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Frontiers in Genetics 2022Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation,...
Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation, apoptosis. Moreover, retinoids have been used successfully for the treatment of certain malignancies, especially acute promyelocytic leukemia (APL) in adults and neuroblastoma in children. However, retinoids have not yet been translated into effective systemic treatments for most solid cancers. Some recent studies have shown that retinoids promote tumorigenesis. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of retinoids in the chemoprevention and treatment of cancers. We performed literature search of several electronic databases, including PubMed, Embase and Cochrane Library from 2000 January to 2021 November. Various outcomes were applied to investigate the potential of retinoids for prevention and treatment of cancers. The primary outcomes in this study were disease recurrence and clinical response. The secondary outcomes included overall survival (OS), cancer development, disease progression and event-free survival. We identified 39 randomized controlled trials with 15,627 patients in this study. Our results showed that lower recurrence rate and better clinical response were obtained in retinoids treated patients with cancer or premalignancy as compared with control. The differences were statistically significant (RR = 0.85, 95% CI = 0.74-0.96, = 0.01; RR = 1.24, 95% CI = 1.03-1.49, = 0.02, respectively). Retinoids treatment was not associated with improvement in overall survival, cancer development, disease progression or event-free survival. Subgroup analysis conducted based on cancer type showed that patients benefited from retinoids treatment in APL, renal cell carcinoma, hepatocellular carcinoma, lung cancer, Kaposi sarcoma, and complete hydatidiform mole. No significant therapeutic effect was noted in head and neck cancer, acute myeloid leukemia (AML), melanoma, breast cancer, bladder cancer, cervical intraepithelial neoplasia (CIN) or cervical carcinoma. Subgroup analysis based on tumor classification demonstrated that retinoids group obtained a lower recurrence rate and better clinical response than control group in solid cancers. In conclusion, clinical application of retinoids was associated with reduction in disease recurrence and improvement in clinical response, illustrating that retinoids play a key role in cancer prevention and therapy. Further research is needed to broaden the utility of retinoids in other types of cancers. PROSPERO, identifier CRD42022296706.
PubMed: 36437918
DOI: 10.3389/fgene.2022.1065320 -
International Journal of Molecular... Oct 2022Head and neck cancer (HNC) is an ascending and agressive disease. The search for new molecular markers is emerging to solve difficulties in diagnosis, risk management,... (Meta-Analysis)
Meta-Analysis Review
Head and neck cancer (HNC) is an ascending and agressive disease. The search for new molecular markers is emerging to solve difficulties in diagnosis, risk management, prognosis and effectiveness of treatments. Proteins related to apoptotic machinery have been identified as potential biomarkers. Caspase 3 is the main effector caspase and has a key role in apoptosis. The objective of this systematic review and meta-analysis is to review studies that analyze changes in Caspase 3 and Cleaved Caspase 3 expression both in oral premalignant disorders (OPMD) as well as in head and neck cancer (HNC). This study also proposes to review the prognostic values associated with HNC according to the expression of Caspase 3. Medline (via PubMed), EMBASE, Scopus, Cochrane, Web of Science and Grey Literature Database were screened from inception to june of 2022 and 18 studies were selected and 8 were included in the prognostic meta-analysis. Results related to the comparison of Caspase 3 expression demonstrated similar expression of Caspase 3 in HNC, with an average of 51.9% (9.5-98.1) showing high/moderate expression compared to 45.7% (14.6-84.7) in OPMD. Of interest, Cleaved Caspase 3 resulted incresed in HNC when compared with OPMD, being 73.3% (38.6-88.3) versus 22.9% (7.1-38.7). Pooled Fixed effect of HR values (95% CI) for OS related to Caspase 3 IHC expression in HNC patients was 1.48 (95% CI 0.95-2.28); also, the rate of heterogeneity was low, as revealed by I = 31%. For DFS was 1.07 (95% CI 0.79-1.45) with I = 0% and DSS showed a HR of 0.88 (95% CI 0.69-1.12) with I = 37%. Caspase 3 and Cleaved Caspase 3 expression could be linked with malignancy progression, but the expression of Caspase 3 did not influence the prognosis of patients with HNC.
Topics: Biomarkers; Caspase 3; Head and Neck Neoplasms; Humans
PubMed: 36233242
DOI: 10.3390/ijms231911937 -
Preventive Medicine Reports Dec 2022Oral cancer (OC) is a debilitating disease with a high mortality rate when diagnosed in advanced stage. Conversely, early-stage OC has a high survival rate, supporting a...
Oral cancer (OC) is a debilitating disease with a high mortality rate when diagnosed in advanced stage. Conversely, early-stage OC has a high survival rate, supporting a need for early detection programmes. A previous systematic review of clinical trials evaluating efficacy of screening for OC was inconclusive. This systematic review aimed to determine the impact of screening for oral lesions on reducing mortality and incidence of OC by looking at a broader spectrum of evidence. The search for randomized controlled trials and observational studies with a control group was conducted in PubMed, OVID, Cochrane, CINAHL and grey literature sources. Risk of bias for included studies was assessed with the tools developed by the Cochrane collaboration. Six out of two identified randomized trials and five observational studies had moderate to high risk of bias. Nevertheless, the predictions on impact of OC screening on incidence and mortality were similar across the majority of the studies. The -analysis concluded on a 26% decrease in OC mortality, and an 19% decrease in advanced OC cases as a result of OC screening in high-risk population. Three out of four studies did not identify an impact of screening on OC incidence. No positive impact of OC screening on incidence or mortality among general population was identified in the only available randomized trial. Consistency in the outcomes and the limitations of the few available studies suggest a need for real-life setting research to evaluate the overall effectiveness of screening for OC in high-risk population.
PubMed: 36189128
DOI: 10.1016/j.pmedr.2022.101987 -
World Journal of Methodology Jul 2022Smoking and chewing tobacco are associated with numerous oral mucosal lesions and conditions, often leading to cancer progression.
BACKGROUND
Smoking and chewing tobacco are associated with numerous oral mucosal lesions and conditions, often leading to cancer progression.
AIM
To investigate the prevalence of precancerous lesions and conditions among the Indian population.
METHODS
Systematic search was conducted for population or community-based observational epidemiological studies in PubMed, EMBASE, Web of Science, IndMED, Google Scholar, reports of the WHO South-East Asia Region, MOHFW India reports, Science Citation Index, WHO Index Medicus of the South-East Asian Region, (https://www.referencecitationanalysis.com/) and Open Grey from the earliest available up to 31 January 2022. The effect size was calculated for the prevalence of precancerous lesions and conditions.
RESULTS
One hundred sixty-two estimates from 130 studies yielded 52 high, 71 moderate, and seven low-quality studies from 823845. Point estimate based on cross-sectional studies for leukoplakia was 4.3% (95%CI: 4.0-4.6), oral submucous fibrosis was 2.7% (95%CI: 2.5-3.0), palatal lesions in reverse smokers and nicotine palatine were 5.8% (95%CI: 4.4-7.2), and Erythroplakia was 1.2% (95%CI: 0.7-1.7), and lichen planus was 1.1% (95%CI: 0.9-1.2). Amongst hospital-based studies, the pooled prevalence for Leukoplakia was 6.7% (95%CI: 6.0-7.3), oral submucous fibrosis was 4.5% (95%CI: 4.2-4.9), lichen planus was 7.5% (95%CI: 5.3-9.6), and erythroplakia was 2.5% (95%CI: 0.4-4.5), and palatal lesions in reverse smokers and nicotine palatini were 11.5% (95%CI: 8.0-15.0).
CONCLUSION
Precancerous lesions and conditions are prevailing problems among the Indian population. It is mainly due to tobacco use, the smokeless form of tobacco. The meta-analysis indicates that hospital-based studies have a higher effect size of 6.7% than community-based studies. Patients who have already developed this condition may be advised to reduce their exposure to the risk factor to prevent the condition from progressing further.
PubMed: 36159096
DOI: 10.5662/wjm.v12.i4.293 -
European Journal of Cancer Care Nov 2022The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to... (Review)
Review
INTRODUCTION
The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to review the evidence about factors associated with developing SPTs in patients with HNC.
METHODS
An updated systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and the search was performed in Pubmed and Scopus. Only original articles with a cohort or case-control design were included. Article quality was assessed with the Newcastle-Ottawa scale.
RESULTS
Thirty-six and two case-control studies were included, with quality medium (n = 5) to high (n = 33). Tobacco showed a significant association with SPT development, with risks ranging from 1.41 (95%CI: 1.04-1.91) to 5.52 (95%CI: 2.91-10.49). Regarding alcohol, risks ranged from 1.46 (95%CI: 1.12-1.91) to 21.3 (95%CI: 2.9-156). Location of the index tumour in the hypopharynx/oropharynx, absence of human papillomavirus and presence of a premalignant lesion also increased the risk of SPTs. More controversy was found for sex, age and other clinical factors of the tumour.
CONCLUSION
Toxic lifestyle habits and clinical factors were associated with the risk of SPTs in HNC patients. These findings may improve individualised prevention strategies in its follow-up.
Topics: Humans; Neoplasms, Second Primary; Head and Neck Neoplasms; Case-Control Studies
PubMed: 36117311
DOI: 10.1111/ecc.13699 -
Vaccine Sep 2022National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan.
METHODS
English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment - Normal, ASCUS, LSIL, HSIL and from histological assessment - CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta-analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596.
RESULTS
A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3-19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7-89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9-94·9) for cytological cases of HSIL, 76·9% (52·1-94·7) for histological cases of CIN3/AIS, and 75·7% (68·0-82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1-64·9), for quadrivalent genotypes was 58·6% (52·2-64·9) and for nonavalent genotypes was 71·5% (64·9-77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes.
INTERPRETATIONS
HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan.
Topics: Age Distribution; Alphapapillomavirus; Atypical Squamous Cells of the Cervix; DNA; Female; Genotype; Humans; Japan; Papillomaviridae; Papillomavirus Infections; Prevalence; Uterine Cervical Neoplasms; Vaccines, Combined; Uterine Cervical Dysplasia
PubMed: 36085257
DOI: 10.1016/j.vaccine.2022.07.052 -
Journal of Personalized Medicine Aug 2022Oral submucous fibrosis (OSMF) is a chronic premalignant condition and is characterized by fibroblastic change of lamina propria and stiffness of oral mucosa. Though... (Review)
Review
Oral submucous fibrosis (OSMF) is a chronic premalignant condition and is characterized by fibroblastic change of lamina propria and stiffness of oral mucosa. Though there are several treatment options available, the best agent is not yet identified. This study assessed the comparative efficacy and safety of medical interventions in the management of OSMF. A systematic review was performed to identify randomized controlled trials (RCTs) that compared the efficacy of interventions for OSMF with each other, or placebo. A network meta-analysis was performed, and the interventions were ranked according to their efficacy based on the surface under the cumulative ranking. (PROSPERO Registration no: CRD42021255094). Thirty-two RCTs comprising 2063 patients were eligible for quantitative analysis. In terms of therapeutic efficacy in the improvement of mouth opening Oxitard, a herbal formulation was ranked as the most efficacious agent, [MD, 10.29 (95%CI 6.34-14.25)] followed by combination therapy of Lycopene with corticosteroids and hyaluronidase [MD, 7.07 (95%CI 1.82-12.31)]. For improvement of burning sensation aloe vera was ranked first [MD, 6.14 (95%CI 4.58-7.70)] followed by corticosteroids with antioxidants [MD, 6.13 (95%CI 4.12-8.14)] and corticosteroids in combination with hyaluronidase with antioxidants [MD, 5.95 (95%CI 3.79-8.11)]. In terms of safety, most of the drugs were reported to cause mild adverse effects only. Significant inconsistencies could be identified in the analysis for both the outcomes assessed and were further explored. Our study highlighted the potential efficacy of several agents over placebo in the improvement of mouth opening and burning sensation in OSMF patients. However, the RCTs lacked methodological soundness. Well-designed studies with a larger number of participants with a rigorous randomization process and stringent methodology are recommended to strengthen the results obtained, which may help to construct a clinical guideline for OSMF management.
PubMed: 36013221
DOI: 10.3390/jpm12081272 -
Journal of the European Academy of... Jan 2023Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for... (Review)
Review
Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.
Topics: Humans; Bowen's Disease; Keratoacanthoma; Keratosis, Actinic; Papillomavirus Infections; Papillomaviridae; DNA, Viral; Skin Neoplasms; Carcinoma, Squamous Cell; Keratinocytes; Papillomavirus Vaccines
PubMed: 36000380
DOI: 10.1111/jdv.18548 -
Postepy Dermatologii I Alergologii Jun 2022Human papillomavirus (HPV) infection is mainly a problem of the female reproductive tract. It can occur in the oral cavity as well. Commonly HPV infections are...
INTRODUCTION
Human papillomavirus (HPV) infection is mainly a problem of the female reproductive tract. It can occur in the oral cavity as well. Commonly HPV infections are subclinical, without any visible symptoms, and last no longer than 2 years. Usually the clinical manifestation of HPV infection is benign, but in some cases it can also promote malignant transformation. In the paper we have tried to estimate the prevalence of HPV detected in samples of oral leukoplakia (OLK), the most common premalignant lesions of the oral mucosa.
AIM
To review the current literature to estimate the prevalence of HPV (HPV DNA) detected in samples of oral leukoplakia.
MATERIAL AND METHODS
We searched PubMed/Medline, Scopus, and Cochrane Library databases for studies that examined the prevalence of HPV in leukoplakia with HPV DNA detection by polymerase chain reaction.
RESULTS
HPV positive cases in OLK ranged from 0% to 100% in studies. The overall HPV prevalence in leukoplakia was 6.66%. The prevalence of HPV 16 positive cases was 2.95%. The high-risk HPV prevalence was 5.16%, when the low-risk HPV prevalence was 3.32%. When dysplasia is mentioned, HPV was detected in 19.56% of lesions with dysplasia, compared to 38.16% among non-dysplastic lesions.
CONCLUSIONS
Further studies should be extended also to include low-risk HPV and compare its prevalence with presence of dysplasia in leukoplakia. Besides, leukoplakia and other premalignant lesions can no longer be treated as one lesion.
PubMed: 35950127
DOI: 10.5114/ada.2021.107269 -
BMJ (Clinical Research Ed.) Aug 2022To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment.
DESIGN
Systematic review and meta-analysis DATA SOURCES: PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021.
REVIEW METHODS
Studies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was implemented for the primary outcome. Observational studies and randomised controlled trials were analysed separately from post hoc analyses of randomised controlled trials. Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals.
RESULTS
22 articles met the inclusion criteria of the review; 18 of these studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational studies, two randomised controlled trials, and four post hoc analyses of randomised controlled trials). The risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated (11 studies, 19 909 participants; risk ratio 0.43, 95% confidence interval 0.30 to 0.60; I=58%, τ=0.14, median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18 (six studies, 1879 participants; risk ratio 0.26, 95% confidence interval 0.16 to 0.43; I=0%, τ=0). Confidence in the meta-analysis for CIN2+ overall and CIN2+ related to HPV16 or HPV18, assessed by GRADE, ranged from very low to moderate, probably because of publication bias and inconsistency in the studies included in the meta-analysis. The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large (three studies, 17 757 participants; 0.28, 0.01 to 6.37; I=71%, τ=1.23). Evidence of benefit was lacking for recurrence of vulvar, vaginal, and anal intraepithelial neoplasia, genital warts, and persistent and incident HPV infections, although the number of studies and participants in each outcome was low.
CONCLUSION
HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision. GRADE assessment for the quality of evidence indicated that the data were inconclusive. Large scale, high quality randomised controlled trials are required to establish the level of effectiveness and cost of HPV vaccination in women undergoing treatment for diseases related to HPV infection.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021237350.
Topics: Alphapapillomavirus; Female; Human papillomavirus 16; Humans; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccination; Uterine Cervical Dysplasia
PubMed: 35922074
DOI: 10.1136/bmj-2022-070135