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Human papillomavirus and cervical cancer in the microbial world: exploring the vaginal microecology.Frontiers in Cellular and Infection... 2024The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing.... (Review)
Review
The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing. However, its relationship with human papillomavirus (HPV) infection and cervical cancer is not yet clear. Therefore, this article provides a review of the association between the vaginal microbiota, HPV infection, and cervical cancer. We discuss the composition of the vaginal microbiota, its dysbiosis, and its relationship with HPV infection, as well as potential mechanisms in the development of cervical cancer. In addition, we assess the feasibility of treatment strategies such as probiotics and vaginal microbiota transplantation to modulate the vaginal microbiota for the prevention and treatment of diseases related to HPV infection and cervical cancer. In the future, extensive replication studies are still needed to gain a deeper understanding of the complex relationship between the vaginal microbiota, HPV infection, and cervical cancer, and to clarify the role of the vaginal microbiota as a potential biomarker for predicting disease outcomes, thus providing a theoretical basis for personalized testing.
Topics: Female; Humans; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Papillomavirus Infections; Papillomaviridae; Vagina; Biomarkers
PubMed: 38333037
DOI: 10.3389/fcimb.2024.1325500 -
Oncogene Sep 2023The incidence of human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly and has exceeded cervical cancer to become the most... (Review)
Review
The incidence of human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly and has exceeded cervical cancer to become the most common HPV-induced cancer in developed countries. Since patients with HPV + OPSCC respond very favorably to standard aggressive treatment, the emphasis has changed to reducing treatment intensity. However, recent multi-center clinical trials failed to show non-inferiority of de-escalation strategies on a population basis, highlighting the need to select low-risk patients likely to respond to de-intensified treatments. In contrast, there is a substantial proportion of patients who develop recurrent disease despite aggressive therapy. This supports that HPV + OPSCC is not a homogeneous disease, but comprises distinct subtypes with clinical and biological variations. The overall goal for this review is to identify biomarkers for HPV + OPSCC that may be relevant for patient stratification for personalized treatment. We discuss HPV + OPSCC as a heterogeneous disease from multifaceted perspectives including clinical behavior, tumor morphology, and molecular phenotype. Molecular profiling from bulk tumors as well as single-cell sequencing data are discussed as potential driving factors of heterogeneity between tumor subgroups. Finally, we evaluate key challenges that may impede in-depth investigations of HPV + OPSCC heterogeneity and outline potential future directions, including a section on racial and ethnic differences.
Topics: Humans; Carcinoma, Squamous Cell; Papillomavirus Infections; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Papillomaviridae
PubMed: 37666939
DOI: 10.1038/s41388-023-02819-y -
Human Vaccines & Immunotherapeutics Dec 2023As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18... (Randomized Controlled Trial)
Randomized Controlled Trial
As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly ( < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.
Topics: Adolescent; Adult; Child; Female; Humans; Middle Aged; Young Adult; Antibodies, Neutralizing; Antibodies, Viral; Double-Blind Method; East Asian People; Human papillomavirus 16; Human papillomavirus 18; Immunogenicity, Vaccine; Papillomavirus Infections; Papillomavirus Vaccines; Vaccines, Combined
PubMed: 37249310
DOI: 10.1080/21645515.2023.2209001 -
Veterinary Microbiology Feb 2024The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal... (Review)
Review
The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal health. Although more than 250 species have been described in humans, the total number of papillomaviruses (PVs) discovered in animals does not reach up to this number. In animals, PV infections are mostly asymptomatic or can cause variable clinical conditions ranging from self-limiting papillomas and other cutaneous and mucosal benign lesions to cancer. Most of animal PV types have been discovered in cattle, dogs, horses, and cats with other farm host species remaining overlooked. In particular, the number of PV types so far identified in sheep is limited. This paper comprehensively reviews ovine PVs features, including viral taxonomy and evolution; genome organization; viral tropism and pathogenesis; macroscopical features and histopathological patterns, as well as available diagnostics tools. Data are critically presented and discussed in terms of impact on veterinary and public health. The development of future dedicated research is also discussed.
Topics: Animals; Deltapapillomavirus; Papilloma; Papillomaviridae; Papillomavirus Infections; Sheep; Sheep Diseases; Virulence
PubMed: 38160507
DOI: 10.1016/j.vetmic.2023.109955 -
Nature Communications May 2024HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a...
HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a population-based trial of this strategy to reduce the incidence of HPV. All 89,547 women born 1994-1999 and resident in the capital region of Sweden were personally invited to concomitant HPV vaccination and HPV screening with 26,125 women (29.2%) enrolled between 2021-05-03 and 2022-12-31. Baseline HPV genotyping of cervical samples from the study participants finds, compared to pre-vaccination prevalences, a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, some decline for cross-protected HPV types but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicts that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 62-64% in 3 years. Baseline results are prevalences of HPV infection, validated transmission model projections, and power estimates for evaluating HPV incidence reductions at follow-up (+/-0.1% with 99.9% confidence). In conclusion, concomitant HPV vaccination and HPV screening appears to be a realistic option for faster cervical cancer elimination. Clinicaltrials.gov identifier: NCT04910802; EudraCT number: 2020-001169-34.
Topics: Humans; Female; Uterine Cervical Neoplasms; Papillomavirus Infections; Papillomavirus Vaccines; Adult; Sweden; Young Adult; Vaccination; Adolescent; Incidence; Mass Screening; Prevalence; Middle Aged; Early Detection of Cancer; Human papillomavirus 16; Human papillomavirus 18; Human Papillomavirus Viruses
PubMed: 38693149
DOI: 10.1038/s41467-024-47909-x -
International Journal of Clinical... Aug 2023Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These... (Review)
Review
Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These cancers claim > 400,000 lives annually. The persistent infection of HPV and the function of viral oncogenes are the primary causes of HPV-related cancers. However, only some HPV-infected persons or infected lesions will progress to cancer, and the burden of HPV-associated cancer varies widely according to gender and the part of the body infected. The dissimilarity in infection rates at different sites can explain only a small part of the differences observed. Much responsibility likely sits with contributions of specific epithelial cells and the cellular microenvironment at infected sites to the process of malignant transformation, both of which affect the regulation of viral gene expression and the viral life cycle. By understanding the biology of these epithelial sites, better diagnosis/treatment/management of HPV-associated cancer and/or pre-cancer lesions will be provided.
Topics: Male; Female; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Neoplasms; Carcinogenesis; Papillomaviridae; Uterine Cervical Neoplasms; Tumor Microenvironment
PubMed: 37199886
DOI: 10.1007/s10147-023-02340-y -
Journal of Infection and Public Health Oct 2023To assess the prevalence and characteristics of human papillomavirus (HPV) genotypes and its associated cervical lesions in Guangzhou, China, which may be useful for...
BACKGROUND
To assess the prevalence and characteristics of human papillomavirus (HPV) genotypes and its associated cervical lesions in Guangzhou, China, which may be useful for adjusting area-specific cervical cancer prevention and control strategies.
METHODS
A total of 58630 women were enrolled. Cervical specimens were collected for HPV DNA testing and/or cervical cytology. Patients with visible cervical lesions or abnormal screening results underwent further cervical biopsies.
RESULT
The overall HPV positive rate was 14.07%. The top five genotypes in Guangzhou were HPV 52 (3.06%), HPV 16 (2.28%), HPV 58 (1.80%), HPV 51 (1.32%), and HPV 39 (1.15%). The prevalence of overall HPV and vaccine-targeted HPV genotypes showed a significantly decreasing trend from 2016 to 2019 (P < 0.05). While, the infection rate of HPV 35 increased significantly during this time (P = 0.015). The age-specific prevalence of any HPV genotypes showed a bimodal curve, which peaked firstly among the < 20 y age group, and then peaked secondly among the > 59 y age group. Among HPV-positive women, the proportions of HSIL and cervical cancer increased significantly with age (P < 0.05). Among > 59 y age group, 9.35% HPV-positive cases were diagnosed as cervical cancer. HPV 16/18 was the most common cause of cervical cancer. While, the percentage of non-HPV 16/18 infection among cervical cancer patients increased over time, from 15.21% in 2015 to 26.32% in 2019 (P = 0.010). Besides that, the prevalence of non-HPV 16/18 genotypes among cervical cancer patients significantly increased with age, which peaked at the > 59 y age group (P = 0.014).
CONCLUSION
Although the prevalence of any HPV and vaccine-targeted HPV genotypes decreased significantly with time, it is still important to follow the HPV genotypes and their associated cancer risk after the large-scale popularization of HPV vaccine. And age should be taken into consideration in screening strategies and risk-based management of cervical cancer in Guangzhou.
Topics: Female; Humans; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia; Human Papillomavirus Viruses; Prevalence; China; Papillomaviridae; Genotype; Papillomavirus Infections
PubMed: 37562080
DOI: 10.1016/j.jiph.2023.07.013 -
Journal of Mathematical Biology Nov 2023Starting from a deterministic model, we propose and study a stochastic model for human papillomavirus infection and cervical cancer progression. Our analysis shows that...
Starting from a deterministic model, we propose and study a stochastic model for human papillomavirus infection and cervical cancer progression. Our analysis shows that the chronic infection state as random variables which have the ergodic invariant probability measure is necessary for progression from infected cell population to cervical cancer cells. It is shown that small progression rate from infected cells to precancerous cells and small microenvironmental noises associated with the progression rate and viral infection help to establish such chronic infection states. It implicates that large environmental noises associated with viral infection and the progression rate in vivo can reduce chronic infection. We further show that there will be a cervical cancer if the noise associated with precancerous cell growth is large enough. In addition, comparable numerical studies for the deterministic model and stochastic model, together with Hopf bifurcations in both deterministic and stochastic systems, highlight our analytical results.
Topics: Humans; Female; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Stochastic Processes; Persistent Infection; Virus Diseases; Precancerous Conditions
PubMed: 37951849
DOI: 10.1007/s00285-023-02018-z -
PLoS Medicine Oct 2023Cervical screening programs use testing for human papillomavirus (HPV) genotypes. Different HPV types differ greatly in prevalence and oncogenicity. We estimated the...
BACKGROUND
Cervical screening programs use testing for human papillomavirus (HPV) genotypes. Different HPV types differ greatly in prevalence and oncogenicity. We estimated the impact of cervical screening and follow-up for each HPV type.
METHODS AND FINDINGS
For each type of HPV, we calculated the number of women needed to screen (NNS) and number of women needing follow-up (NNF) to detect or prevent one cervical cancer case, using the following individual level input data (i) screening and cancer data for all women aged 25 to 80 years, resident in Sweden during 2004 to 2011 (N = 3,568,938); (ii) HPV type-specific prevalences and screening histories among women with cervical cancer in Sweden in 2002 to 2011(N = 4,254); (iii) HPV 16/18/other HPV prevalences in the population-based HPV screening program (N = 656,607); and (iv) exact HPV genotyping in a population-based cohort (n = 12,527). Historical screening attendance was associated with a 72% reduction of cervical cancer incidence caused by HPV16 (71.6%, 95% confidence interval (CI) [69.1%, 73.9%]) and a 54% reduction of cancer caused by HPV18 (53.8%, 95% CI [40.6%, 63.1%]). One case of HPV16-caused cervical cancer could be prevented for every 5,527 women attending screening (number needed to screen, NNS). Prevention of one case of HPV16-caused cervical cancer required follow-up of 147 HPV16-positive women (number needed to follow-up, NNF). The NNS and NNF were up to 40 to 500 times higher for HPV types commonly screened for with lower oncogenic potential (HPV35,39,51,56,59,66,68). For women below 30 years of age, NNS and NNF for HPV16 were 4,747 and 289, respectively, but >220,000 and >16,000 for HPV35,39,51,56,59,66,68. All estimates were either age-standarized or age-stratified. The primary limitation of our study is that NNS is dependent on the HPV prevalence that can differ between populations and over time. However, it can readily be recalculated in other settings and monitored when HPV type-specific prevalence changes. Other limitations include that in some age groups, there was little data and extrapolations had to be made. Finally, there were very few cervical cancer cases associated with certain HPV types in young age group.
CONCLUSIONS
In this study, we observed that the impact of cervical cancer screening varies depending on the HPV type screened for. Estimating and monitoring the impact of screening by HPV type can facilitate the design of effective and efficient HPV-based cervical screening programs.
TRIAL REGISTRATION
ClinicalTrials.gov with numbers NCT00479375, NCT01511328.
Topics: Female; Humans; Uterine Cervical Neoplasms; Early Detection of Cancer; Human Papillomavirus Viruses; Human papillomavirus 16; Papillomavirus Infections; Human papillomavirus 18; Papillomaviridae; Genotype
PubMed: 37889928
DOI: 10.1371/journal.pmed.1004304 -
The Journal of Veterinary Medical... Nov 2023Merkel cell carcinoma (MCC) is a rare skin tumor that shares a similar immunophenotype with Merkel cells, although its origin is debatable. More than 80% of human MCC... (Review)
Review
Merkel cell carcinoma (MCC) is a rare skin tumor that shares a similar immunophenotype with Merkel cells, although its origin is debatable. More than 80% of human MCC cases are associated with Merkel cell polyomavirus infections and viral gene integration. Recent studies have shown that the clinical and pathological characteristics of feline MCC are comparable to those of human MCC, including its occurrence in aged individuals, aggressive behavior, histopathological findings, and the expression of Merkel cell markers. More than 90% of feline MCC are positive for the Felis catus papillomavirus type 2 (FcaPV2) gene. Molecular changes involved in papillomavirus-associated tumorigenesis, such as increased p16 and decreased retinoblastoma (Rb) and p53 protein levels, were observed in FcaPV2-positive MCC, but not in FcaPV2-negative MCC cases. These features were also confirmed in FcaPV2-positive and -negative MCC cell lines. The expression of papillomavirus E6 and E7 genes, responsible for p53 degradation and Rb inhibition, respectively, was detected in tumor cells by in situ hybridization. Whole genome sequencing revealed the integration of FcaPV2 DNA into the host feline genome. MCC cases often develop concurrent skin lesions, such as viral plaque and squamous cell carcinoma, which are also associated with papillomavirus infection. These findings suggest that FcaPV2 infection and integration of viral genes are involved in the development of MCC in cats. This review provides an overview of the comparative pathology of feline and human MCC caused by different viruses and discusses their cell of origin.
Topics: Humans; Cats; Animals; Carcinoma, Merkel Cell; Tumor Suppressor Protein p53; Papillomaviridae; Merkel Cells; Skin Neoplasms; Cat Diseases
PubMed: 37743525
DOI: 10.1292/jvms.23-0322