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Results for “Human papillomavirus 18”

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PubMed2025

Oncoproteins E6/E7 of the human papillomavirus types 16 & 18 synergize in modulating oncogenes and tumor suppressor proteins in colorectal cancer.

OBJECTIVE: Our study presents a novel analysis of the oncogenes and tumor suppressor proteins directly modulated by E6/E7 of high-risk HPV types 16 and 18, in colorectal cancer (CRC). METHODS: HCT 116 (KRAS mutant) & HT-29 (TP53 mutant) cell models of CRC were transduced with E6/E7 of HPV16 and HPV18, individually and in combination. Further, we utilized a liquid chromatography mass spectrometry (LC-MS/MS) approach to analyze and compare the proteomes of both CRC cell models. RESULTS: We generated six stably transduced cell lines. Our data revealed a significantly higher, HPV-induced modulation of oncogenes and tumor suppressor proteins in the TP53 mutant model, as compared to the KRAS mutant model (p ≤ 0.01). Less than 1% of the genes were commonly modulated by HPV, between both models. We also report that HT-29 cells, expressing E6/E7 of both HPV types, significantly reduced the suppression of oncogenes as compared to cells expressing E6/E7 of either HPV types individually (p-value ≤0.00001). CONCLUSION: Our data imply that HPV coinfections leads to the sustenance of a pro-oncogenic environment in CRC. HPV modulates different oncogenes/tumor suppressor proteins in CRC of varying mutational backgrounds, thus highlighting the importance of personalized therapies for such diseases with mutational heterogeneity.

Humans↗

PubMed2025

Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions.

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors. We have previously shown that HPV18 recruits the host protein CTCF to viral episomes to control the differentiation-dependent viral transcriptional programme. Since CTCF is an important regulator of host cell transcription via coordination of epigenetic boundaries and long-range chromosomal interactions, we hypothesised that HPV18 may also manipulate CTCF to contribute to host transcription reprogramming. Analysis of CTCF binding in the host cell genome by ChIP-Seq revealed that while the total number of CTCF binding sites is not altered by the virus, there are a sub-set of CTCF binding sites that are either enriched or depleted of CTCF. Many of these altered sites are clustered within regulatory elements of differentially expressed genes, including the tumour suppressor gene cell adhesion molecule 1 (CADM1), which supresses epithelial cell growth and invasion. We show that HPV18 establishment results in reduced CTCF binding at the CADM1 promoter and upstream enhancer. Loss of CTCF binding is coincident with epigenetic repression of CADM1, in the absence of CpG hypermethylation, while adjacent genes including the transcriptional regulator ZBTB16 are activated. These data indicate that the CADM1 locus is subject to topological rearrangement following HPV18 establishment. We tested this hypothesis using 4C-Seq (circular chromosome confirmation capture-sequencing) and show that HPV18 establishment causes a loss of long-range chromosomal interactions between the CADM1 transcriptional start site and the upstream transcriptional enhancer. These data show that HPV18 manipulates host cell promoter-enhancer interactions to drive transcriptional reprogramming that may contribute to HPV-induced disease progression.

Humans↗

PubMed2026

Prevalence and persistence of high-risk HPV genotypes in unvaccinated asymptomatic women: a six-year study in Peru.

OBJECTIVE: This study was to determine the frequency of HPV-hr and describe the distribution by categories (HPV16, HPV18, HPV-hr non16/18) among unvaccinated asymptomatic women in Peru over a 6-year period (2013-2018). In addition, the disease clearance rate is assessed in a percentage of cases. RESULTS: Of the 6,665 samples, 2,240 (33.6%) tested positive for HPV. Among the positive cases, single-genotype infections were caused by HPV-16 (14.8%), followed by HPV-18 (2.2%) and clustered high-risk HPV (HR-HPV) genotypes (66.7%). Multiple HPV-16 infections were more common than HPV-18 infections. In addition, 22 cases (1%) presented with infection with HPV-16, HPV-18, and HR-HPV genotypes. A subset of 116 samples from patients with 1 to 2 years of follow-up was analyzed further. Clearance rates were high, at 68.8% for HPV-16 infections and 67.5% for HR-HPV infections. However, the elimination rate of multiple infections with HPV-16 and HR-HPV genotypes was slightly lower, at 55.6%.

Prevalence↗

PubMed2025

Genome-Wide Association Analyses of HPV16 and HPV18 Seropositivity Identify Susceptibility Loci for Cervical Cancer.

Infection by high-risk human papillomavirus is known to exacerbate cervical cancer development. The host immune response is crucial in disease regression. Large-scale genetic association studies for cervical cancer have identified few susceptibility variants, mainly at the human leukocyte antigen locus on chromosome 6. We hypothesized that the host immune response modifies cervical cancer risk and performed three genome-wide association analyses for HPV16, HPV18 and HPV16/18 seropositivity in 7814, 7924, and 7924 samples from the UK Biobank, followed by validation genotyping in the German Cervigen case-control series of cervical cancer and dysplasia. In GWAS analyses, we identified two loci associated with HPV16 seropositivity (6p21.32 and 15q26.2), two loci associated with HPV18 seropositivity (5q31.2 and 14q24.3), and one locus for HPV16 and/or HPV18 seropositivity (at 6p21.32). MAGMA gene-based analysis identified HLA-DQA1 and HLA-DQB1 as genome-wide significant (GWS) genes. In validation genotyping, the genome-wide significant lead variant at 6p21.32, rs9272293 associated with overall cervical disease (OR = 0.86, p = 0.004, 95% CI = 0.78-0.95, n = 3710) and HPV16 positive invasive cancer (OR = 0.73, p = 0.005, 95% CI = 0.59-0.91, n = 1431). This variant was found to be a robust eQTL for HLA-DRB1, HLA-DQB1-AS1, C4B, HLA-DRB5, HLA-DRB6, HLA-DQB1, and HLA-DPB1 in a series of cervical epithelial tissue samples. We additionally genotyped twenty-four HPV seropositivity variants below the GWS threshold out of which eleven variants were found to be associated with cervical disease in our cohort, suggesting that further seropositivity variants may determine cervical disease outcome. Our study identifies novel genomic risk loci that associate with HPV type-specific cervical cancer and dysplasia risk and provides evidence for candidate genes at one of the risk loci.

Humans↗

PubMed2025

Analytical and clinical performance validation of HPV-SEQ, a novel NGS-based liquid biopsy platform for detection and quantification of human papilloma virus circulating tumor DNA.

BACKGROUND: Human papillomavirus (HPV) is the primary causative driver of oropharyngeal squamous cell carcinoma (OPSCC). Accurate detection of HPV-DNA is critical for risk stratification and management of OPSCC. However, assays designed to detect HPV in primary tumors do not allow monitoring of HPV-DNA over time, whereas commercially available droplet digital PCR-based methods for assessment of circulating cell free (cf)HPV-DNA in plasma remain suboptimal, hindering adaptation into clinical practice. We have developed HPV-SEQ, a novel next-generation-sequencing (NGS) based method for detection and quantification of HPV16/18 DNA in plasma of patients with OPSCC. METHODS: The assay uses primers targeting the L1 gene of HPV16 and HPV18 viral genomes and strain specific calibrators at a defined concentration to determine the ratio of native HPV to a known standard, enabling accurate reporting of patient-derived HPV16/18 viral load in a sample. This study was conducted using two different patient populations in addition to healthy donors and contrived material. All experiments were performed to fulfill several applicable analytical, performance and validation guidelines. RESULTS: A thorough analytical characterization and clinical validation of this platform demonstrates that HPV-SEQ detects cfHPV-DNA with exceptional limit of quantification and high precision, providing a foundation for integrating this platform into clinical settings. CONCLUSIONS: This ultra-sensitive HPV profiling method with optimal analytical performance may represent a significant advancement in risk stratification, treatment management, and post-treatment surveillance for patients with OPSCC.

Humans↗

PubMed2025

Clinicopathologic and Molecular Analysis of Colorectal Carcinomas With Spectrum of Neuroendocrine Carcinoma Components.

The genetics of colorectal carcinoma (CRC) with neuroendocrine differentiation remain poorly understood; recent studies focusing on pure neuroendocrine carcinomas (NECs) demonstrated mutation profiles closely resembling colorectal adenocarcinomas (ACAs) with more frequent BRAF mutations and Rb/p16 pathway dysregulation. However, pathogenesis of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) and ACAs with minor NEC component (AMiNECs) remains controversial. We aimed to define the behavior and molecular underpinnings of these tumors in comparison with conventional ACAs. In total, 20 NECs, 10 MiNENs, and 8 AMiNECs were compared with 100 controls with ACAs. Well-differentiated neuroendocrine tumors of any grade were excluded. CRCs with NEC components presented at a slightly earlier age (mean, 59 vs 65 years; P = .24) in a similar sex distribution (male:female, 1:1.11 vs 1.04:1; P = .97). The majority of cases arose either from a precursor adenoma (42%) or in the setting of inflammatory bowel disease (18%), whereas 5 of 10 cases (50%) originating from the rectum were human papillomavirus driven. Despite similarity in tumor size and depth of invasion among all groups, CRCs with NEC components showed more frequent lymph node and distant metastases (P < .001 each), leading to more advanced disease stage (stage III/IV; P < .001) and worse 5-year survival outcomes (35.4% for NECs, 30% for MiNENs, and 41.6% for AMiNECs vs 85.1% for ACAs; P < .001), compared with ACAs. Next-generation sequencing revealed more frequent BRAF (40% vs 3%; P < .001) and BRCA1 alterations (15% vs 1%; P = .001) in NECs compared with ACAs. Genomic alterations in RB1 were exclusively found in NECs (10%) and MiNENs (20%). In conclusion, the presence of any NEC component (from AMiNEC to pure NEC) in CRC carries a dismal prognosis. Yet, these tumors are more likely to harbor potentially targetable mutations such as BRAF p.V600E and alterations in BRCA1/2, which are of therapeutic value.

Humans↗

PubMed1978

The occurrence of human wart-virus antibodies in dogs, pigs and cattle.

Using the immunodiffusion method, antibodies against human wart-virus were detected in dog, pig and cattle sera but not in horse and reindeer sera. Antibodies were found in 25 percent (28/114) of the dog sera, the prevalence of antibodies being fairly similar to that in children of the same age. By electron microscopy the antibodies in dog sera were shown to attach to and precipitate the human wart-virus particles, and in immunodiffusion the precipitation lines of human and dog sera were shown to be identical. Of the cattle sera studied, 10 percent (10/97) and of the pig sera 13 percent (5/40) gave a faint precipitation line, having identity with that given by the human sera, against human wart-virus. Conversely 18 percent (9/50) of adult human sera contained precipitating antibodies against a bovine papilloma antigen, probably bovine papilloma virus.

Animals↗

PubMed2024

Analysis of human papillomavirus type 16 E4, E5 and L2 gene variations among women with cervical infection in Xinjiang, China.

BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

Humans↗

PubMed2026

A droplet digital PCR assay targeting 16 human papillomavirus genotypes.

Background. Cervical screening with high-precision assays such as human papillomavirus (HPV) DNA testing is essential for the detection and treatment of precancerous lesions. HPV genotypes have different oncogenic potential and require different clinical management, illustrating the importance of extended genotyping. HPV quantification has demonstrated clinical relevance in both diagnosis and treatment. Objective. To develop a droplet digital PCR assay for the detection and quantification of 16 HPV genotypes, with comparison to a commercial test and validation on clinical samples. Methods. Primers and probes were designed to target the E6 region of 16 HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73 and 82. Each target was evaluated to assess performance and reliability using synthetic DNA constructs, quantified international reference standards and clinical screening samples (n=303) genotyped using the Seegene Anyplex II HR HPV Detection assay. Results. Each assay demonstrated high target specificity, without cross-reactivity observed among the HPV genotypes selected. Using international molecular standards, the assay reliably detected high-risk genotypes across serial dilutions, with detection down to the level of one international unit or genome equivalent per microlitre. When applied to clinical samples with and without a histological diagnosis of cervical intraepithelial neoplasia 2 or worse (CIN2+), the assay reliably detected key HPV genotypes, with the exception of 7 of 234 (3%) of HPV-positive samples, all of which exhibited very low viral load. Conclusion. Although previous studies have described digital PCR methods targeting HPV E6, they have typically focused on a limited number of genotypes. This study expands upon existing methodology by introducing a sensitive and specific method for detection and quantification of 16 high-risk and potentially high-risk HPV genotypes.

PCR↗

PubMed2026

Systemic Comorbidities of Keloid and Hypertrophic Scars: A Phenome-Wide Association Study in a Multiethnic U.S. Pediatric Cohort.

BACKGROUND: Excessive scarring (ES), including keloids and hypertrophic scars, impairs function, appearance, and quality of life in children. Its pediatric comorbidity spectrum is not well defined, limiting anticipatory guidance and multidisciplinary care. This research aims to investigate comorbidities of ES in a diverse pediatric cohort using a phenome-wide association study (PheWAS). METHODS: This population-based study leveraged longitudinal electronic health record (EHR) data from participants enrolled in the Children's Hospital of Philadelphia (CHOP) from 2006. Diagnosis codes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] and Tenth Revision [ICD-10-CM]) were mapped to 3109 phenotype codes (PheCodes). PheWAS analyses were conducted using logistic regression, with Bonferroni correction applied to account for multiple testing. RESULTS: Among 86,092 pediatric participants, 662 (0.77%) were identified with ES; the remaining served as controls. Multivariable PheWAS screening identified 154 significant associations across 16 disease categories, of which 105 were not reported previously to our knowledge. Dermatologic phenotypes (n = 28; 18%) were most enriched, including acne and other follicular disorders, eczema, pigmentary changes, papulosquamous and granulomatous disorders, and cutaneous infections. Respiratory phenotypes (n = 21; 14%) included respiratory failure, pneumonia, asthma, allergic rhinitis, pharyngitis, and tonsillar hypertrophy. Sense organ disorders (n = 19; 12%) comprised conjunctivitis, refractive errors, otitis, and hearing impairment. Infection-related phenotypes (n = 14; 9%) highlighted susceptibility to viral (influenza, human papillomavirus [HPV], molluscum contagiosum), fungal (candidiasis, dermatophytosis), and bacterial infections. CONCLUSIONS: These findings suggest that ES in children indicates not only localized wound-healing impairment, but also systemic immune, developmental, and proliferative dysregulations, emphasizing the need for genetic and mechanistic studies to clarify causal pathways and multidisciplinary surveillance beyond dermatologic care.

Humans↗

PubMed2025

Human papillomavirus (HPV) genotypes extended prevalence in the female population from a city in Northern Chile.

BACKGROUND: Cervical cancer is primarily associated with the presence of human papillomavirus (HPV), with high-risk genotypes HPV-16 and HPV-18 being the focus of vaccination programs in developing countries such as Chile. Preventive screening for cervical cancer in women aged 25 to 64 years remains centered on cytological techniques and is primarily performed based on clinical suspicion of cervical lesions. However, extended screening for HPV genotypes using DNA amplification methods is not routinely applied to the Chilean female population yet. This study aimed to determine the prevalence of high- and low-risk HPV genotypes in women without known risk factors in a city in northern Chile. METHODS: Cervicovaginal brushing samples were obtained from 390 women from Antofagasta city, Northern Chile, aged between 25 and 64 years; genomic DNA was extracted, and multiplex real-time PCR analysis was used to identify a larger group of high- and low-risk HPV genotypes. RESULTS: Among 390 samples, HPV prevalence was 36.9%, of which 54.9% were high-risk genotypes, 18.7% were low-risk genotypes, and 26.4% showed mixed infection with both high- and low-risk genotypes. High-risk genotypes 16, 58, 39, and 31 were the most frequently identified among HPV-positive samples. Furthermore, a significant association was observed between HPV presence and both age and suspicion of cervical alteration, and women testing positive for other sexually transmitted infections (STIs) were more likely to acquire HPV. CONCLUSIONS: Implementing a screening program that incorporates extended HPV genotyping in Chile, including testing for high-risk genotypes 16, 18, 31, 39, and 58, is crucial to optimize control, early detection, and vaccination efforts for Chilean circulating HPV genotypes that are not covered by the actual vaccine, thus contributing to a more effective reduction in the burden of disease associated with the virus.

Humans↗