taking into account a clinical, dermatological and gynecological approach. Methodology: a total of 27 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 18 bibliographies were used because the other articles were not relevant for this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: human papillomavirus, HPV, dermatosis, warts, infection, papanicolau, tumor virus infections. Results: HPV has been associated with the development of laryngeal, mouth, lung and anogenital cancers. Subtypes 6 and 11 are low risk and are usually associated with the formation of condylomas and low-grade precancerous lesions. Subtypes 16 and 18 are high-risk and are responsible for high-grade intraepithelial lesions that progress to malignant neoplasia. There are more than 180 HPV subtypes.The prevalence of genital HPV in adults aged 18-59 years is about 45.2% in males and 39.9% in females. The prevalence of high oncogenic risk HPV genotypes is 2.26%; (95%CI: 1.75-2.78), with the most common genotype being 16 (28.89%). Cervical cancer screening with cytology has significantly reduced the incidence and mortality of this type of cancer in developed countries, despite the fact that its sensitivity for detecting CIN2+ is around 66%. Conclusions: it is of remarkable importance to know the human papillomavirus outlook, especially because it is linked to a number of underlying clinical manifestations both benign, premalignant and malignant conditions. The authors recommend prevention, especially suggesting that boys and girls be vaccinated against HPV starting at 11 to 12 years of age, in addition to the other measures outlined in the article. It is important to understand that HPV alone does not cause cancer, but requires triggering factors such as smoking, folate deficiency, exposure to ultraviolet light, immunosuppression and pregnancy. Individuals with cutaneous warts have numerous treatment alternatives available, including surgical removal, cryotherapy, irritant or immunomodulatory drugs, and laser removal. KEY WORDS: HPV, infection, pap smear, warts.

Colposcopically Directed Biopsy Before Ablative Treatment Versus Direct Ablative Treatment in Patients With Cervical Oncogenic HPV.

In the past, the standard of care for women with abnormal cervical cytology has been the performance of colposcopically guided biopsy, followed by conization or large loop excision of the transition zone (LLETZ) where biopsy revealed pre-cancerous or cancerous areas. More straightforward protocols are emerging which advocate performing LLETZ in all women with highly suspicious cytology, suspicious colposcopic impression, or the presence of high-risk oncogenic human papilloma virus (HPV) strains in their cervical swabs. This, theoretically, would reduce the rate of false-negative diagnoses, but at the price of overtreating a significant number of healthy women. We retrospectively analyzed cervical cancer screening protocols in two large cohorts of women with high-risk HPV. The study compared outcomes between patients undergoing a colposcopically directed biopsy before LLETZ (n=683) and those proceeding directly to LLETZ without a biopsy (n=136). The primary focus was to assess whether intervening biopsies would reduce unnecessary ablative procedures without compromising the detection of high-grade lesions. The biopsy group had a high false-negative rate, with several high-grade lesions (CIN3) and a case of invasive cancer initially underdiagnosed. Conversely, the direct-to-LLETZ approach, while ensuring no high-grade lesions were missed, led to overtreatment of lower grade lesions. These findings raise concern about the reliance on biopsy results for treatment decisions. Neither protocol was entirely satisfactory, although the more aggressive one avoided the potentially life-threatening consequence of false-negative results. Further research is mandatory to accurately diagnose all cases requiring aggressive treatment, without subjecting healthy women to ablative treatments they do not need.

P16 overexpression identifies oncogenic high-risk HPV infection in non-oropharyngeal squamous cell carcinoma of the head and neck.

Human papillomavirus (HPV) is an increasing risk factor for cancer. HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC. In oral and laryngeal squamous cell carcinoma (OSCC/LSCC), the relevance of p16 immunohistochemistry, alone or in combination with other cell cycle-related proteins, to identify HPV-driven non-OPSCC is less well understood. We stained for p16, pRb, cyclin D1, and p53 in 327 HNSCC. In 310 OPSCC, HPV-status was assessed by HPV DNA PCR. In 119 non-OPSCC, RNA in situ hybridization was additionally performed. HPV-status was correlated with staining patterns, p53 and clinical data. The OPSCC showed blockstaining for p16 in 36%, 8% were equivocal. Of these, HPV-testing was performed in 57%, and 53% were positive for HPV DNA. HPV-association correlated with absence of pRb and cyclin D1 and favorable outcome. In non-OPSCC, 18% showed p16-blockstaining, and 13% showed E6/E7 RNA. Six of seven HPV+ OSCC and 8/8 LSCC lost pRb and cyclin D1. Compared to HPV-negative counterparts, patients with HPV+ cancers had lower rates of alcohol consumption and keratinizing morphology. HPV-positive OSCC had a longer overall survival (p < 0.05). HPV subtype 16 was the most common. We conclude that HPV-positive non-OPSCC are associated with p16 overexpression and low levels of pRb and cyclin D1. High expression of pRb and cyclin D1 indicates HPV-negativity.

Сучасні аспекти клініки, діагностики та лікування ВПЛ-асоційованих доброякісних уражень ротової порожнини

Human papillomavirus (HPV) exhibits specific tropism for squamous epithelium and therefore contributes to the development of many benign, potentially malignant, and malignant epithelial lesions. The benign HPV-related lesions of the oral cavity comprise verruca vulgaris, squamous papilloma, condyloma acuminatum and multifocal epithelial hyperplasia. Oral squamous papilloma is most common in people of various ages. Purpose: To determine the structure, clinical features and morphological signs of oral squamous papilloma in patients of different sex and age. Materials and methods. For the period of 2020-2023, 18 people with oral papilloma (papillomatosis) aged 15 to 70 years were examined. In 12 patients, papilloma was removed by conventional surgery, in 6 patients – using a high power diode laser. Pathohistological evaluation of excisional biopsy and identification/genotyping of HPV DNA by REAL TIME PCR was carried out. Results. Squamous papilloma dominates in the structure of HPV-related benign oral lesions (88.8%). Among patients with papiloma, the majority are women (72.2%) with an average age of 29.3±4.0 years. The average age of men with papilloma is 52.2±5.8 years. By localization in the oral cavity, papillomas are most often found on the gingiva (43.75%), as well as on the tongue (25%), on the soft palate (18.75%), on the mucous membrane of the upper lip (6.25%) and cheek (6.25%). The average papilloma size by diameter was 0.71±0.06 cm. Pathomorphological confirmation of the impact of HPV on the development of oral squamous papilloma, namely the presence of coylocytes, was obtained in 31.3% of excision biopsies. Hyperkeratosis of the covering epithelium was found in 5 patients (27.7%), and this condition is defined as «keratopapiloma». In 6 women (33.3%), the presence of various types of HPV was detected by PCR, including high oncogenic risk (HPV-16, 18, 66, 68). Conclusion. Oral squamous papilloma, associated with high oncogenic risk HPV, as well as keratopapilloma in heavy smokers, should be considered a precancerous disease of the oral mucosa with a high risk of malignancy. Key words: human papillomavirus, papillomavirus infection, oral squamous papilloma, keratopapiloma, laboratory diagnostics, oral mucosa, risk of malignancy

Investigating under-reported human papillomavirus genotypes in Grenadian women through self-sampling for cervical cancer screening.

To compare the adequacy, agreement, and acceptability of Papanicolaou testing (cytology) for cervical cancer screening using self-collected samples compared to physician-collected samples in Grenada in the Caribbean. Furthermore, the study identifies the human papillomavirus (HPV) genotypes present among asymptomatic women testing positive for HPV, the etiologic cause of cervical cancer. Participants were divided into two groups and two cervical samples were collected from the women in each group: a self-collected sample and a physician-collected sample. Cervical specimens were tested for cytology and HPV. HPV genotyping was performed on positive specimens. Self-collected samples were adequate and in agreement with physician-collected samples, showing no difference between the two sampling methods. Oncogenic high-risk HPV genotypes were identified in cervical samples which were positive for atypical squamous cells and low-grade squamous intraepithelial lesions. The high-risk HPV genotypes found, notably HPV 45 and 53, differed from those most commonly reported. Although the commonly reported high-risk genotypes HPV 16 and 18 were found, so were 31, 33, 35, 52, 66, 68, and 82. Using self-collection facilitated the discovery of unexpected HPV genotypes among asymptomatic women in Grenada. These findings add new information to the literature regarding cervical cancer and neoplasia screening and HPV genotypes in the Caribbean. This genotype information may impact surveillance of women with low-grade lesions, HPV vaccine selection, and possibly further vaccine research. Research regarding HPV in Caribbean pathology samples of cervical neoplasia and cancer is needed.

Computational and AI-driven 3D structural analysis of human papillomavirus (HPV) oncoproteins E5, E6, and E7 reveal significant divergence of HPV E5 between low-risk and high-risk genotypes

There are over 220 identified genotypes of Human papillomavirus (HPV), and the HPV genome encodes 3 major oncogenes, E5, E6, and E7. Conservation and divergence in protein sequence and function between low-risk versus high-risk oncogenic HPV genotypes has not been fully characterized. Here, we used modern computational and structural folding algorithms to perform a comparative analysis of HPV E5, E6, and E7 between multiple low risk and high risk genotypes. We first identified significantly greater sequence divergence in E5 between low- and high-risk genotypes compared to E6 and E7. Next, we used AlphaFold to model the structure of papillomavirus proteins and complexes with high confidence, including some with no established consensus structure. We observed that HPV E5, but not E6 or E7, had a dramatically different 3D structure between low-risk and high-risk genotypes. To our knowledge, this is the first comparative analysis of HPV proteins using Alphafold artificial intelligence (AI) system. The marked differences in E5 sequence and structure in high-risk HPVs may contribute in important and underappreciated ways to the development of HPV-associated cancers.

High-risk human papillomavirus: prevalence, association with clinical and morphological characteristics of invasive cervical cancer

Purpose of the study. Analysis of contemporary literature sources dedicated to the study of characteristics of high oncogenic risk human papillomavirus (HPV), associative links of the virus’s molecular-genetic parameters with the clinical and morphological characteristics of invasive cervical cancer (ICC).Materials and methods. A literature search was conducted in electronic databases including the National Center for Biotechnology Information Search database (PubMed/Medline), ResearchGate, Scopus, Web of Science, Cancer Tomorrow, Global cancer observatory, Cochrane Library, eLIBRARY, DisserCat. The search covered the period from 1990 to 2022 and utilized keywords in Russian and their English translations: cervical cancer, high oncogenic risk HPV, HPV status, HPV genotype, multiple infections, DNA integration, viral load. More than 120 full-text sources were studied, in which the analysis of possible correlations between the parameters of human papillomavirus infection and the clinical and morphological characteristics of cervical cancer was carried out. In review included data from 57 publications. Results. According to most authors, more than 88 % of patients with invasive ICC are HPV-infected. The etiological structure is dominated by HPV 16 (70–72 %), 18 (13–15 %), and 45 (5–7 %) types. Non-detection of HPV HR in cervical cancer is associated, including with a false negative result of the study.The literature analysis showed the presence of an association between HPV status and age, morphological form of the tumor, viral load, high oncogenic risk HPV genotype, presence of deep stromal invasion, and metastatic involvement of lymph nodes. With regard to such molecular genetic parameters of HPV HR as viral load and HPV DNA integration, associative relationship with prognostic important clinical indicators of cervical tumor – the stage of the disease, the loco-regional prevalence of the tumor process, the histological type of tumor – remains the subject of discussion.Conclusion. Many publications report a correlative link between HPV status and high oncogenic risk HPV genotype with such an important factor affecting ICC treatment outcomes as the morphological form of the tumor. Ambiguous conclusions on the presence of an association between a number of molecular-genetic parameters of HPV infection with the main prognostic factor – stage of the disease (due to the heterogeneity of samples, the use of different test systems, and the insufficiently complete account of the main parameters of HPV infection, especially data on viral DNA integration), make it advisable to conduct further research on a representative group of patients with homogeneous diagnostic protocols to determine the most complete spectrum of parameters of high oncogenic risk HPV. In addition, the conducted literature analysis showed the promise of searching for predictors of the effectiveness of specialized treatment of patients with ICC among such HPV infection parameters as HPV status, high oncogenic risk HPV genotype, and the significantly associated physical status of viral DNA.

The Prevalence of Human Papillomavirus in Women Living with HIV in Mukono General Hospital, Uganda

Background and aims: High-risk oncogenic genotype human papillomavirus (HPV) infection induces cervical cancer (CaCx), a common cancer in women globally. Women living with human immunodeficiency virus (WLHIV) have a greater risk of hr-HPV infection and perseverance, enhancing the risk of defects in the cells of the cervix and aggressive CaCx. However, its prevalence in WLHIV is not apparent. The main objective of this research was to explore the types and prevalence of HPV infection by genotyping HPV among a cohort of WLHIV attending an antiretroviral therapy (ART) clinic in Mukono, Uganda. Methods: A cross-sectional study was conducted among women aged 25 to 49 years attending an ART clinic in a public health facility in Mukono, Uganda. Systematic random sampling was used to select 342 WLHIV from a target population of 3000. Only participants who had an Xpert HPV test between July 2021 and December 2022 were selected and interviewed, and their responses were analyzed using descriptive statistics. Results: Slightly more than half (56.7%) of the participants were under 35 years old, married (52.6%), and with a primary level of education (51.2%). The prevalence of hr-HPV was 39.8% (95% CI: 34.40-44.78). Of the total participants, 136 (39.8%) were high-risk HPV positive, with HPV 16, HPV18/45, and other hr-HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) being positive in 23 (6.7%), 21 (6.1%), and 110 (32.2%), respectively, while 17 (12.5%) had mixed hr-HPV infections. Conclusion: There is a high prevalence of HPV infection among WLHIV, underscoring the need to frequently screen and diagnose CaCx pre-cancerous lesions for its effective prevention.

HPV and Systemic Response in Cervical Intraepithelial Neoplasia

Objectives: to verify whether there is an association of low and high-risk HPV with blood count parameters in patients with cervical intraepithelial neoplasia. Methods: We prospectively evaluated 48 patients with Pap smear showing low or high-grade intraepithelial lesion, submitted to collection of material to perform PCR for high-risk and low-risk HPV. The following blood count parameters were evaluated: hemoglobin, red blood cells, hematocrit, absolute number of leukocytes, neutrophils, lymphocytes, eosinophils, basophils, monocytes and platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and Red Cell Distribution Width (RDW). Receiver operating characteristic (ROC) curve was used to obtain the area under the curve (AUC) relating the positivity or not of HPV with the blood count parameters evaluated. Mann-Whitney test and multivariate analysis were performed, with level of significance less than 0.05. Results: Relating the positivity or not of HPV with the blood count parameters (Roc curves), there was statistical significance only between high-risk HPV and the platelet count (sensitivity=75%, specificity=66.7%, AUC=0.674, p=0.039). Platelet count ≤ 177,000/mm3 is associated with high-risk HPV. Subsequently, the multivariate analysis was performed, and the absolute value of platelets was considered an independent variable in this association with high-risk oncogenic HPV. Conclusion: A systemic response is found with the presence of high-risk HPV in CIN. Thus, platelet count ≤ 177,000/mm3 is associated with high-risk HPV.

Human papillomavirus positivity and cervical lesions in relation to HIV infection: a comparative assessment in the Cameroonian female population.

Cervical lesions, induced by high-risk oncogenic human papillomavirus (HR-HPV), in the context of HIV remains a global health challenge. We determined the effect of HR-HPV on the development of cervical lesions in women with and without HIV infection. A cross-sectional analytical study was conducted among 257 women living in Cameroon. HIV serology, HR-HPV genotyping and cervico-vaginal smear (CVS) were performed for all participants; among those declared HIV positive, plasma HIV viral load and CD4 count were measured. Statistical analyses were performed using Graph Pad version 6.0; P#x003C;0.05 was considered statistically significant. The mean age of the participants in our study was 37±6.5 years. According to HIV serology, 184 (71.59%) were HIV-positive vs. 73 (28.40%) HIV-negative. Among the HIV-positive women, the median CD4 count was 438 [IQR: 317-597] cells/mm3 and the median viremia was #x003C;40 [IQR: #x003C;40-2318] copies/ml. After successful genotyping, the prevalence of HR-HPV was 36.32% (73/201), with a significantly higher proportion in HIV-infected individuals (41.98% (55/131) vs. 25.71% (18/70); P=0.02; OR=2.1). The overall rate of cervical lesions was 23.34% (60/257), with a non-significantly higher proportion in HIV-infected participants (25.00% (46/184) vs. 19.17% (14/73); P=0.31). Relevantly, the presence of HR-HPV was significantly associated with cervical lesions (P#x003C;0.0001; OR=5.07), with a higher odds of cervical lesion in HIV-positive individuals (P#x003C;0.0001 and OR=5.67) compared to HIV-negative individuals (P=0.03 and OR=3.83). Although oncogenic HPV appears to be an independent factor in the development of cervical lesions, this study reveals higher odds of cervical lesions among HIV/HPV co-infection than in HPV infection alone.

The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer

ABSTRACT Infection with high-risk human papillomavirus (HPV), for example, with types 16 and 18, is closely associated with cervical cancer development, which continues to threaten women’s health globally. Although HPV oncogenes have been recognized as the main cause of transformation of normal cervical epithelial cells, non-coding RNA could also be involved in the initiation and promotion of cervical cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-documented long non-coding RNA (lncRNA), has been previously reported to exert roles in HPV-positive cervical cancer; however, the detailed underlying mechanism has yet to be investigated. In the present study, high expression levels of MALAT1 in HPV-Positive Cervical Cancer cells were confirmed, and silencing MALAT1 resulted in decreased rates of cell proliferation, migration, and invasion, both in vitro and in a zebrafish xenograft tumor model. Moreover, the results obtained showed that silencing MALAT1 led to down-regulation of the N6-methyladenosine (m6A) demethylase ALKBH5 via regulating miR-141-3p expression, which caused a decrease in the expression levels of matrix metalloproteinase 2 (MMP2) and MMP9 expression, thereby suppressing cell migration and invasion. Taken together, the results obtained have suggested that the MALAT-ALKBH5 signaling axis may be activated in HPV-positive cervical cancer cells, which could contribute to cell proliferation and metastasis through the regulation of key genes, such as MMP2 or MMP9. The findings of the present study should both help to improve our understanding of the underlying tumorigenic mechanisms of HPV-positive cervical cancer and be of further use in the development of potential therapeutic drugs.

The genetic variant rs55986091 HLA-DQB1 is associated with a protective effect against cervical cancer.

Cervical cancer (CC) is a prevalent malignancy affecting women globally. The primary causative factor of CC is the high-risk oncogenic human papillomavirus (HR-HPV). However, it is noteworthy that not all women infected with HR-HPV develop cancer, indicating the potential involvement of genetic predisposition in the development of CC. This study aims to identify genetic risks and their distribution in groups of women with different epidemiological features of HR-HPV. A comparison was conducted among four groups of women, comprising 218 HPV-negative women, 120 HPV-positive women, 191 women diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or 3, and 124 women diagnosed with CC. The analysis focused on four single nucleotide polymorphisms (SNPs): rs55986091 in HLA-DQB1, rs138446575 in TTC34, rs1048943 in CYP1A1, and rs2910164 in miRNA-146a. The rs55986091-A allele exhibited a protective effect within the "CC" group when compared to the "HPV-Negative" group (OR = 0.4, 95% CI= 0.25-0.65) using a log-additive model. Additionally, similar protective effects were observed in the "CIN 2/3" group compared to the "HPV-Negative" group (OR = 0.47, 95% CI = 0.28-0.79). The data obtained emphasize the importance of developing PCR-based diagnostic kits for the identification of SNP alleles, particularly for rs55986091, among HR-HPV-positive women within the Russian population.

HPV vaccination in Kenya: a study protocol to assess stakeholders' perspectives on implementation drivers of HPV vaccination and the acceptability of the reduced dose strategy among providers.

Cervical cancer is the leading cause of cancer-related deaths among Kenyan women. Persistent infection with high-risk oncogenic Human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. HPV vaccines are safe, durable, and efficacious in preventing incident HPV infections. In Kenya, despite efforts to increase HPV vaccination, coverage remains low. We sought to assess: (1) barriers and facilitators of HPV vaccination from the perspective of adolescent girls and young women (AGYW), their guardians as well as stakeholders involved in HPV vaccine delivery, and (2) the acceptability of the single dose of the HPV vaccination among healthcare providers (HCPs). Our study is nested within the KENya Single-dose HPV-vaccine Efficacy study (KEN SHE) that sought to test the efficacy of single-dose bivalent (HPV 16/18) and single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination. We are conducting this study in Kiambu, Nairobi, and Kisumu counties. In these counties, we are interviewing stakeholders (n = ∼25), selected based on their role in HPV vaccination at the county and national levels. Interviews are audio recorded and conducted in English or Swahili. The semi-structured interview guides were designed based on: (1) the Theoretical Domains Framework (TDF) for AGYW and guardians and (2) the Consolidated Framework for Implementation Research (CFIR) for other stakeholders. The Theoretical Framework of Acceptability (TFA) was leveraged to design the survey administered to HCPs (n = ∼309) involved in HPV vaccination. We will develop a codebook based on emerging codes from the transcripts and constructs from the TDF and CFIR. Emerging themes will be summarized highlighting similarities and differences between and within the different stakeholder groups and counties. Descriptive statistics and a χ2 test will be used to assess the distribution of responses between the different sites and regression analysis will be used to assess factors associated with high acceptability of the single-dose strategy while controlling for confounding variables. Our study will describe key barriers and facilitators that affect HPV vaccination from the perspective of multiple stakeholders as well as insights on the perspective of HCPs towards the single-dose strategy to inform the designing of strategies to increase HPV vaccination uptake in Kenya and comparable settings.

Modern concepts in cervical carcinogenesis

The article discusses modern ideas about cervical carcinogenesis as a multi-stage process of multifactorial genesis. Currently, ideas about the pathogenesis of cervical cancer (CC) are based not only on understanding the role of high-risk oncogenic human papillomavirus (HPV) in this process and accumulation of genetic changes caused by it, but also on formation of a complex HPV interactome, or a network of intermolecular interactions of HPV oncoproteins with host cell proteins. Carcinogenesis also involves a wide range of epigenetic events and, above all, impairment of the regulatory function of miRNAs. An important role in cervical carcinogenesis is attributed to the concept of cancer stem cells (CSCs) formulated in recent years, which is closely related to the explanation of disease recurrence and treatment resistance, as well as to new approaches to treatment. The cervicovaginal microbiome and cervical microenvironment, which are responsible for natural clearance of HPV, regression of epithelial lesions, and modeling of the immune response, are becoming promising objects for research.The aim of the review was to present up-to-date information on the most important mechanisms of cervical carcinogenesis, as well as on new approaches to the treatment of CC, based, in particular, on the use of knowledge about regulatory miRNAs, CSC markers, and the state of the cervicovaginal microbiota.

Evaluation of the prevalence of HPV from environmentally unfavorable districts of the Republic of Karakalpakistan.

e17526 Background: Identification of HPV-positive women in the Aral regions of the Republic of Karakalpakstan and the city of Chirchik, Tashkent region. Methods: The study included 48,788 women aged 30-55 years.The project was approved by the Ministry of Health of the Republic, covering 10 districts, mainly near the Aral Sea: Khojeyli, Kanlykul, Shumanay, Chimbay, Karauzyak, Kungrad, Kegeili, Muynak, Buzatau, Nukus district. The Xpert HPV Assay is a qualitative in vitro diagnostic test for the detection of the E6/E7 region of high oncogenic risk human papillomavirus (HPV) genomic DNA in patient specimens. The analysis was performed on a Cepheid Gene Xpert system. The Xpert HPV test specifically identified HPV 16 and HPV 18/45 types in two separate detection channels and reported the presence of 11 other high risk virus types (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68) as a combined result. Results: Of these, HPV was detected in 3304 (6.8%) women, HPV-negative women were 45.484 (93.2%). Distribution by HPV types: among HPV-positive women HPV 16 - 28%; HPV 18.45-7.6%; HPV 31.33.35.52-23.9%; HPV 51-11.6%; HPV 39.56.66-18.4%; mixed forms - 10.2%. Erroneous tests were 2.9%. The age of HPV positive women was 35-45 years. Conclusions: In the studied regions, HPV types 16,31,33,35,52 were most often detected, which should be taken into account when developing the country's national screening program. Also, given the age-specific prevalence of HPV, may be considered for the target group of cervical cancer screening of women aged 35 and 45 years, which is more acceptable for a developing country.

Characterization of the oral microbiota among middle-aged men with and without human papillomavirus infection

ObjectivesTo characterize the oral microbiota among middle-aged men and identify differences between men with a prevalent oral high-risk (oncogenic) HPV infection and those without. Materials and MethodsThis was a case-control study nested within a prospective screening study for HPV-related cancers among middle-aged men. 16S rRNA sequencing was used to characterize the oral microbiota and the cobas HPV Test was used to detect presence of oral high-risk HPV types. We determined the overall composition of the oral microbiota and assessed differences in relative abundance of bacterial taxa as well as alpha and beta diversity among men with a prevalent oral high-risk HPV infection compared to men who were HPV-negative. ResultsAmong 13 high-risk HPV-positive and 30 HPV-negative men, we found significant differences in beta diversity but not alpha diversity. Fretibacterium, F0058, Kingella, Treponema, and Prevotella were more abundant among the high-risk HPV-positive men while Neisseria and Lactobacillus were more abundant among the HPV-negative men. ConclusionThis study adds to the evidence that the oral microbiota varies according to oral HPV infection status and may be associated with the natural history of oral HPV infection.

Prevalence of oral HPV among people living with HIV (PLHIV) in Pune, India

Background: People living with HIV (PLHIV) are at an increased risk of human papillomavirus (HPV)-related head and neck cancers (HNCs). However, there is little data on the prevalence of oral HPV among PLHIV in India, limiting the planning of oral HPV preventive strategies. Methods: We used cross-sectional data from an oral cancer screening study conducted at the antiretroviral therapy (ART) centre of Byramjee-Jeejeebhoy Government Medical College-Sassoon General Hospitals (BJGMC-SGH). PLHIV ≥21 years of age with no prior history of HNCs were enrolled. We determined the prevalence of high-risk oncogenic HPV (hrHPV) and low-risk non-oncogenic HPV (lrHPV) using real-time PCR and Next-Generation Sequencing. We used multinomial logistic regression to determine the prevalence ratios (PRs) of different sociodemographic, clinical, and behavioural predictors with hrHPV and lrHPV. Multivariable models were adjusted for age, sex, CD4 count and duration on ART. Results: Of the 582 PLHIV enrolled, the median age was 40 years (IQR: 34–46) and 54% were male. More than a fourth (25.8%) had multiple sexual partners and 11% had given oral sex. Median CD4 counts were 510 cells/mm3 (IQR: 338–700). The prevalence of hrHPV was 4.5% and lrHPV was 3.4%. Of those with hrHPV, 77% had HPV16. There were no significant associations with any predictors for both lrHPV and hrHPV in adjusted analyses. Conclusions: We found the prevalence of any oral HPV (hrHPV and lrHPV) to be 7.9% among PLHIV in India. Larger studies are required to better understand risk factors for oral HPV among Indian PLHIV.

Type-specific HPV incidence and clinical spectrum of lesions induced by high-risk oncogenic HPV types among study participants in Eastern Uganda

Different studies show that high-risk HPV genotypes are the main etiological agents for cervical cancer development and cancer-related deaths in women worldwide. In Uganda, cervical malignancies due to human papillomavirus (HPV) are predominant among sexually active women. However, data on the incidence and clinical spectrum of lesions associated with high-risk HPV infection is inadequate. The current study was aimed to determine incidence and clinical spectrum of lesions induced by high-risk oncogenic HPV types among study participants in Eastern Uganda. We piloted a prospective follow-up study among 1,077 women aged 15-55 years to assess the incidence and clinical spectrum of lesions associated with human papillomavirus infections (HPV). HPV Real-Time PCR using HPV High-Risk Screen Real-TM Quant 2x kit (Sacace, Biotechnologies, Italy) was used for genotyping high-risk HPV types. Four hundred and sixteen (416) of 1,077 (38.6%) women were monitored for an average time of 18 months (inter-quartile range 9.6-26.6). Forty-three (43) women had incident HPV infections during 214 person-years of follow-up reflecting an incidence rate of 20.1 per 100 person-years. Incident HPV infections were marginally associated with HIV positivity (RR = 3.0, 95% CI: 0.8 - 8.2) and usage of oral contraceptives (RR=2.6, 95% CI: 1.4 - 2.8) but not with the age of study subjects, or number sexual partners. Clearance for high-risk HPV infections was frequently ranging between 37.5% and 100.0% for high-risk types. Only 41.3% of women cleared all their infections. Clearance was associated with HIV negativity (Adjusted clearance = 0.3, 95% CI: 0.2 - 0.8) but not with age at study entry or oral contraceptive usage. Incident HPV infections and clearance of HPV type-specific infections were common among study participants. We also found a high prevalence of high-risk HPV types in cervical lesions, which reveals an association between cervical lesions and high-risk HPV types.