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British Journal of Cancer Mar 2014A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup... (Review)
Review
BACKGROUND
A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells.
METHODS
PubMed, Embase, and the Cochrane Library were searched from 1980 until October 2012. We applied the following inclusion criteria: a minimum of 20 cases of site-specific OP-SCCs, and HPV and p16 results present. Studies were categorised into three groups based on their definition of p16 overexpression: verbal definition, nuclear and cytoplasmatic staining between 5 and 69%, and ≥70% staining.
RESULTS
We identified 39 studies with available outcome data (n=3926): 22 studies (n=1980) used PCR, 6 studies (n=688) used ISH, and 11 studies (n=1258) used both PCR and ISH for HPV diagnostics. The methods showed similar HPV-positive results. Overall, 52.5% of the cases (n=2062) were HPV positive. As to p16 overexpression, 17 studies (n=1684) used a minimum of 5-69% staining, and 7 studies (n=764) used ≥70% staining. Fifteen studies (n=1478) referred to a verbal definition. Studies showed high heterogeneity in diagnostics of HPV and definition of p16. The correlation between HPV positivity and p16 overexpression proved best numerically in the group applying ≥70% staining for p16 overexpression. The group with verbal definitions had a significantly lower false-positive rate, but along with the group applying 5-69% staining showed a worse sensitivity compared with ≥70% staining.
CONCLUSIONS
There are substantial differences in how studies diagnose HPV and define p16 overexpression. Numerically, p16 staining is better to predict the presence of HPV (i.e. larger sensitivity), when the cutoff is set at ≥70% of cytoplasmatic and nuclear staining.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Female; Genes, p16; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Proteins; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Risk Factors; Squamous Cell Carcinoma of Head and Neck; Young Adult
PubMed: 24518594
DOI: 10.1038/bjc.2014.42 -
Systematic review and meta-analysis of the papillomavirus prevalence in breast cancer fresh tissues.Breast Disease 2022Although widely studied, the role of HPV in the genesis of breast carcinomas remains elusive due to the diversity of results across studies, possibly caused by the wide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although widely studied, the role of HPV in the genesis of breast carcinomas remains elusive due to the diversity of results across studies, possibly caused by the wide methodological heterogeneity, some of them with inadequate methods.
OBJECTIVE
To verify the association between HPV and breast cancer through the meta-analysis of studies that used the best-recognized techniques for viral detection and tissue conservation.
METHODS
A systematic review and meta-analysis restricted to studies that detected HPV by PCR in fresh and frozen tissue from breast cancer were conducted to obtain greater homogeneity. PubMed, Scopus, Science Direct, Cochrane Library, and SciELO were searched until December 14, 2019. Search terms included "breast cancer" and "HPV" without language restrictions. Eleven studies were included in the meta-analysis. The pooled relative risks and 95% confidence interval (95% CI) were calculated, and heterogeneity was assessed using the I-squared (I2).
RESULTS
The selected studies had very low heterogeneity (2%). There is a 2.15 times higher combined relative risk (95% CI = 1.60-2.89) of detecting HPV in breast cancer than in cancer-free breast controls with a statistically significant p-value (p < 0.0001).
CONCLUSION
Our data support the association of DNA-HPV with breast carcinomas. Further studies are needed to find out which breast cancer subtypes this association is most frequent.
Topics: Breast Neoplasms; Female; Frozen Sections; Humans; Papillomaviridae; Papillomavirus Infections; Prevalence; Tissue Banks
PubMed: 34744058
DOI: 10.3233/BD-201032 -
BMJ Open Oct 2023We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3).
DESIGN
Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.
DATA SOURCES
PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022.
ELIGIBILITY CRITERIA
Phase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance.
RESULTS
12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported.
CONCLUSIONS
The efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied.
PROSPERO REGISTRATION NUMBER
CRD42022307418.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Papillomavirus Infections; Uterine Cervical Dysplasia; Papillomaviridae; Clinical Trials, Phase II as Topic
PubMed: 37879679
DOI: 10.1136/bmjopen-2022-069616 -
Sexually Transmitted Infections Sep 2016The human papillomavirus (HPV) vaccine is recommended for adolescent girls in many European countries, however there is huge variation in vaccine uptake. (Review)
Review
BACKGROUND
The human papillomavirus (HPV) vaccine is recommended for adolescent girls in many European countries, however there is huge variation in vaccine uptake.
METHODS
A mixed methods systematic review to ascertain the level of HPV and HPV vaccine knowledge that exists among European adolescents. Two electronic databases, Ovid Medline and PsychInfo, were searched from origin to September 2014. Meta-analysis was performed for the two primary outcome measures ('have you heard of HPV?' and 'have you heard of the HPV vaccine?'), assessing for the correlation between gender and knowledge. This was supplemented with meta-synthesis for the remaining associations and secondary outcomes.
RESULTS
18 papers were included in the final review. Overall European adolescents had poor understanding of basic HPV and HPV vaccine knowledge. Meta-analysis identified that female adolescents are more likely to have heard of HPV (n=2598/5028 girls versus n=1033/3464 boys; OR 2.73, 95% CI 1.86-3.99) and the HPV vaccine (n=1154/2556 girls versus n=392/2074 boys; OR 5.64, 95% CI 2.43-13.07), compared to males. Age, higher education and a positive vaccination status were also associated with increased awareness. There was limited appreciation of more detailed HPV knowledge and uncertainty existed regarding the level of protection offered by the vaccine and the need for cervical screening post vaccination.
CONCLUSIONS
The delivery of HPV education to European adolescents needs to be re-evaluated, since at present there appears to be significant deficiencies in their basic knowledge and understanding of the subject. Increasing HPV knowledge will empower adolescents to make informed choices regarding participation with HPV related cancer prevention health strategies.
Topics: Adolescent; Europe; Female; Health Knowledge, Attitudes, Practice; Humans; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Parents; Patient Acceptance of Health Care; Reproductive Health; Uterine Cervical Neoplasms; Vaccination
PubMed: 26792088
DOI: 10.1136/sextrans-2015-052341 -
Anticancer Research Aug 2012Since the first reports (in 1979) suggesting an etiological role for human papillomavirus (HPV) in bronchial squamous cell carcinoma, literature reporting HPV detection... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the first reports (in 1979) suggesting an etiological role for human papillomavirus (HPV) in bronchial squamous cell carcinoma, literature reporting HPV detection in lung cancer has expanded rapidly, but a comprehensive meta-analysis has yet to be published. We performed a systematic review and formal meta-analysis of the literature reporting on HPV detection in lung cancer.
MATERIALS AND METHODS
MEDLINE and Current Contents were searched through April 2012. The effect size was calculated as event rates and their 95% Confidence intervals (CI), with homogeneity testing using Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of study-level co-variates (HPV detection method, geographical origin of study, cancer histology) on effect size, and potential publication bias was estimated using funnel plot symmetry (Begg and Mazumdar rank correlation, Egger's regression, and Duval and Tweedie's trim and fill method).
RESULTS
One hundred studies were eligible, covering 7,381 lung cancer cases from different geographical regions. Altogether, 1,653 (22.4%) samples tested HPV-positive; effect size was 0.348 (95% CI=0.333-0.363; fixed-effects model), and 0.220 (95% CI=0.18-0.259; random effects model). There was significant heterogeneity between the studies stratified by HPV detection technique, but the random effects in between-strata comparison was not significant (p=0.193). When stratified by i) different geographical regions, and ii) different histological types, the between-strata comparison was significant (p=0.0001). However, in meta-regression, HPV detection method (p=0.473), geographical origin (p=0.298) and histological type (p=0.589) were not significant study-level co-variates. No evidence for significant publication bias was found in funnel plot symmetry testing. In sensitivity analysis, all meta-analytic results seemed robust to all one-by-one study removals.
CONCLUSION
These meta-analytic results imply that the reported variability in HPV detection rates in lung cancer is better explained by geographical study origin and histological types of cancer than by the HPV detection method itself. In formal meta-regression, however, none of these three factors were significant study-level co-variates accounting for the heterogeneity of the summary effect size estimates, i.e. HPV prevalence in lung cancer.
Topics: Humans; Lung Neoplasms; Papillomaviridae
PubMed: 22843898
DOI: No ID Found -
Epigenomics Sep 2022The aim of this systematic review and meta-analysis was to assess the evidence for the diagnostic effectiveness of human papillomavirus (HPV) methylation biomarkers for... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis was to assess the evidence for the diagnostic effectiveness of human papillomavirus (HPV) methylation biomarkers for detection of cervical cancer. PubMed, Embase and Web of Science were searched. Nine articles focusing on HPV methylation for detection of precancerous and cancerous cervical lesions were included. The QUADAS-2 tool was used for quality assessment. The receiver operating characteristic (ROC) was the main diagnostic performance parameter extracted. Of the nine articles included in this study, seven were of moderate quality and two were of high quality. A meta-analysis of the ROC for 27 HPV methylation biomarkers revealed an overall pooled ROC of 0.770 (95% CI: 0.720-0.819; I: 98.4%; Q: 1537.4; p < 0.01). Four methylation biomarkers had strong diagnostic ability (ROC > 0.900), 17 were moderate (ROC: 0.7000-0.8999) and six were poor (ROC < 0.700). HPV methylation biomarkers hold significant promise as independent screening tests for the detection of cervical precancerous and cancerous lesions.
Topics: Alphapapillomavirus; Biomarkers; Early Detection of Cancer; Female; Humans; Methylation; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 36169190
DOI: 10.2217/epi-2022-0160 -
European Journal of Cancer (Oxford,... May 2014The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association.
METHODS
The pooled HPV prevalence was estimated using a random effects model and the I(2) statistic was used to describe the amount of heterogeneity. Potential sources of heterogeneity were evaluated by meta-regression and stratified analyses. For the studies on adenocarcinomas including control tissue, random effects estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
RESULTS
Thirty-seven studies were included. Among the 2630 adenocarcinomas, the pooled HPV prevalence was 11.2% (95% CI, 4.9-19.6%) with substantial between-study heterogeneity (I(2)=97.2%). The HPV prevalence varied by geographical region with highest prevalence in South America (45.1%, 95% CI, 21.9-69.4%), Asia (39.2%, 95% CI, 20.3-60.0%) and the Middle East (32.2%, 95% CI, 1.1-79.3%), and by detection method with the highest HPV prevalence in PCR-based studies. In the eight case-control studies, the pooled HPV prevalence was 36.8% (95% CI, 21.3-53.8%) in adenocarcinomas and 1.6% (95% CI, 0.0-9.6%) in controls giving an OR of 6.0 (95% CI, 2.0-17.9%) for the association between HPV and colorectal cancer. Among the 415 adenomas, the pooled HPV prevalence was 5.1% (95% CI, 0.0-17.8%; I(2)=93.7%).
CONCLUSIONS
HPV may be associated with a subset of colorectal cancers. Future large-scale multicenter case-control studies with data on risk factors such as lifestyle and sexual behaviour are needed.
Topics: Adenocarcinoma; Adenoma; Colorectal Neoplasms; Humans; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 24560489
DOI: 10.1016/j.ejca.2014.01.019 -
PharmacoEconomics May 2023Economic evaluations of vaccines should accurately represent all relevant economic and health consequences of vaccination, including losses due to adverse events...
Accounting for Adverse Events Following Immunization in Economic Evaluation: Systematic Review of Economic Evaluations of Pediatric Vaccines Against Pneumococcus, Rotavirus, Human Papillomavirus, Meningococcus and Measles-Mumps-Rubella-Varicella.
OBJECTIVES
Economic evaluations of vaccines should accurately represent all relevant economic and health consequences of vaccination, including losses due to adverse events following immunization (AEFI). We investigated to what extent economic evaluations of pediatric vaccines account for AEFI, which methods are used to do so and whether inclusion of AEFI is associated with study characteristics and the vaccine's safety profile.
METHODS
A systematic literature search (MEDLINE, EMBASE, Cochrane Systematic Reviews and Trials, Database of the Centre for Reviews and Dissemination of the University of York, EconPapers, Paediatric Economic Database Evaluation, Tufts New England Cost-Effectiveness Analysis Registry, Tufts New England Global Health CEA, International Network of Agencies for Health Technology Assessment Database) was performed for economic evaluations published between 2014 and 29 April 2021 (date of search) pertaining to the five groups of pediatric vaccines licensed in Europe and the United States since 1998: the human papillomavirus (HPV) vaccines, the meningococcal vaccines (MCV), the measles-mumps-rubella-varicella (MMRV) combination vaccines, the pneumococcal conjugate vaccines (PCV) and the rotavirus vaccines (RV). Rates of accounting for AEFI were calculated, stratified by study characteristics (e.g., region, publication year, journal impact factor, level of industry involvement) and triangulated with the vaccine's safety profile (Advisory Committee on Immunization Practices [ACIP] recommendations and information on safety-related product label changes). The studies accounting for AEFI were analyzed in terms of the methods used to account for both cost and effect implications of AEFI.
RESULTS
We identified 112 economic evaluations, of which 28 (25%) accounted for AEFI. This proportion was significantly higher for MMRV (80%, four out of five evaluations), MCV (61%, 11 out of 18 evaluations) and RV (60%, nine out of 15 evaluations) compared to HPV (6%, three out of 53 evaluations) and PCV (5%, one out of 21 evaluations). No other study characteristics were associated with a study's likelihood of accounting for AEFI. Vaccines for which AEFI were more frequently accounted for also had a higher frequency of label changes and a higher level of attention to AEFI in ACIP recommendations. Nine studies accounted for both the cost and health implications of AEFI, 18 studies considered only costs and one only health outcomes. While the cost impact was usually estimated based on routine billing data, the adverse health impact of AEFI was usually estimated based on assumptions.
DISCUSSION
Although (mild) AEFI were demonstrated for all five studied vaccines, only a quarter of reviewed studies accounted for these, mostly in an incomplete and inaccurate manner. We provide guidance on which methods to use to better quantify the impact of AEFI on both costs and health outcomes. Policymakers should be aware that the impact of AEFI on cost-effectiveness is likely to be underestimated in the majority of economic evaluations.
Topics: Child; Humans; Chickenpox; Cost-Benefit Analysis; Streptococcus pneumoniae; Human Papillomavirus Viruses; Rotavirus; Neisseria meningitidis; Mumps; Papillomavirus Infections; Vaccination; Immunization; Measles; Rotavirus Vaccines; Rubella
PubMed: 36809673
DOI: 10.1007/s40273-023-01252-z -
The Journal of General Virology Apr 2017Subclinical oral human papillomavirus (HPV) infection that persists for decades is likely to precede an HPV-driven squamous cell carcinoma of the head and neck, but... (Review)
Review
Subclinical oral human papillomavirus (HPV) infection that persists for decades is likely to precede an HPV-driven squamous cell carcinoma of the head and neck, but little is known about the natural history of oral HPV. We systematically reviewed and abstracted data from nine manuscripts that examined human immunodeficiency virus-negative and cancer-free subjects for oral HPV DNA to determine the pooled baseline prevalence and incidence of newly acquired oral HPV infections, and specifically for HPV-16. We also documented the clearance rate and the median time to clearance, where data existed. Of 3762 individuals, 7.5 % had an oral infection with any HPV type (1.6 % for HPV-16). Meta-regression analysis estimated the 12-month cumulative incidence to be 4.8 % (95 % confidence interval 3.2-7.3 %). The overall oral HPV clearance was reported to be 0-80 % between studies, and the median time to clearance from 6.5 to 18 months. Oral HPV-16 clearance was 43-83 %, and median time to clearance for HPV-16 was 7-22 months. Oral HPV prevalence, incidence and clearance vary considerably between published studies from different geographical regions. Further research is required to identify predictors of persistent oral HPV infection. Measurable baseline prevalence was observed in all studies, as well as non-trivial incidence of newly acquired oral HPV infections and incomplete clearance.
Topics: DNA, Viral; Genotype; Humans; Incidence; Mouth Diseases; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 28150575
DOI: 10.1099/jgv.0.000727 -
BMC Medicine Jul 2018Human papillomavirus (HPV) vaccination is safe and effective in preventing cervical cancer in females. As HPV infections can also induce cancers of the anus, penis and... (Review)
Review
BACKGROUND
Human papillomavirus (HPV) vaccination is safe and effective in preventing cervical cancer in females. As HPV infections can also induce cancers of the anus, penis and oral cavity, male vaccination is also advocated, but systematic reviews on efficacy and safety in males are lacking.
METHODS
We performed a systematic review on the efficacy, effectiveness and safety of HPV vaccination in males of any age. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to April 2017.
RESULTS
We identified 5196 articles and seven studies (four randomized controlled trials (RCTs), three non-randomized studies) were included, comprising a total of 5294 participants. Vaccine efficacy against at least 6-month persisting anogenital HPV 16 infections was 46.9% (95% confidence interval (CI) 28.6-60.8%), whereas efficacy against persisting oral infections was 88% (2-98%). A vaccine efficacy of 61.9% (21.4-82.8%) and 46.8% (- 20 to -77.9%) was observed against anal intraepithelial neoplasia grade 2 and grade 3 lesions, respectively. No meaningful estimates were available on vaccine efficacy or effectiveness against penile intraepithelial neoplasia grade 2 or 3, and no data were identified for anal, penile or head and neck squamous cell cancer. In participants who were HPV-seronegative and PCR-negative at enrolment, efficacy against all outcomes was higher as compared to seropositive and/or PCR-positive individuals. Risk of bias was low in three RCTs and high in one, while the three non-randomized studies were at serious to critical risk of bias. Grading of Recommendations Assessment, Development and Evaluation evidence quality was moderate to low for most outcomes.
CONCLUSIONS
HPV vaccination in males is moderately effective against persistent anogenital HPV infection and high-grade anal intraepithelial lesions in studies where the population consists mainly of HPV-infected males. Vaccine effectiveness was high in study groups comprising HPV-naïve males. This supports a recommendation for vaccination of boys before the onset of sexual activity with the goal of establishing optimal vaccine-induced protection. Mathematical modelling studies will still be needed to assess the effects of adding males to existing HPV vaccination programs in females.
TRIAL REGISTRATION
Prospective Register for Systematic Reviews (PROSPERO) registration CRD42016038965 .
Topics: Adult; Humans; Male; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Prospective Studies
PubMed: 30016957
DOI: 10.1186/s12916-018-1098-3