Oncogenic Human Papillomavirus Research Articles

Multinational epidemiological analysis of oral human papillomavirus incidence in 3,137 men.

Oral human papillomavirus (HPV) is associated with oropharyngeal cancer (OPC). Although OPC incidence is increasing globally, knowledge of oral HPV infection rates is limited. Here we carried out an observational epidemiological analysis of oral HPV incidence in 3,137 men enrolled from the United States, Mexico and Brazil between 2005 and 2009. Individuals were followed for new HPV infection for a median of 57 months. Cumulative incidence and factors associated with acquisition were also assessed. The incidence rate of oral oncogenic HPV was 2.4 per 1,000 person-months, did not vary with age and was constant throughout the study period. Risk of oral HPV acquisition was significantly associated with alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment. These data indicate that men are at risk of acquiring oral HPV throughout their lifetime, suggesting that catch-up vaccination may reduce new infection incidence.

247 (PB235): Oncogenic human papillomavirus hijacks p300 to drive viral transcription, creating a therapeutic vulnerability that can be exploited with selective p300/CBP catalytic inhibitors

247 (PB235): Oncogenic human papillomavirus hijacks p300 to drive viral transcription, creating a therapeutic vulnerability that can be exploited with selective p300/CBP catalytic inhibitors

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.

The lncRNA and miRNA regulatory axis in HPV16-positive oropharyngeal cancers

The global rise of oropharyngeal cancers (OPC) associated with the human papillomavirus (HPV) type 16 necessitates a deeper understanding of their underlying molecular mechanisms. Our study utilised RNA-sequencing data from The Cancer Genome Atlas (TCGA) to identify and analyse differentially expressed (DE) long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in HPV16-positive OPC, and to elucidate the interplay within the lncRNA/miRNA/mRNA regulatory network. We revealed 1929 DE lncRNAs and identified a significant expression shift in 37 of these, suggesting a regulatory 'sponge' function for miRNAs that modulate cellular processes. Notably, the lncRNA Linc00911 exhibited decreased expression in HPV16-positive OPC, a change directly attributable to HPV oncogenes E6 and E7 as confirmed by RT-qPCR in cell lines and patient samples. Our comprehensive analysis presents an expansive landscape of ncRNA-mRNA interactions, offering a resource for the ongoing pursuit of elucidating the molecular underpinnings of HPV-driven OPC.

The role of human papillomavirus in laryngeal carcinoma using PCR

<b>Introduction:</b> The etiology of laryngeal carcinoma is multifactorial. Smoking and alcoholism are well-known risk factors; however, recently oncogenic human papillomavirus has been suggested to promote carcinogenesis. PCR has had the most dramatic impact on molecular biology, enabling the amplification of specific regions of interest and detection of gene sequences.<b>Aim:</b> The aims are to evaluate the possible relationship between laryngeal carcinoma and human papillomavirus and its impact on the socio-demographic findings and the clinicopathological presentation.<b>Material and method:</b> Twenty-five patients with laryngeal carcinoma were included. Two biopsies were taken from every patient, the first from the main bulk of the tumor, the second from the normal surrounding mucosal tissues and considered as a control group. Virus detection was done by PCR test. The HPV screen test is an <i>in vitro</i> nucleic acid amplification test for qualitative detection of HPV type (16, 18, 31, 33, 35, 39, 45, 52, 53, 56, 58, 59, 66, and 70) and β-globin gene used as internal control. Samples were transferred into the thermal cycler, in which denaturation, annealing, and chain elongation occurred. Specific bands of HPV were detected using a high-resolution Cannon camera.<b>Results:</b> The average age of the patients was 60.8 years. Twenty-three patients (92%) were males. Viral DNA was detected in 8% of patients, representing genotypes (16, 18, 31, 33, 35, 39, 45, 52, 53, 56, 58, 59, 66, and 70). There is no statistically significant relationship between the presence of the virus and epidemiological and clinic-pathological features except for female gender distribution (P-value = 0.022).<b>Conclusions:</b> There is no significant relationship between laryngeal carcinoma and human papillomavirus, nor a significant impact on socio-demographic findings and clinicopathological presentation.

Prevalence of Anal Human Papillomavirus Infection and Anal High-Grade Squamous Intraepithelial Lesions Among Men Who Have Sex With Men 50 Years and Older Living With or Without HIV.

Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, CA. One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions. Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8-129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.

Comprehensive breast cancer risk analysis with whole exome sequencing and the prevalence of BRCA1 and ABCG2 mutations and oncogenic HPV.

Breast cancer is the most prevalent cancer and also the leading cause of cancer death in women worldwide. A comprehensive understanding of breast cancer risk factors and their incidences is useful information for breast cancer prevention and control planning. The present study aimed to provide information on single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in breast cancer, the allele frequency of two SNPs in breast cancer-related genes BRCA1 DNA repair associated (BRCA1; rs799917) and ATP binding cassette subfamily G member 2 (ABCG2; rs2231142), and the prevalence of human papillomavirus (HPV) infections in a normal population living in Phayao Province, Northern Thailand. One breast cancer and 10 healthy samples were investigated by whole exome sequencing (WES) and compared for genetic variation. The WES data contained SNPs in genes previously implicated in breast cancer and provided data on CNVs. The allele frequencies for SNPs rs799917 and rs2231142 were also examined. The SNP genotype frequencies were 35.88% CC, 46.54% CT, and 17.58% TT for rs799917 and 33.20% CC, 46.88% CA, and 19.92% AA for rs2231142. A total of 825 human whole blood samples were examined for HPV infection by PCR, and the pooled DNA was tested for HPV infection using metagenomic sequencing. No HPV infections were detected among all 825 samples or the pooled blood samples. The incidence of breast cancer among the tested samples was estimated based on acceptable breast cancer risk factors and demographic data and was 1.47%. The present study provided data on SNPs and CNVs in breast cancer-related genes. The associations between SNPs rs2231142 and rs799917 and breast cancer should be further investigated in a case-control study since heterozygous and homozygous variants are more common. Based on the detection of HPV infection in the blood samples, HPV may not be associated with breast cancer, at least in the Northern Thai population.

Human papillomavirus and Merkel cell polyomavirus in Korean patients with nonsmall cell lung cancer: Evaluation and genetic variability of the noncoding control region.

Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT-ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor-associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases.

Clinical and statistical characteristics of patients with infertility on the background of chronic pelvic inflammatory diseases of the genital organs

Reproductive health and the formation of an adequate attitude to motherhood depend significantly on the social status of a woman. An increased number of people of fertile age with burdened somatic and obstetric and gynecological pathologies, a long-term stress load caused by the social and economic crisis and military actions in the country, a high specific weight of obstetric and perinatal complications - all these factors lead to a rapid decrease in the birth rate.Pathological changes in the hormonal status of female patients, sexual health disorders, and the progressive spread of inflammatory diseases of the reproductive system lead to an increased frequency of infertility. The etiological factor is most often a microbial association, which can be represented by both absolute pathogens with a predominantly sexual transmission route, and endogenous anaerobes and aerobes.Microbial associations contribute to better adaptation of the causative agent and its parasitism, increase the pathogenicity of each causative agent, their resistance to the antibiotics, which complicates the treatment of the disease as a whole. The prevalence of papillomavirus, herpes, cytomegalovirus infection in the structure of sexually transmitted inflammatory diseases negatively affects reproductive function.The objective: to analyze the risk factors for infertility in patients with inflammatory diseases of the genital organs which are determined by urogenital mixed infection.Materials and methods. A comprehensive clinical and laboratory examination of 154 married couples with infertility was carried out. The main group included 92 women who were examined for infertility and had chronic pelvic inflammatory disease (PID) caused by urogenital mixed infection.Depending on the detected pathogens, the women of the main group were divided into groups. During the In Pouch™ test in 30 (32.6%) patients who were included in the I observation group, Trichomonas vaginalis was found in biomaterial from the vagina in association with other conditionally pathogenic factors.Chlamydia trachomatis was diagnosed in polycomponent associations with other opportunistic flora in 34 (37.0%) women using polymerase chain reaction (PCR) in scrapings from the cervical canal - the II observation group.In 28 (30.4%) examined women, the human papillomavirus (HPV) was identified in the biological material from the cervix by PCR in Real time. Women with papillomavirus infection associated with opportunistic flora were included in the III observation group.To evaluate the results of the cytological examination, the Papanicolaou classification (CIN classification) and the Bethesda terminological system (The Bethesda system, TBS, 2014) were used.Results. As a result of a complex clinical and laboratory examination of women of reproductive age from 154 married couples who were observed for infertility, 60% (92 cases) of patients were diagnosed with PID due to urogenital mixed infection.Among the specific etiological factors, Trichomonas vaginalis was found in 32.6% (30 cases), Chlamydia trachomatis in 37.0% (34 cases), and HPV in 30.4% (28 cases) in multicomponent associations with representatives of opportunistic flora. It was established that, in addition to pathogenic agents of sexually transmitted infections, representatives of opportunistic flora negatively affect the reproductive function of women, among which the leading positions are occupied by mollicutes (Mycoplasma hominis, Ureaplasma urealyticum) - 67.4%; Enterococcus faecalis – 44.6%; Esherichia coli – 38.0%; Gardnerella vaginalis – 26.0%, with a maximum decrease in the vaginal content of the number or even absence of Lactobacillus spp.In the majority of women - 78.0% (64 cases), the inflammatory process had no pronounced clinical signs, in 22.0% it was almost asymptomatic, but was accompanied by frequent (up to 3-6 per year) relapses. Among the examined women of the III group, an association of two highly oncogenic HPV genotypes was found - 11 (39.5%) cases, three or more - 7 (25.0%) cases.A tendency to an earlier onset of sexual life was determined in women with sexually transmitted diseases, especially in the group with papillomavirus infection. Risk factors for infertility include the pathological course of childbirth and the postpartum period, surgical interventions, and infectious diseases. Among the diseases of the hepatic and biliary system, chronic cholecystitis prevailed.Conclusions. On the basis of the anamnestic assessment of reproductive health in the examined women with infertility on the background of chronic PID, it is possible to single out the most important factors that negatively affect the realization of the reproductive function: the age of a woman is less than 20 and more than 30 years, social maladaptation, working conditions and harmful habits, in particular smoking, as one of the cofactors of HPV-associated diseases of the cervix, as well as early sexual debut (up to 16 years), promiscuity, ignoring barrier contraception.In the genesis of pathological changes occurring in the urogenital tract, there are mixed infections, which potentially complicates diagnosis and negatively affects the results of treatment of associated forms of diseases.

The possibilities of predicting the individual risk of cervical cancer in women of reproductive age using mathematical modeling

Background. Cervical cancer (CC) refers to cancer of visual localization and in women of reproductive age remains one of the most common oncological diseases. The carcinogenesis of CC is caused by the persistence of highly oncogenic types of human papillomavirus (HPV), the level of carcinogenicity of which is the highest based on the criteria of the International Agency for Research on Cancer. However, cervical carcinogenesis does not occur in all cases of persistence of highly oncogenic types of HPV. This, in turn, determines the need for a thorough search, study and analysis of possible cofactors that can lead to neoplastic changes in the cervix.Aim. To develop a model for predicting the individual risk of CC in women of reproductive age, taking into account clinical, anamnestic, laboratory and histological data.Materials and methods. The material for the study was retrospective examination data from 251 patients of reproductive age who were treated at the Center for Gynecology and Reproductive Technologies of the National Medical Research Center “Medical and Rehabilitation Center”, Ministry of Health of Russia in the period 2015–2022. Results. Highly oncogenic HPV types were significantly more common in the group of patients with verified СС who took combined oral contraceptives (COC), compared with patients who did not take COC (p = 0.035). Multifactorial analysis allowed us to determine that long-term use of СОС for a total of more than 7 years is associated with a tendency to increase the risk of developing СС (hazard ratio 1.68; 95 % confidence interval 1.1–2.5; p = 0.010). According to the results of statistical calculation, the values of regression coefficients were obtained and the tendency to increase the risk of developing CC was predicted in the presence of such factors as: HPV type 16 persistence, body mass index, and the duration of COC intake in years.Conclusion. Thus, taking into account all possible risk factors for CC, the negative effect of cofactors, namely increased body mass index and prolonged intake of COC, on the course of HPV as the leading etiological factor of breast cancer, will allow us to identify groups at increased risk of developing CC, form an individual algorithm for monitoring and examination throughout the entire period of taking COC, as well as conduct individual cancer prevention by limiting the duration of taking COC.

Genome composition-based deep learning predicts oncogenic potential of HPVs.

Human papillomaviruses (HPVs) account for more than 30% of cancer cases, with definite identification of the oncogenic role of viral E6 and E7 genes. However, the identification of high-risk HPV genotypes has largely relied on lagged biological exploration and clinical observation, with types unclassified and oncogenicity unknown for many HPVs. In the present study, we retrieved and cleaned HPV sequence records with high quality and analyzed their genomic compositional traits of dinucleotide (DNT) and DNT representation (DCR) to overview the distribution difference among various types of HPVs. Then, a deep learning model was built to predict the oncogenic potential of all HPVs based on E6 and E7 genes. Our results showed that the main three groups of Alpha, Beta, and Gamma HPVs were clearly separated between/among types in the DCR trait for either E6 or E7 coding sequence (CDS) and were clustered within the same group. Moreover, the DCR data of either E6 or E7 were learnable with a convolutional neural network (CNN) model. Either CNN classifier predicted accurately the oncogenicity label of high and low oncogenic HPVs. In summary, the compositional traits of HPV oncogenicity-related genes E6 and E7 were much different between the high and low oncogenic HPVs, and the compositional trait of the DCR-based deep learning classifier predicted the oncogenic phenotype accurately of HPVs. The trained predictor in this study will facilitate the identification of HPV oncogenicity, particularly for those HPVs without clear genotype or phenotype.

Functional Characterisation of Surfactant Protein A as a Novel Prophylactic Means against Oncogenic HPV Infections.

Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant protein A (SP-A) as a novel molecule capable of recognising HPV16 pseudovirions (HPV16-PsVs) and reducing infection in a murine cervicovaginal HPV challenge model. Building on these findings, our current study aimed to assess SP-A's suitability as a broad-spectrum HPV-targeting molecule and its impact on innate immune responses. We demonstrate SP-A's ability to agglutinate and opsonise multiple oncogenic HPV-PsVs types, enhancing their uptake and clearance by RAW264.7 murine macrophages and THP-1 human-derived immune cells. The SP-A opsonisation of HPV not only led to increased lysosomal accumulation in macrophages and HaCaT keratinocytes but also resulted in a decreased infection of HaCaT cells, which was further decreased when co-cultured with innate immune cells. An analysis of human innate immune cell cytokine profiles revealed a significant inflammatory response upon SP-A exposure, potentially contributing to the overall inhibition of HPV infection. These results highlight the multi-layered impact of SP-A on HPV, innate immune cells and keratinocytes and lay the basis for the development of alternative prophylactic interventions against diverse HPV types.

Commensal HPVs Have Evolved to Be More Immunogenic Compared with High-Risk α-HPVs.

Commensal human papillomaviruses (HPVs) are responsible for persistent asymptomatic infection in the human population by maintaining low levels of the episomal genome in the stratified epithelia. Herein, we examined the immunogenicity of cutaneotropic HPVs that are commonly found in the skin. Using an in silico platform to determine human leukocyte antigen (HLA)-peptide complex binding affinity, we observed that early genes of cutaneotropic HPV types within the same species can generate multiple conserved, homologous peptides that bind with high affinity to HLA class I alleles. Interestingly, we discovered that commensal β, γ, μ, and ν HPVs contain significantly more immunogenic peptides compared with α-HPVs, which include high-risk, oncogenic HPV types. Our findings indicate that commensal HPV proteins have evolved to generate peptides that better complement their host's HLA repertoire. Promoting higher control by host T cell immunity in this way could be a mechanism by which HPVs achieve widespread asymptomatic colonization in humans. This work supports the role of commensal HPVs as immunogenic targets within epithelial cells, which may contribute to the immune regulation of the skin and mucosa.

Copy Number Profiling Implicates Thin High-Grade Squamous Intraepithelial Lesions as a True Precursor of Cervical Human Papillomavirus-Induced Squamous Cell Cancer

Full-thickness high-grade squamous intraepithelial lesions (HSIL) are precursors of invasive cervical squamous cell carcinoma (SCC). The World Health Organization and Lower Anogenital Squamous Terminology Standardization Project for human papilloma virus (HPV)–associated lesions divide full-thickness HSIL of the cervix into thin HSIL with thickness of 1 to 9 cell layers and the typical full-thickness HSIL of >10 cell layers. Although HPV oncogene transcripts and p16ink4a overexpression, as markers of transforming HPV infection, are detectable in thin HSIL, the biological significance of thin HSIL in cervical carcinogenesis remains poorly understood. To further characterize thin HSIL, we performed a comparative study of chromosomal copy number variations (CNV), an analysis of dysregulated genes present in the segments with CNV, and a generalized genetic complexity calculation for 31 thin HSIL, 31 thick HSIL, 24 microinvasive SCC (pT1a SCC), and 22 highly invasive SCC samples. Thin HSIL share various CNV and specific dysregulated gene pathways with thick HSIL and invasive SCC. Thin HSIL exhibited an average CNV of 11.6% compared with 14.1% for thick HSIL, 15.5% for pT1a SCC, and 26.6% for highly invasive SCC. The CNV included gains at 1q and 3q (40% and 43%, respectively), partial loss of 3p, and loss of chromosomes 11 (18%), 16 (50%), 20 (35%), and 22 (40%). Pathways affected solely in thin HSIL were those enhancing immune evasion and primarily involved the (interleukin) IL6, IL21, and IL23 genes. ILs are transiently upregulated in response to infection and play a crucial role in mounting antitumor T-cell activity. Deregulation reflects an attempt by the HPV to evade the initial immune response of the host. The primary pathways shared by thick HSIL and invasive SCC were interactions between lymphoid and nonlymphoid cells, NOTCH2 signaling, tight junction interactions (primarily of the claudin family), and FGR2 alternative splicing. Our results show that thin HSIL carry similar genetic changes as thick HSIL and SCC, indicating that thin HSIL are true precursor lesions that can progress to thick HSIL and SCC.

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.

The most common forms of cancer and oncogenic papillomaviruses

Breast, prostate, lung as well as colorectal carcinomas belong to leading positions in the world cancer incidence and mortality rankings. They make up about 40 % of newly diagnosed cancers. Connection of these cancers with oncogenic human papilloma viruses (HPVs) is being examined intensively, however it remains subject for discussion. Basing on case-control meta-analyses data were examined on oncogenic HPV detection in clinical samples of breast, prostate, lung and colorectal carcinomas. Findings on HPV genome activities were summarized. The results available prove to oncogenic HPVs as risk factors of the four enumerated above carcinomas.

MSphere of Influence: MmuPV1-a dual tropic papillomavirus, red herring, or novel insight into HPV pathogenesis.

James Romero-Masters works in the field of tumor virology, focusing on the role of the human papillomavirus oncogenes in pathogenesis. In this mSphere of Influence article, they reflect on how the article "Mouse papillomavirus infection persists in mucosal tissues of an immunocompetent mouse strain and progresses to cancer" impacted them, informing their research strategies, and what it means for the mouse papillomavirus model.

Vaccination with a Human Papillomavirus L2 Multimer Provides Broad Protection against 17 Human Papillomavirus Types in the Mouse Cervicovaginal Challenge Model.

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11-88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA's promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

The association between smoking and cervical human papillomavirus infection among women from indigenous communities in western Botswana

Introduction Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. Methods A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. Results A total of 171 participants with a median (interquartile range) age of 40 (31–50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. Conclusion These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.

Development of a human papillomavirus (HPV) multiplex immunoassay to profile HPV antibodies.

Neutralizing antibodies (NAbs) are considered the primary mechanism of vaccine-mediated protection against human papillomaviruses (HPV), the causative agent of cervical cancer. However, the minimum level of NAb needed for protection is currently unknown. The HPV pseudovirion-based neutralization assay (PBNA) is the gold standard method for assessing HPV antibody responses but is time-consuming and labor-intensive. With the development of higher valency HPV vaccines, alternative serological assays with the capacity for multiplexing would improve efficiency and output. Here we describe a multiplex bead-based immunoassay to characterize the antibody responses to the seven oncogenic HPV types (HPV16/18/31/33/45/52/58) contained in the current licensed nonavalent HPV vaccine. This assay can measure antibody isotypes and subclasses (total IgG, IgM, IgA1-2, IgG1-4), and can be adapted to measure other antibody features (e.g., Fc receptors) that contribute to vaccine immunity. When tested with serum samples from unvaccinated and vaccinated individuals, we found high concordance between HPV-specific IgG using this multiplex assay and NAbs measured with PBNA. Overall, this assay is high-throughput, sample-sparing, and time-saving, providing an alternative to existing assays for the measurement and characterization of HPV antibody responses.