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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 -
Journal of Medical Virology Oct 2023Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in... (Meta-Analysis)
Meta-Analysis
Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in pathogenesis is still lacking. We first searched MEDLINE (PubMed), Embase, and Scopus databases (until October 2022), and systematically reviewed available literature. We then quantitatively estimated both pooled and genotype-specific prevalence of HPV DNA as well as the influence of various factors (e.g., geographical region, histological subtype, tissue/sample type) on computed effect size by means of random effects meta-analysis. In total, 379 studies comprising 17 129 cases of cervical adenocarcinoma were identified. The pooled HPV prevalence was 78.4% (95% confidence interval [95% CI]: 76.2-80.3) with a significant between-study heterogeneity (I = 79.4%, Q test p < 0.0001). Subgroup analyses indicated that the effect size differed substantially by geographical region (from 72.5% [95% CI: 68.7-76.1] in Asia to 86.8% [95% CI: 82.2-90.3] in Oceania) (p < 0.0001) and histological subtype of cancer (from 9.8% [95% CI: 5.5-17] in gastric-type to 85% [95% CI: 79.6-89.2] in usual-type cervical adenocarcinoma) (p < 0.0001). HPV16 and HPV18 were by far the most frequently detected viral strains with specific prevalence of 49.8% (95% CI: 46.9-52.6) and 45.3% (95% CI: 42.8-47.8), respectively. When stratified by continent or histologic variant, these genotype-specific results varied in a relatively limited manner. Altogether, these findings support that all histological subtypes of cervical adenocarcinoma are etiologically linked to high-risk HPV but to varying degrees. Therefore, a dual-criteria classification taking into account accurately both morphological and virological aspects could be an interesting evolution of the current binary World Health Organization classification, better reflecting the pathogenic diversity of the disease.
Topics: Female; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Prevalence; Papillomaviridae; Uterine Cervical Neoplasms; Adenocarcinoma; Genotype
PubMed: 37861377
DOI: 10.1002/jmv.29190 -
International Journal of Cancer Mar 2024We intended to update human papillomavirus (HPV) prevalence and p16 positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction... (Meta-Analysis)
Meta-Analysis
We intended to update human papillomavirus (HPV) prevalence and p16 positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16 positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16 positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16 positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.
Topics: Humans; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Head and Neck Neoplasms; Human papillomavirus 16; Human Papillomavirus Viruses; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 37861207
DOI: 10.1002/ijc.34763 -
Obstetrics and Gynecology Nov 2023To evaluate whether testing positive for human papillomavirus (HPV) before treatment is associated with cervical cancer recurrence and disease-free, cancer-specific, and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate whether testing positive for human papillomavirus (HPV) before treatment is associated with cervical cancer recurrence and disease-free, cancer-specific, and overall survival and to report the relationship of HPV to cervical cancer histology, stage, grade, tumor size, lymph node involvement, and treatment response.
DATA SOURCES
EMBASE and MEDLINE were searched from inception to January 27, 2022, with the use of MeSH terms and keywords relating to cervical cancer, HPV, and prognosis. ClinicalTrials.gov was not searched because of the nature of our review question.
METHODS OF STUDY SELECTION
Studies must have assessed HPV DNA or RNA in cervical pretreatment biopsies or cells from 20 or more patients with invasive cervical cancer followed up for any length of time and reported the effect of testing positive or negative for HPV on cervical cancer recurrence, disease-free survival, cancer-specific survival, or overall survival. We extracted data on HPV-detection methods, patient and tumor characteristics, and clinical outcomes.
TABULATION, INTEGRATION, AND RESULTS
Hazard ratios (HRs) and 95% CIs were pooled with a random-effects model. Meta-regression was performed to explore heterogeneity. Of 11,179 titles or abstracts and 474 full-text articles reviewed, 77 studies were included in the systematic review. Among these 77 studies, 30 reported on the relationship of HPV status to histology, 39 to cancer stage, 13 to tumor grade, 17 to tumor size, 23 to lymph node involvement, and four to treatment response. Testing positive for HPV was associated with better disease-free survival (HR 0.38, 95% CI 0.25-0.57; 15 studies with 2,564 cases), cancer-specific survival (HR 0.56, 95% CI 0.44-0.71; nine studies with 1,398 cases), and overall survival (HR 0.59, 95% CI 0.47-0.74; 36 studies with 9,169 cases), but not recurrence (HR 0.59, 95% CI 0.33-1.07; eight studies with 1,313 cases). Meta-regression revealed that the number of cases, tumor grade, specimen type, gene target, and HPV prevalence together explained 73.8% of the between-study heterogeneity.
CONCLUSION
This review indicates that HPV detectability in cervical cancer is associated with a better clinical prognosis.
SYSTEMATIC REVIEW REGISTRATION
https://osf.io/dtyeb .
Topics: Female; Humans; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Papillomavirus Infections; Neoplasm Recurrence, Local; Prognosis; Papillomaviridae
PubMed: 37856917
DOI: 10.1097/AOG.0000000000005370 -
Radiotherapy and Oncology : Journal of... Dec 2023Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment...
PURPOSE
Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment paradigms have been refined and continue to evolve in the modern era.
METHODS AND MATERIALS
This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A literature search of peer-reviewed publications was undertaken to identify works pertaining to the use of radiation for squamous cell carcinoma of unknown primary origin presenting as cervical lymph node metastases. Articles published from January 2002 to January 2023 with full text available on PubMed and restricted to the English language and human subjects were included. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.
RESULTS
While such breakthroughs as intensity-modulated radiotherapy, positron emission tomography, biomarker testing with immune-histochemistry, and minimally invasive surgical techniques such as transoral robotic surgery have fundamentally changed the approach to this disease in recent decades, controversies still exist with respect to the manner in which radiation is delivered. Although the incidence of head and neck unknown primary cancer is relatively low, questions regarding the necessity of comprehensive radiation using the age-old standard method of targeting the bilateral necks and entire pharyngeal axis to encompass all putative sites of mucosal disease persist.
CONCLUSIONS
Prospective evidence is lacking, and the available studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in work-up, treatment, inclusion criteria, and follow-up. Regardless, advances in science and technology have ushered in more precise approaches with a high degree of customization, particularly given the increased proportion of patients presenting with human papillomavirus-related disease.
Topics: Humans; Head and Neck Neoplasms; Human Papillomavirus Viruses; Meta-Analysis as Topic; Neoplasms, Unknown Primary; Papillomavirus Infections; Systematic Reviews as Topic
PubMed: 37844736
DOI: 10.1016/j.radonc.2023.109952 -
JAMA Otolaryngology-- Head & Neck... Nov 2023Head and neck cancers (HNCs) are often diagnosed at advanced clinical stages during their symptomatic phase, leading to a reduced treatment window and poor survival....
IMPORTANCE
Head and neck cancers (HNCs) are often diagnosed at advanced clinical stages during their symptomatic phase, leading to a reduced treatment window and poor survival. Screening programs have been suggested as a mitigation strategy.
OBJECTIVE
To examine the effectiveness of current HNC screening programs in improving diagnosis and survival in adults.
EVIDENCE REVIEW
This Preferred Reporting Items for Systematic Reviews and Meta-analyses-guided systematic review involved use of peer-reviewed, English-language journal articles identified from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials between January 1, 2001, and July 15, 2022. Snowballing was applied to retrieve more studies. Eligible articles were original clinical trials and observational studies presenting a universal or risk-targeted screening program of primary HNC in the adult population. Reporting quality was assessed using the JBI's critical appraisal tools.
FINDINGS
Database searches yielded 3646 unique citations with an additional 8 studies found via snowballing. Five reviewers assessed the full text of 106 studies. Sixteen articles were ultimately included in the review, involving 4.7 million adults (34.1%-100% male; median age, 30-59 years). Fifteen studies were based in Asia and 1 in Europe (Portugal). Five reported data from randomized clinical trials. An oral inspection conducted once or once every 2 to 3 years was described in 11 studies for screening oral cancer, while multistep screening involving Epstein-Barr virus serologic testing for nasopharyngeal carcinoma delivered every 1 to 4 years was presented in 5. In 4 trials and 6 observational studies, screening significantly increased the detection of localized (stage I/II) tumor or was associated with an increased proportion of diagnoses, respectively, regardless of the population and cancer subsites. Universal screening of asymptomatic adults improved 3- to 5-year overall survival but did not increase cancer-specific survival in 4 trials. Targeted screening improved overall and cancer-specific survival or was associated with improved survival outcomes in 2 trials and 2 observational studies, respectively. Studies had low to medium risks of bias.
CONCLUSIONS AND RELEVANCE
Evidence from the existing literature suggests that a risk-targeted screening program for oral and nasopharyngeal cancers could improve diagnosis and patient survival. Screening adherence, societal cost-effectiveness, and optimal risk stratification of such a program warrant future research, especially in low-incidence settings outside Asia.
Topics: Adult; Humans; Male; Middle Aged; Female; Epstein-Barr Virus Infections; Early Detection of Cancer; Herpesvirus 4, Human; Head and Neck Neoplasms; Mouth Neoplasms
PubMed: 37796524
DOI: 10.1001/jamaoto.2023.3010 -
Scientific Reports Oct 2023The involvement of human papillomavirus (HPV) in the prostate carcinogenesis is a controversial issue. The presented meta-analysis was carried out to systematize the... (Meta-Analysis)
Meta-Analysis
The involvement of human papillomavirus (HPV) in the prostate carcinogenesis is a controversial issue. The presented meta-analysis was carried out to systematize the currently available research results regarding this question. The meta-analysis includes case-control studies from 1991 to 2022, which were collected from publicly available bibliometric databases. The meta-analysis was performed using Meta-Essentials_1.5 software. We used Begg's and Egger's methods to assess publication bias. Cochran's Q test was used to assess heterogeneity and the I index was employed for calculating the variation in the pooled estimations. The analysis was based on data from 27 case-control studies, which in total yielded 1607 tumour tissue samples of prostate and 1515 control samples (317 samples of normal tissue, 1198 samples of benign prostatic hyperplasia (BPH)). According to the data obtained, there was high risk of prostate cancer by HPV infection in both cases. HPV was found in prostate cancer in 25.8% of cases, while in normal tissue samples the virus was detected in 9.2% of cases and in 17.4% with BPH as a control. In particular, more studies on the association of HPV and prostate cancer are needed to prove the role of HPV in the development of prostate cancer. In addition to the controversial question of whether HPV infection is associated with prostate cancer risk, it is worth considering whether the samples used as a control have an impact on the results. The impact of HPV in prostate tumour tissue samples on outcome should also be investigated.
Topics: Male; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Prostatic Hyperplasia; Papillomaviridae; Prostatic Neoplasms
PubMed: 37789036
DOI: 10.1038/s41598-023-43767-7 -
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 -
Journal of Medical Virology Sep 2023Accurate early detection of the human papillomavirus (HPV) status in head and neck cancer (HNC) is crucial to identify at-risk populations, stratify patients,... (Meta-Analysis)
Meta-Analysis
Accurate early detection of the human papillomavirus (HPV) status in head and neck cancer (HNC) is crucial to identify at-risk populations, stratify patients, personalized treatment options, and predict prognosis. Artificial intelligence (AI) is an emerging tool to dissect imaging features. This systematic review and meta-analysis aimed to evaluate the performance of AI to predict the HPV positivity through the HPV-associated diseased images in HNC patients. A systematic literature search was conducted in databases including Ovid-MEDLINE, Embase, and Web of Science Core Collection for studies continuously published from inception up to October 30, 2022. Search strategies included keywords such as "artificial intelligence," "head and neck cancer," "HPV," and "sensitivity & specificity." Duplicates, articles without HPV predictions, letters, scientific reports, conference abstracts, or reviews were excluded. Binary diagnostic data were then extracted to generate contingency tables and then used to calculate the pooled sensitivity (SE), specificity (SP), area under the curve (AUC), and their 95% confidence interval (CI). A random-effects model was used for meta-analysis, four subgroup analyses were further explored. Totally, 22 original studies were included in the systematic review, 15 of which were eligible to generate 33 contingency tables for meta-analysis. The pooled SE and SP for all studies were 79% (95% CI: 75-82%) and 74% (95% CI: 69-78%) respectively, with an AUC of 0.83 (95% CI: 0.79-0.86). When only selecting one contingency table with the highest accuracy from each study, our analysis revealed a pooled SE of 79% (95% CI: 75-83%), SP of 75% (95% CI: 69-79%), and an AUC of 0.84 (95% CI: 0.81-0.87). The respective heterogeneities were moderate (I for SE and SP were 51.70% and 51.01%) and only low (35.99% and 21.44%). This evidence-based study showed an acceptable and promising performance for AI algorithms to predict HPV status in HNC but was not comparable to the routine p16 immunohistochemistry. The exploitation and optimization of AI algorithms warrant further research. Compared with previous studies, future studies anticipate to make progress in the selection of databases, improvement of international reporting guidelines, and application of high-quality deep learning algorithms.
Topics: Humans; Artificial Intelligence; Papillomavirus Infections; Algorithms; Area Under Curve; Head and Neck Neoplasms; Human Papillomavirus Viruses
PubMed: 37691329
DOI: 10.1002/jmv.29080 -
Clinical Transplantation Nov 2023BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE AND BACKGROUND
BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients. Therefore, identifying the potential risk factors of BKV-HC after allo-HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV-HC remain debatable. Therefore, we conducted a systematic review and meta-analysis to identify the risk factors for BKV-HC, for early prevention of the occurrence of BKV-HC and to improve the quality of life and prognosis of allo-HCT recipients.
METHODS
We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV-HC.
RESULTS
Overall, 11 studies involving 2556 allo-HCT recipients were included in this meta-analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR = 1.32; 95% CI, 1.07-1.62; p = .009, I = 34%), haploidentical donor (OR = 1.84; 95% CI, 1.18-2.87; p = .007, I = 23%), myeloablative conditioning (OR = 1.76; 95% CI, 1.36-2.28; p < .0001, I = 45%), acute graft versus host disease (aGVHD) (OR = 2.73; 95% CI, 2.02-3.69; p < .0001, I = 46%), chronic graft versus host disease (cGVHD) (OR = 1.71; 95% CI, 1.12-2.60; p = .01, I = 0%), and cytomegalovirus (CMV) reactivation (OR = 3.13; 95% CI, 1.12-8.78; p = .03, I = 79%) were significantly associated with BKV-HC in the univariable analysis.
CONCLUSIONS
Our meta-analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV-HC.
Topics: Humans; Male; BK Virus; Retrospective Studies; Quality of Life; Cystitis; Hematopoietic Stem Cell Transplantation; Hemorrhage; Risk Factors; Graft vs Host Disease; Cytomegalovirus Infections; Polyomavirus Infections; Tumor Virus Infections
PubMed: 37676427
DOI: 10.1111/ctr.15121