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1.
Hum Vaccin Immunother ; 20(1): 2343192, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38745409

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


Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , China/epidemiology , Prevalence , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/epidemiology , Papillomaviridae/genetics , Papillomaviridae/classification , Genotype , Vaginal Neoplasms/virology , Vaginal Neoplasms/epidemiology , Condylomata Acuminata/virology , Condylomata Acuminata/epidemiology
2.
Rev Gastroenterol Peru ; 44(1): 35-40, 2024.
Article Es | MEDLINE | ID: mdl-38734910

OBJECTIVE: To determine the prevalence and genotypic characteristics of anal papillomaviruses in HIV-positive men who have sex with men (MSM). MATERIALS AND METHODS: This is a prospective cross-sectional observational study of HIV-positive MSM at Almenara General Hospital between September 2017 and December 2018. HPV detection and typing was performed using a polymerase chain reaction technique that evaluated 21 genotypes stratified according to oncogenic risk into six low-risk and fifteen high-risk. RESULTS: we evaluated 214 HIV-positive MSM. The overall prevalence of anal infection by papillomavirus infection was 70% (150/214). 86% (129/150) were caused by high-risk genotypes, 79% (102/129) of them were affected by a two or more-papillomavirus genotype. The most frequent high-risk genotypes were HPV-16, 31% (46/150); HPV-52, 22% (33/150); HPV-33, 21% (31/150); HPV-58, 21% (31/150) and HPV-31, 20% (30/150). In addition, HPV-18 reached 7% (10/150). The most frequent low-risk genotypes were HPV-6, 30% (45/150) and HPV-11, 29% (44/150). CONCLUSIONS: Prevalence of anal papillomavirus infection in HIV-positive MSM is very high in the hospital investigated. Most of these infections occurs with high-risk oncogenic genotypes. Papillomavirus 16 was the most frequent high-risk genotype.


Anus Diseases , Genotype , Homosexuality, Male , Papillomavirus Infections , Humans , Male , Cross-Sectional Studies , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Prevalence , Adult , Prospective Studies , Homosexuality, Male/statistics & numerical data , Middle Aged , Anus Diseases/epidemiology , Anus Diseases/virology , Papillomaviridae/genetics , HIV Infections/epidemiology , HIV Infections/complications , Young Adult
3.
Pol J Pathol ; 75(1): 36-39, 2024.
Article En | MEDLINE | ID: mdl-38741427

This research paper evaluates the efficacy of co-testing in precluding cervical cancer, with a particular focus on distinguishable outcomes of the human papillomavirus (HPV) vs. cytology tests. A retrospective review of 5948 patients, who tested positive for high-risk HPV but showed negative cytologic findings, revealed that 15.006% tested positive in subsequent screenings. A comparative analysis of various commercial HPV tests highlighted the precision of mRNA-based HPV testing by Aptima (Hologic) in reducing the likelihood of false-negative cytology. The paper challenges the conviction that a negative cytology alone suffices advocating for a condensed testing interval in instances of positive HPV outcomes, thereby facilitating earlier intervention and optimal preventive care. These findings unveil an exigency for reconsidering preventive strategies based on test outcomes.


Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Retrospective Studies , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/complications , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/diagnosis , Adult , Middle Aged , Vaginal Smears , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Aged , Uterine Cervical Dysplasia/virology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/diagnosis , Early Detection of Cancer/methods , Human Papillomavirus Viruses , Cytology
4.
Cancer Biol Ther ; 25(1): 2350249, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38722731

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.


Head and Neck Neoplasms , Microbiota , Papillomavirus Infections , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Head and Neck Neoplasms/virology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/microbiology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/genetics , Female , Papillomavirus Infections/virology , Papillomavirus Infections/immunology , Papillomavirus Infections/complications , Male , Microbiota/genetics , Tumor Microenvironment/immunology , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/microbiology , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/mortality , Prognosis , Middle Aged , Papillomaviridae/genetics , Aged
5.
J Med Virol ; 96(5): e29674, 2024 May.
Article En | MEDLINE | ID: mdl-38757834

Human Papillomaviruses (HPV) are a diverse family of non-enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer frequently involving integration of the virus into the host genome, leading to sustained oncogene expression and loss of capsid and genome maintenance proteins. Microhomology-mediated double-strand break repair, a DNA double-stranded breaks repair pathway present in many organisms, was initially thought to be a backup but it's now seen as vital, especially in homologous recombination-deficient contexts. Increasing evidence has identified microhomology (MH) near HPV integration junctions, suggesting MH-mediated repair pathways drive integration. In this comprehensive review, we present a detailed summary of both the mechanisms underlying MH-mediated repair and the evidence for its involvement in HPV integration in cancer. Lastly, we highlight the involvement of these processes in the integration of other DNA viruses and the broader implications on virus lifecycles and host innate immune response.


Carcinogenesis , Papillomaviridae , Papillomavirus Infections , Humans , Papillomaviridae/pathogenicity , Papillomaviridae/genetics , Papillomaviridae/physiology , Papillomavirus Infections/virology , Papillomavirus Infections/complications , Virus Integration , DNA Repair , DNA Breaks, Double-Stranded , DNA, Viral/genetics
6.
New Microbiol ; 47(1): 88-97, 2024 May.
Article En | MEDLINE | ID: mdl-38700888

Human papilloma virus (HPV) is the most common sexually transmitted viral agent in the world and the most common cause of cervical cancer. HPV prevalence and genotype distribution vary by region and demographic data. In a province in the south of Turkey that constantly receives immigration, we aimed to determine the prevalence of high-risk HPV (HR-HPV) genotypes, evaluate the compatibility between cervical Pap smear cytology results patients and HR-HPVs, and make an up-to-date contribution to the elucidation of epidemiological data. In this single-centre study, a total of 12,641 women aged 18 and over were evaluated retrospectively from January 2019 to July 2022. HPV detection and genotyping were analysed by the PCR method. Bethesda scoring was used for Pap smear cytological evaluation. The overall prevalence of HR-HPV was 12.6% (12.7% in Turkish women, 11.2% in foreign women). Among the typed HPVs that were detected, HPV-16 (31%) was found first, followed by HPV-18 (8%). The prevalence of HR-HPV was higher in women with abnormal cytology (977/1762, 55.4%) than in women with normal cytology (620/10879, 5.7%) (p<0.001). Turkey doesn't yet have a national HPV immunisation program. We think that determining the specific regional frequency of other HR-HPVs separately will be useful in the follow-up of the natural course of the type-specific infection and in vaccine studies in the future.


Emigrants and Immigrants , Genotype , Papillomaviridae , Papillomavirus Infections , Humans , Female , Turkey/epidemiology , Adult , Papillomavirus Infections/virology , Papillomavirus Infections/epidemiology , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/classification , Middle Aged , Young Adult , Retrospective Studies , Adolescent , Cervix Uteri/virology , Cervix Uteri/pathology , Prevalence , Aged , Vaginal Smears , Papanicolaou Test , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/epidemiology , Human Papillomavirus Viruses
8.
J Med Virol ; 96(5): e29652, 2024 May.
Article En | MEDLINE | ID: mdl-38727029

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high-risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real-time sequencing (SMRT) and evaluated its performance against MY09-11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09-11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR-HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR-HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype.


Genotype , Genotyping Techniques , Papillomaviridae , Papillomavirus Infections , Humans , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Female , Genotyping Techniques/methods , Papillomaviridae/genetics , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Sensitivity and Specificity , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/diagnosis , Sequence Analysis, DNA/methods , Early Detection of Cancer/methods , Oncogene Proteins, Viral/genetics , DNA, Viral/genetics , High-Throughput Nucleotide Sequencing/methods
9.
J Int AIDS Soc ; 27(5): e26242, 2024 May.
Article En | MEDLINE | ID: mdl-38695517

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.


HIV Infections , Homosexuality, Male , Squamous Intraepithelial Lesions , Transgender Persons , Humans , Thailand/epidemiology , Male , Adult , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/complications , Prevalence , Transgender Persons/statistics & numerical data , Incidence , Female , Homosexuality, Male/statistics & numerical data , Squamous Intraepithelial Lesions/epidemiology , Squamous Intraepithelial Lesions/pathology , Young Adult , Anus Neoplasms/epidemiology , Papillomaviridae/isolation & purification , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Cohort Studies , Biopsy , Genotype , Anal Canal/pathology , Anal Canal/virology
10.
J Med Virol ; 96(4): e29571, 2024 Apr.
Article En | MEDLINE | ID: mdl-38563330

Persistent infection with high-risk human papillomavirus (HR-HPV) is a well-established risk factor to the development of cervical intraepithelial neoplasia (CIN), a condition that can progress to cervical cancer (CC) a major health problem worldwide. Recently, there has been growing interest in exploring alternative therapies utilizing natural products, among which is the algae species Laurencia johnstonii Setchell & Gardner, 1924 (L. johnstonii), proposed for the management of precancerous lesions. The aim of this work was to determine the effect of an organic extract from L. johnstonii (ELj) in early cervical lesions (CIN 1). These CIN 1 lesions were generated in a murine model expressing the HR-HPV16 E7 oncoprotein (K14E7HPV transgenic mice) with a single exogenous hormonal stimulus using 17ß-estradiol. The histopathological studies, the determination of cell proliferation and of the apoptotic levels in cervical tissue, showed that, seven doses of ELj (30 mg/kg weight per day diluted in a DMSO-saline solution [1:7]) lead to recovery the architecture of cervical epithelium. Accordingly, in the transgenic mice it was observed a statistically significant decrease of the PCNA expression levels, a marker of cell proliferation, and a statistically significant increase in the apoptosis levels using Caspase 3 as a marker. In addition, we determined the expression levels of the tumor suppressor miR-218 and the oncomiRNA miR-21. Interestingly, our results may suggest that ELj treatment tended to restore the normal expression of both miRNAs as compared with controls being more evident in the non-transgenic induced mice. Differences of p < 0.05 were considered statistically significant through the whole study. Based on these results, we propose that the use of ELj could be an alternative for the treatment of cervical early lesions.


Laurencia , MicroRNAs , Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Mice , Animals , Laurencia/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/drug therapy , Papillomavirus Infections/genetics , Uterine Cervical Neoplasms/pathology , MicroRNAs/genetics , Mice, Transgenic , Carcinogenesis , Papillomaviridae/genetics
11.
J Med Virol ; 96(4): e29604, 2024 Apr.
Article En | MEDLINE | ID: mdl-38606779

Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial. Participants of the CATCH study were selected for viral load testing if they had completed the first four study visits and tested positive for HPV42 or HPV51 in at least one of these visits. HPV42 and HPV51 were chosen as they were among the most abundant low- and high-risk types, respectively, in the study sample. We measured viral load with a type-specific real-time polymerase chain reaction. Results were displayed using summary statistics. Of 461 enrolled participants, 39 were included in the HPV42 analysis set and 56 in the HPV51 analysis set. The median time between visits 1 and 4 was 3.7 months. The viral load (copies/cell) of HPV42 ranged from <0.001 to 13 434.1, and that of HPV51 from <0.001 to 967.1. The net median change in HPV42 viral load over all four visits was -1.04 copies/cell in the carrageenan and -147 copies/cell in the placebo arm (Wilcoxon rank sum test, p = 0.26). There was no net median change in HPV51 viral load over all four visits in either arm (p = 0.45). The use of a carrageenan-based gel is unlikely to reduce the viral load of HPVs 42 or 51.


Alphapapillomavirus , Papillomavirus Infections , Sexually Transmitted Diseases , Uterine Cervical Neoplasms , Humans , Female , Papillomavirus Infections/prevention & control , Carrageenan , Viral Load , Human Papillomavirus Viruses , Cervix Uteri , Papillomaviridae/genetics , DNA, Viral/analysis
12.
Viruses ; 16(4)2024 03 25.
Article En | MEDLINE | ID: mdl-38675844

Chromosomal instability (CIN) and aneuploidy are hallmarks of cancer. CIN is defined as a continuous rate of chromosome missegregation events over the course of multiple cell divisions. CIN causes aneuploidy, a state of abnormal chromosome content differing from a multiple of the haploid. Human papillomavirus (HPV) is a well-known cause of squamous cancers of the oropharynx, cervix, and anus. The HPV E6 and E7 oncogenes have well-known roles in carcinogenesis, but additional genomic events, such as CIN and aneuploidy, are often required for tumor formation. HPV+ squamous cancers have an increased frequency of specific types of CIN, including polar chromosomes. CIN leads to chromosome gains and losses (aneuploidies) specific to HPV+ cancers, which are distinct from HPV- cancers. HPV-specific CIN and aneuploidy may have implications for prognosis and therapeutic response and may provide insight into novel therapeutic vulnerabilities. Here, we review HPV-specific types of CIN and patterns of aneuploidy in squamous cancers, as well as how this impacts patient prognosis and treatment.


Aneuploidy , Chromosomal Instability , Papillomavirus Infections , Humans , Papillomavirus Infections/virology , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/genetics , Neoplasms, Squamous Cell/virology , Neoplasms, Squamous Cell/genetics , Neoplasms, Squamous Cell/pathology , Female , Alphapapillomavirus/genetics , Alphapapillomavirus/pathogenicity , Human Papillomavirus Viruses
13.
Viruses ; 16(4)2024 03 29.
Article En | MEDLINE | ID: mdl-38675879

Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application.


Biomarkers, Tumor , Head and Neck Neoplasms , Papillomavirus Infections , Precision Medicine , Squamous Cell Carcinoma of Head and Neck , Humans , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/therapy , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/virology , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/therapy , Precision Medicine/methods , Neoplasm Recurrence, Local/virology , Papillomaviridae/genetics , Papillomaviridae/classification
14.
Crit Rev Oncol Hematol ; 197: 104346, 2024 May.
Article En | MEDLINE | ID: mdl-38608913

Cervical cancer (CaCx) ranks as the fourth most prevalent cancer among women globally. Persistent infection of high-risk human papillomaviruses (HR-HPVs) is major etiological factor associated with CaCx. Signal Transducer and Activator of Transcription 3 (STAT3), a prominent member of the STAT family, has emerged as independent oncogenic driver. It is a target of many oncogenic viruses including HPV. How STAT3 influences HPV viral gene expression or gets affected by HPV is an area of active investigation. A better understanding of host-virus interaction will provide a prognostic and therapeutic window for CaCx control and management. In this comprehensive review, we delve into carcinogenic role of STAT3 in development of HPV-induced CaCx. With an emphasis on fascinating interplay between STAT3 and HPV genome, the review explores the diverse array of opportunities and challenges associated with this field to harness the prognostic and therapeutic potential of STAT3 in CaCx.


Papillomavirus Infections , STAT3 Transcription Factor , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/etiology , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/diagnosis , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Female , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Papillomavirus Infections/therapy , Prognosis , Carcinogenesis/genetics , Papillomaviridae/genetics
15.
JAMA Otolaryngol Head Neck Surg ; 150(5): 444-450, 2024 May 01.
Article En | MEDLINE | ID: mdl-38573644

Importance: The utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden is unknown. Objective: To determine if preoperative circulating tumor HPV DNA (ctHPVDNA) is associated with disease burden in patients with HPV+ OPSCC who have undergone transoral robotic surgery (TORS). Design, Setting, and Participants: This cross-sectional study comprised patients with HPV+ OPSCC who underwent primary TORS between September 2021 and April 2023 at one tertiary academic institution. Patients with treatment-naive HPV+ OPSCC (p16-positive) and preoperative ctHPVDNA levels were included, and those who underwent neck mass excision before ctHPVDNA collection were excluded. Main Outcomes and Measures: The main outcome was the association of increasing preoperative ctHPVDNA levels with tumor size and lymph node involvement in surgical pathology. The secondary outcome was the association between preoperative ctHPVDNA levels and adverse pathology, which included lymphovascular invasion, perineural invasion, or extranodal extension. Results: A total of 70 patients were included in the study (65 men [93%]; mean [SD] age, 61 [8] years). Baseline ctHPVDNA levels ranged from 0 fragments/milliliter of plasma (frag/mL) to 49 452 frag/mL (median [IQR], 272 [30-811] frag/mL). Overall, 58 patients (83%) had positive results for ctHPVDNA, 1 (1.4%) had indeterminate results, and 11 (15.6%) had negative results. The sensitivity of detectable ctHPVDNA for identifying patients with pathology-confirmed HPV+ OPSCC was 84%. Twenty-seven patients (39%) had pathologic tumor (pT) staging of pT0 or pT1, 34 (49%) had pT2 staging, and 9 patients (13%) had pT3 or pT4 staging. No clinically meaningful difference between detectable and undetectable preoperative ctHPVDNA cohorts was found for tumor size or adverse pathology. Although the median preoperative ctHPVDNA appeared to be higher in pT2 through pT4 stages and pN1 or pN2 stages, effect sizes were small (pT stage: η2, 0.002 [95% CI, -1.188 to 0.827]; pN stage: η2, 0.043 [95% CI, -0.188 to 2.600]). Median preoperative log(TTMV-HPV DNA) was higher in active smokers (8.79 [95% CI, 3.55-5.76]), compared with never smokers (5.92 [95% CI, -0.97 to 1.81]) and former smokers (4.99 [95% CI, 0.92-6.23]). Regression analysis did not show an association between tumor dimension or metastatic lymph node deposit size and preoperative log(TTMV-HPV DNA). After univariate analysis, no association was found between higher log(TTMV-HPV DNA) levels and adverse pathology. Conclusions and Relevance: In this cross-sectional study, preoperative ctHPVDNA levels were not associated with disease burden in patients with HPV+ OPSCC who underwent TORS.


DNA, Viral , Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , Male , Female , Cross-Sectional Studies , Oropharyngeal Neoplasms/virology , Oropharyngeal Neoplasms/surgery , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/blood , Middle Aged , DNA, Viral/analysis , DNA, Viral/blood , Papillomavirus Infections/virology , Papillomavirus Infections/blood , Papillomavirus Infections/complications , Aged , Robotic Surgical Procedures , Circulating Tumor DNA/blood , Preoperative Period , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/blood , Squamous Cell Carcinoma of Head and Neck/surgery , Squamous Cell Carcinoma of Head and Neck/pathology , Tumor Burden , Papillomaviridae/genetics
16.
JCO Glob Oncol ; 10: e2300408, 2024 Apr.
Article En | MEDLINE | ID: mdl-38662971

PURPOSE: Human papillomavirus (HPV) is widely recognized as a key contributing factor in cervical and oropharyngeal cancers. However, there has been limited research on the prevalence of concurrent HPV infections in various anatomic regions. This study aimed to investigate the prevalence and specific types of high-risk HPV (HR-HPV) infections in the cervical and oral regions of females in Punjab, Pakistan. METHODS: We conducted a cross-sectional study involving women seeking care for general gynecologic issues at the gynecologic Outpatient Department of Lady Wallington Hospital in Lahore. After interviews and clinical examinations, we collected whole-saliva samples and high vaginal swabs from each participant. HR-HPV detection and genotyping were performed using real-time polymerase chain reaction at both the anatomic sites. RESULTS: In this study, 170 females, averaging 35.36 ± 8.305 years, participated. HR-HPV infection was more prevalent in the cervix (83/170 [48.8%]) than in the oral cavity (19/170 [11.2%]). Concordant HPV infections occurred in 10/170 participants (5.9%). HPV 16 was the most common genotype in cervical and oral locations, at rates of 21.8% and 5.3%, respectively, among concordant HR-HPV types. Socioeconomic status (P = .013), age at first sexual intercourse (P = .015), and history of oral sex (P = .01) were significantly associated with concurrent HR-HPV infection in both regions. CONCLUSION: This study suggests that HR-HPV cervical infections may increase the risk of oral transmission, especially during orogenital sexual practices. Thus, it is important to recognize that HPV infections may be linked in both areas. We emphasize the importance of comprehensive cervical and oral examinations and HPV vaccination in young women irrespective of their sexual practices.


Cervix Uteri , Papillomavirus Infections , Humans , Female , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Cross-Sectional Studies , Pakistan/epidemiology , Adult , Cervix Uteri/virology , Middle Aged , Mouth/virology , Prevalence , Young Adult , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Risk Factors , Genotype
17.
Clin Epigenetics ; 16(1): 56, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643219

BACKGROUND: Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. RESULTS: Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. CONCLUSIONS: This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.


Carcinoma, Squamous Cell , Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Developing Countries , Papillomavirus Infections/diagnosis , Papillomavirus Infections/genetics , Genetic Markers , DNA Methylation , Carcinoma, Squamous Cell/genetics , Papillomaviridae/genetics , Vaginal Smears/methods , Tumor Suppressor Proteins/genetics
18.
Hum Vaccin Immunother ; 20(1): 2337161, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38566539

The epidemiological and clinical aspects of Human Papillomavirus (HPV) infection in women have been extensively studied. However, there is a lack of information regarding HPV characteristics in males. In this study, we conducted a retrospective and observational study of 3737 consecutive male individuals attending outpatient clinics of Guangdong Women and Children Hospital from 2012 to 2023 in Guangzhou, South China, to determine the age- and genotype-specific prevalence of HPV in men. The results showed the overall prevalence of HPV among men was 42.15% (1575/3737), with variations ranging from 29.55% to 81.31% across distinct diagnostic populations. Low-risk HPV6 (15.47%), HPV11 (8.94%), and high-risk HPV52 (5.51%) were the most common types. The annual HPV prevalence decreased significantly (Z = -3.882, p < .001), ranging from 31.44% to 52.90%. 28.77% (1075/3737) of men manifested infection with a singular HPV type, predominantly identified as a low-risk type. The age-specific distribution of HPV infections revealed distinctive peaks in the < 25 y age group (47.60%, 208/437) and the 40-44 y age group (44.51%, 154/346). Notably, the positive rate of Chlamydia trachomatis was significantly higher among HPV-positive individuals in comparison to HPV-negatives (16.14% vs. 11.25%, p < .05). Our findings reveal a substantial prevalence of HPV infection among outpatient men in Guangzhou, South China. It is recommended to consider the inclusion of HPV vaccination for adolescent males in national immunization schedules, once an adequate supply of vaccines is accessible.


Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Male , China/epidemiology , Genotype , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Prevalence , Retrospective Studies , Risk , Uterine Cervical Neoplasms/prevention & control , Vaccination , Young Adult , Adult
19.
Sci Rep ; 14(1): 7976, 2024 04 04.
Article En | MEDLINE | ID: mdl-38575600

Cervical cancer is a significant public health concern in Ethiopia. It is mainly caused by persistent infection with the human papillomaviruses. The aim of this study was to assess the relationship between carcinogenic risk of probable, possible and low risk HPV infection and those of cervical intraepithelial neoplasia (CIN) and cervical cancer. A cross sectional study nested from prospective cohort study was conducted in Bahir Dar, northwest Ethiopia. Statistical analyses were performed using SPSSversion 26.0. HPV-16 was associated with a relatively higher risk of CIN II+, (AOR = 15.42; 95% CI 6.81-34.91). In addition, HPV-52, -18, -53 and -58, were significantly associated with an increased risk of CIN II+, (AOR = 7.38 (1.73-31.54), 5.42 (1.61-18.31), 4.08 (1.53-10.87), and 3.17 (1.00-10.03)), respectively. The current study shows high rate of HPV with predominance of HPV-16, -53, -58, -18, -35, and -52. The quadrivalent and nonavalent vaccine had only covered 27.1% and 45% of the circulating HPV genotypes. Ethiopia may need to consider introduction of nonavalent vaccine into the national public health strategy. Polyvalent vaccine which includes the genotypes not covered by existing approved vaccines should be considered.


Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Human Papillomavirus Viruses , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Cross-Sectional Studies , Prospective Studies , Papillomaviridae/genetics , Human papillomavirus 16 , Genotype , Vaccines, Combined
20.
Rev Med Virol ; 34(3): e2537, 2024 May.
Article En | MEDLINE | ID: mdl-38666757

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.


Neoplasms , Papillomavirus Infections , Humans , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Papillomavirus Infections/prevention & control , Papillomavirus Infections/transmission , Neoplasms/virology , Neoplasms/epidemiology , Neoplasms/prevention & control , Papillomaviridae/physiology , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/immunology , Host Microbial Interactions , Female , Male
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