Highly active antiretroviral therapy (HAART) and outcome of cervical lesions and high-risk HPV in women living with HIV (WLHIV): A systematic review and meta-analysis.

BACKGROUND: Collating evidence on the impact of highly active antiretroviral therapy (HAART) on the outcome of cervical lesions or human papillomavirus (HPV) infection among women living with HIV (WLHIV) is essential to inform cervical cancer prevention in this vulnerable group. METHODS: We performed a systematic review and meta-analysis of cohort studies that were conducted between January 1, 1996 and January 31, 2022 and reported on the association of HAART with any of the outcomes: incidence, progression, or regression of cervical lesions or acquisition or clearance of HPV infection in WLHIV. Random-effect analysis was used for summary statistics and heterogeneity was assessed through I2 statistic. The protocol for this review has been registered on the PROSPERO database with registration number CRD42021285403. RESULTS: Among 11 studies, the summary estimate of incident cervical lesions was lower in WLHIV on HAART (0.81, 95% CI 0.60-1.08). HAART was associated with lower risk of cervical lesion progression (0.76, 95% CI 0.64-0.92, I2 55.6%) and higher regression rate of these lesions (1.43, 95% CI 1.06-1.94, I2 81%). Though HPV acquisition was not significantly lower in HAART users (0.83, 95% CI 0.40-1.70), the clearance of HPV infection was higher in WLHIV on HAART (1.41, 95% CI 1.14-1.76, I2 2.4%). CONCLUSION: This review provides evidence that HAART assists in reducing the incidence and progression of cervical lesions and enhancing their regression in women living with HIV. Hence, the HAART regime should be recommended to all WLHIV with advice for adherence to allow for early immune reconstitution.

Podoplanin could be a predictive biomarker of the risk of patients with oral leukoplakia to develop oral cancer: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study is to identify and analyze the existing literature on the utility of podoplanin to predict the risk of malignancy development (MD) in patients previously diagnosed with oral leukoplakia (OL). METHODS: A systematic review and meta-analysis (SRMA) was performed though a search strategy using several electronic databases and a combination of keywords related to podoplanin and MD of OL, until 15 May, 2022 (PROSPERO CRD42022329326). Evaluation of the risk of bias (ROB) was performed using the Quality in Prognosis Studies Tool. The meta-analyses were estimated using fixed-effect models. RESULTS: From 421 articles, 6 studies were finally included, that enrolled 546 patients with OL, of whom 125 presented with an oral cancer during follow-up (32 to 90 months). Some limitations regarding the ROB were identified mostly related to small sample sizes, short follow-up times, lack of information on covariables in the included studies and lack of accuracy (including sensitivity and specificity). Meta-analysis of 6 studies reveal that high expression of podoplanin carries a pooled hazard ratio (HR) of 3.72 (95% CI, 2.40-5.76; p < 0.00001) for MD without statistical heterogeneity (I2  = 0%, p = 0.53). CONCLUSION: The results of this SRMA support the role of podoplanin immunohistochemical expression as a potential predictive biomarker to assess the risk of malignancy development in oral leukoplakia.

Risk Reversal of Oral, Pharyngeal and Oesophageal Cancers after Cessation of Betel Quid Users: A Systematic Review and Meta-Analysis.

BACKGROUND: Areca nut (AN), the principal ingredient of betel quid (BQ) has been categorized as a human carcinogen associated with various cancers of upper aerodigestive tract. However, there has been no attempt at summarizing the risk reversal of oral and other cancers after cessation of BQ with or without tobacco (BQ+T/BQ-T). OBJECTIVE: To analyze the effect of cessation of betel quid without tobacco (BQ-T) and with tobacco (BQ+T) on reversal of the risk of oral, pharyngeal and oesophageal cancers. METHODS: A systematic literature search was conducted for publications evaluating risk of these three cancers among current and former users of BQ-T or BQ+T. The overall as well as subgroup meta-relative risks (meta-RR) were estimated using random-effect models. RESULTS: A total of 14 studies, seven each providing estimates for BQ-T and BQ+T, were identified. For BQ-T and oral cancer, a 28.9% risk reversal was observed among former users (meta-RR 5.61, 95% CI 2.24-14.04) compared to current users (meta-RR 7.89, 95% CI 3.90-15.98). A risk reversal of 48% was noted for pharyngeal cancer - former users (meta-RR 2.50, 95% CI 1.43-4.38), current users (meta-RR 4.81, 95% CI 2.05-11.30). For oesophageal cancer, no appreciable difference in risk was observed between current and former users.For BQ+T and oral cancer the overall meta-RR indicated a higher risk in former than in current users. However, sensitivity analysis including only better-quality studies showed a modestly lower cancer risk in former than in current users. Compared to current users, the risk in former users who quit less than 10 years ago (meta-RR 1.21, 95% CI 0.90-1.63) was increased, but decreased in former users who quit more than 10 years ago (meta-RR 0.72, 95% CI 0.48-1.07). CONCLUSION: Our analysis highlights for the first time the potential of risk reversal for oral and pharyngeal cancers following cessation of BQ-T and for oral cancer in long-term quitters (greater than 10 years) of BQ+T. The suggestive evidence from this systematic review further supports the imperative need of a strong policy to reduce the initiation of BQ use and inclusion of interventions for BQ cessation in cancer control efforts especially in geographic regions where BQ chewing is prevalent.

Secondhand smoke exposure and oral cancer risk: a systematic review and meta-analysis.

OBJECTIVES: Inhalation of secondhand smoke (SHS) causes several diseases, including lung cancer. Tobacco smoking is a known cause of oral cancer; however, it has not been established whether SHS also causes oral cancer . The aim of this study was to evaluate the potential association between SHS exposure and the risk of oral cancer. METHODS: A systematic review and meta-analysis study (following the PRISMA guidelines) was developed to examine the studies reporting on the associations of SHS and the risk of oral cancer, employing a search strategy on electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, Open Grey, and ProQuest databases for dissertations) until 10 May 2020. Meta-analyses and sensitivity analyses were performed using random-effect models. The protocol was registered in PROSPERO (CRD42020189970). RESULTS: Following the application of eligibility criteria, five studies were included, comprising a total of 1179 cases and 5798 controls, with 3452 individuals exposed and 3525 individuals not exposed to SHS. An overall OR of 1.51 (95% CI 1.2o to 1.91, p=0.0004) for oral cancer was observed, without significant heterogeneity (I2=0%, p=0.41). The duration of exposure of more than 10 or 15 years increased the risk of oral cancer (OR 2.07, 95% CI 1.54 to 2.79, p<0.00001), compared with non-exposed individuals, without significant heterogeneity (I2=0%, p=0.76). CONCLUSIONS: This systematic review and meta-analysis supports a causal association between SHS exposure and oral cancer. Our results could provide guidance to public health professionals, researchers, and policymakers to further support effective SHS exposure prevention programs worldwide.

Dental Anomalies in a Brazilian Cleft Population.

OBJECTIVE: The aim of this study was to radiographically investigate the prevalence of dental anomalies outside the cleft area in a group of Brazilian patients with nonsyndromic cleft lip and/or palate (NSCL/P). DESIGN, PARTICIPANTS, AND SETTING: A retrospective analysis of 207 panoramic radiographs of patients with NSCL/P aged 12 to 45 years without history of tooth extraction and orthodontic treatment was performed. RESULTS: Dental anomalies were found in 75.4% of the patients, and tooth agenesis (29.2%) and supernumerary tooth (2.6%) were the most common anomalies. The risk of agenesis was higher among the individuals with cleft palate (CP) compared with individuals with cleft lip (CL) and cleft lip and palate (CLP) (agenesis: CP versus CL: odds ratio 6.27, 95% confidence interval 2.21-17.8, P = .0003; CP versus CLP: odds ratio 2.94; 95% confidence interval 1.27-6.81, P = .01). The frequency of dental agenesis was higher in patients with unilateral complete CLP (agenesis: P < .0001), incomplete bilateral CLP (agenesis: P = .0013), complete CP (agenesis: P < .0001), and incomplete CP (agenesis: P < .0001). The frequency of supernumerary teeth was higher in patients with bilateral complete CLP (P < .0001). The frequency of dental agenesis (P < .0001) and ectopic tooth (P = .009) was higher than the frequency estimated for general population. CONCLUSIONS: The prevalence of dental anomalies in patients with NSCL/P was higher than that reported in overall population. This study found preferential associations between dental anomalies and specific extensions of NSCL/P, suggesting that dental agenesis and ectopic tooth may be part of oral cleft subphenotypes.

Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Brazilian population with high African ancestry.

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is the most common orofacial birth defect, exhibiting variable prevalence around the world, often attributed to ethnic and environmental differences. Linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL ± P, mostly in European-derived or Asian populations. Genetic predisposition to NSCL ± P is ethnicity-dependent, and the genetic basis of susceptibility to NSCL ± P likely varies among populations. The population of Brazil is highly admixed, with highly variable ancestry; thus, the genetic determinants of NSCL ± P susceptibility may be quite different. This study tested association of 8 single-nucleotide polymorphisms (SNPs), previously identified by genome-wide studies in other populations, with NSCL ± P in a Brazilian population with high African ancestry. SNPs rs560426, rs642961, rs1530300, rs987525, rs3758249, rs7078160, rs17085106, and rs13041247 were genotyped in 293 Brazilian patients with NSCL ± P and 352 unaffected Brazilian controls. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphic markers to characterize genetic ancestry. The average African ancestry background was 31.1% for the NSCL ± P group and 36.7% for the control group. After adjustment for ancestry and multiple testing, the minor alleles of rs3758249 (OR: 1.58, 95% CI: 1.25-2.01, P = 0.0001) and rs7078160 (OR: 1.59, 95% CI: 1.21-2.07, P = 0.0002) were significantly associated with risk of NSCL ± P. Polymorphisms located in IRF6 (rs642961) and 8q24 (rs1530300 and rs987525) showed marginal associations in this Brazilian population with high African ancestry. These results indicate that rs3758249 at 9q22 and rs7078160 at 10q25.3 represent risk loci for NSCL ± P in the Brazilian population with high African ancestry.