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Pediatrics Jul 2023A single dose of human papillomavirus (HPV) vaccine would simplify logistics and reduce costs of vaccination programs worldwide. We conducted a phase IIa trial to...
OBJECTIVES
A single dose of human papillomavirus (HPV) vaccine would simplify logistics and reduce costs of vaccination programs worldwide. We conducted a phase IIa trial to determine the stability of HPV type-specific antibody responses after a single dose of the nonavalent HPV vaccine, Gardasil9.
METHODS
Two hundred-and-one healthy 9 to 11-year-old girls and boys were enrolled at 2 centers in the United States to receive a prime dose of the nonavalent vaccine at baseline, a delayed dose at month 24, and an optional third dose at month 30. Blood samples were collected to measure HPV type-specific antibodies at baseline and at 6, 12, 18, 24, and 30 months after the prime dose. The primary outcomes were serum HPV16 and HPV18 antibody responses.
RESULTS
In both girls and boys, geometric mean concentrations of HPV16 and HPV18 antibodies increased at 6 months, declined between months 6 to 12, and then remained stable and high (at 20- and 10-times those at baseline for HPV16 and HPV18, respectively) throughout months 12, 18, and 24 (prebooster) visits. Both HPV16 and HPV18 antibody responses demonstrated anamnestic boosting effect at 30-months after the delayed (24-month) booster dose.
CONCLUSIONS
A single dose of the nonavalent HPV vaccine induced persistent and stable HPV16 and HPV18 antibody responses up to 24 months. This study contributes important immunogenicity data to inform feasibility of the single dose HPV vaccination paradigm. Further research is needed to assess the long-term antibody stability and individual clinical and public health benefit of the single dose schedule.
Topics: Male; Female; Humans; Child; Papillomavirus Vaccines; Human papillomavirus 16; Antibody Formation; Papillomavirus Infections; Human papillomavirus 18; Antibodies, Viral
PubMed: 37317810
DOI: 10.1542/peds.2022-060301 -
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 -
Journal of Obstetrics and Gynaecology :... Dec 2023High-risk (HR)-human papillomavirus (HPV) is the leading cause of precancerous cervical lesions in patients with chronic untreated infection. We investigated the...
High-risk (HR)-human papillomavirus (HPV) is the leading cause of precancerous cervical lesions in patients with chronic untreated infection. We investigated the relationships among several vaginal microbiological alterations, oncogene E6/E7 expression, and HR-HPV. A total of 1327 women who underwent HPV screening, vaginal microecology determination, and fluid-based thin-layer cytological test were enrolled and classified into the HPV-negative group, the low-risk (LR)-HPV-positive group, and the HR-HPV-positive group. The status of cervical HPV infection, vaginal microecology, and E6/E7 mRNA expression were examined sequentially. The effect of HR-HPV infection on cervical cancer (CC) was meticulously assessed, and associations between HR-HPV infection and vaginal microecology and E6/E7 mRNA were identified. In total 548/1327 patients were HPV positive, including LR-HPV infection ( = 132) and HR-HPV infection ( = 416). Patients in the HR-HPV positive group revealed higher detection rates of bacterial vaginosis (BV), trichomonal vaginitis (TV), and vulvovaginal candidiasis (VVC) relative to the HPV negative group. A higher E6/E7 mRNA expression was identified in HR-HPV patients compared to LR-HPV patients. BV and E6/E7 mRNA were classified as independent risk factors for HR-HPV infection. Patients with HR-HPV infection were more susceptible to CC development. Overall, BV and E6/E7 mRNA expression were identified as independent risk factors for HR-HPV infection.IMPACT STATEMENT Through literature review, we found that vaginal ecological changes increase the risk of HPV infection, and HPV persistent infection is an important risk factor for cervical precancerous lesions and cervical cancer. In addition, HPV gene E6/E7 is expressed in HPV-positive cervical cancer cells, which is related to cell malignant transformation and even tumorigenesis. This study further revealed that bacterial vaginosis (BV) and E6/E7 mRNA were independently correlated with HR-HPV infection, and HR-HPV infection increased the risk of cervical cancer. E6/E7 mRNA detection may be used as a new auxiliary diagnostic index for HR-HPV infection. In addition, this study provides a reference for whether the restoration of vaginal microecological balance in patients with BV undergoing clinical treatment is conducive to HR-HPV regression, and provides theoretical support for the prevention and control of cervical cancer microecological approach and the occurrence and development of cervical cancer.
Topics: Female; Humans; Human Papillomavirus Viruses; Oncogene Proteins, Viral; Oncogenes; Papillomaviridae; Papillomavirus Infections; RNA, Messenger; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginosis, Bacterial; Review Literature as Topic
PubMed: 36645341
DOI: 10.1080/01443615.2022.2161349 -
Clinical Microbiology and Infection :... Aug 2023Previous studies have suggested a protective effect of male circumcision on human papillomavirus (HPV) infections in males, and that this protection may be conferred to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous studies have suggested a protective effect of male circumcision on human papillomavirus (HPV) infections in males, and that this protection may be conferred to their female sexual partners.
OBJECTIVES
To synthesize the available evidence on the association between male circumcision and HPV infections in males and females.
DATA SOURCES
We searched MEDLINE, Embase, Scopus, Cochrane, LILACS, and ProQuest Dissertations & Theses Global for records published up to 22 June 2022.
STUDY ELIGIBILITY
We considered observational and experimental studies that assessed male circumcision status and HPV prevalence, incidence, or clearance in males or females for inclusion.
PARTICIPANTS
Males and their female sexual partners who were tested for genital HPV infection.
INTERVENTIONS
Male circumcision compared with no circumcision.
THE RISK-OF-BIAS ASSESSMENT
The Newcastle-Ottawa scale was used for observational studies, and the Cochrane risk-of-bias tool was used for randomized trials.
DATA SYNTHESIS
We estimated summary measures of effect and 95% CIs for the prevalence, incidence, and clearance of HPV infections in males and females using random-effects meta-analysis. We assessed the effect modification of circumcision on HPV prevalence by the penile site in males using random-effects meta-regression.
RESULTS
Across 32 studies, male circumcision was associated with decreased odds of prevalent HPV infections (odds ratio, 0.45; 95% CI, 0.34-0.61), a reduced incidence rate of HPV infections (incidence rate ratio, 0.69; 95% CI, 0.57-0.83), and an increased risk of clearing HPV infections (risk ratio, 1.44; 95% CI, 1.28-1.61) at the glans penis among male subjects. Circumcision conferred greater protection against infection at the glans than the shaft (odds ratio, 0.68; 95% CI, 0.48-0.98). Females with circumcised partners were protected from all outcomes.
CONCLUSIONS
Male circumcision may protect against various HPV infection outcomes, suggesting its prophylactic potential. Understanding the site-specific effects of circumcision on HPV infection prevalence has important implications for studies of HPV transmission.
Topics: Female; Humans; Male; Circumcision, Male; Human Papillomavirus Viruses; Papillomaviridae; Papillomavirus Infections; Sexually Transmitted Diseases
PubMed: 37011808
DOI: 10.1016/j.cmi.2023.03.028 -
EBioMedicine Jun 2024Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and... (Review)
Review
BACKGROUND
Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations.
METHODS
We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070).
FINDINGS
The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer.
INTERPRETATION
The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease.
FUNDING
National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.
Topics: Humans; Papillomavirus Infections; Neoplasms; Risk Factors; Papillomaviridae; Female; Systematic Reviews as Topic
PubMed: 38744109
DOI: 10.1016/j.ebiom.2024.105155 -
The American Journal of Surgical... Dec 2023We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics....
Incidence and Clinicopathologic Characteristics of Human Papillomavirus-independent Invasive Squamous Cell Carcinomas of the Cervix: A Morphologic, Immunohistochemical, and Human Papilloma-Virologic Study of 670 Cases.
We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human papillomavirus (HPV) mRNA and immunohistochemistry for p16 and p53. Tumors were HPVI if negative by HPV ISH and they failed to show diffuse p16 positivity by immunohistochemistry, and human papillomavirus-associated (HPVA) if positive by HPV ISH. Ten HPVI SCCs and 435 HPVA SCCs were identified; 2 cases were equivocal and excluded from analysis. The overall rate of HPVI SCC was low (2%) but was higher among older patients (7% in patients above 60 y of age and 17% in patients above 70 y of age). Compared with HPVA, patients with HPVI SCC were significantly older (median age, 72 vs. 49, P <0.001) and diagnosed at a higher stage (40% vs. 18% with stage III/IV disease, P =0.055). p53 expression was varied; 2 cases (20%) had null expression and 8 (80%) had wild-type expression. HPVI SCCs were heterogenous, with keratinizing, nonkeratinizing, and warty morphologies observed. Several cases had a precursor lesion reminiscent of differentiated vulvar intraepithelial neoplasia, with prominent basal atypia and hypereosinophilia or a basaloid-like morphology. Two patients (20%) had distant recurrences within 12 months, and 3 (30%) died of disease during follow-up. HPVI SCCs are rare tumors that are more common among older patients with higher stage disease and have important clinical and histologic differences from HPVA SCCs.
Topics: Female; Humans; Aged; Human Papillomavirus Viruses; Papillomavirus Infections; Cervix Uteri; Carcinoma, Squamous Cell; Incidence; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms; Papillomaviridae; Papilloma; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 37702216
DOI: 10.1097/PAS.0000000000002122 -
Journal of the Egyptian National Cancer... Dec 2023The second most deadly gynecological cancer worldwide, cervical cancer is steadily on the rise in sub-Saharan Africa, while vaccination programs are struggling to get... (Review)
Review
INTRODUCTION
The second most deadly gynecological cancer worldwide, cervical cancer is steadily on the rise in sub-Saharan Africa, while vaccination programs are struggling to get off the ground. This systematic review's aim was to assess the prevalence and distribution of high- and low-risk HPV genotypes in West African women.
METHODS
Original studies were retrieved from PubMed/Medline, Embase, Scopus, Google Scholar, and Science Direct. In these studies, Human papillomavirus (HPV) DNA was assessed in cervical samples by polymerase chain reaction (PCR), Hybrid capture, and sequencing. The quality of the articles was assessed and the results were extracted and reviewed.
RESULTS
Thirty-nine studies from 10 West African countries were included for the systematic review including 30 for the pooled analysis. From an overall of 17358 participants, 5126 of whom were infected with at least one HPV genotype, the systematic review showed a prevalence varying from 8.9% to 81.8% in the general population. In contrast, the pooled prevalence of infection was 28.6% (n = 3890; 95% CI 27.85-29.38), and HPV-52 (13.3%), HPV-56 (9.3%), and HPV-35 (8.2) were the most frequent. Quadrivalent and nonavalent vaccines covered 18.2% and 55.8% of identified genotypes respectively.
CONCLUSION
Faced with this growing public health challenge in West Africa, it would be necessary for all its countries to have reliable data on HPV infection and to introduce the nonavalent vaccine. A study of the genotypic distribution of HPV in high-grade precancerous lesions and cervical cancer would be very useful in West Africa.
Topics: Humans; Female; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Vaccination Coverage; Papillomavirus Infections; Papillomaviridae; Genotype; Prevalence
PubMed: 38060078
DOI: 10.1186/s43046-023-00196-x -
Oral Oncology Jun 2024
Topics: Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Carcinoma, Squamous Cell; Papillomaviridae; Head and Neck Neoplasms; Human Papillomavirus Viruses
PubMed: 38702227
DOI: 10.1016/j.oraloncology.2024.106824 -
Head & Neck Nov 2023The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However,... (Meta-Analysis)
Meta-Analysis Review
The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16- were 269. The meta-analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82-0.94) and 0.94 (95% CI: 0.85-0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9-32.1) and 0.05 (95% CI: 0.02-0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology.
Topics: Humans; Papillomavirus Infections; Circulating Tumor DNA; Papillomaviridae; Oropharyngeal Neoplasms; Human Papillomavirus Viruses; DNA, Viral; Head and Neck Neoplasms
PubMed: 37715656
DOI: 10.1002/hed.27515