Prognosis Parameters of Oral Carcinomas Developed in Proliferative Verrucous Leukoplakia: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Proliferative verrucous leukoplakia is considered by the WHO as an oral potentially malignant disorder that presents the highest tendency to recurrence and malignant transformation rate. However, to date limited evidence-based prognostic data for oral carcinomas developed in patients with proliferative verrucous leukoplakia (PVL-OC) have been published, and these carcinomas probably perform better than conventional oral carcinomas. In this study we present a systematic review and meta-analysis to evaluate the current evidence in relation to the prognosis of oral carcinomas developed in patients PVL-OC. ABSTRACT: Proliferative verrucous leukoplakia (PVL) is contemplated by the World Health Organization (WHO) as an oral potentially malignant disorder (OPMD) with a high the highest malignant transformation ratio among all OPMD (approximately 50%). Our aim was to evaluate the current evidence in relation to the prognosis of oral carcinoma developed in patients with proliferative verrucous leukoplakia (PVL-OC). We searched PubMed, Embase, Web of Science and Scopus for published studies (upper date limit = June 2021). We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses, examined inter-study heterogeneity through subgroup and meta-regression analyses, and performed sensitivity and small-study effects analyses to test the stability and reliability of results. 23 studies met inclusion criteria (505 patients with PVL, of which 288 developed a total of 504 carcinomas). The meta-analyzed overall mortality rate was 21.29% (pooled proportions [PP] = 95% confidence intervals [CI] = 8.77–36.36) for PVL-OC, clearly lower than the 34.7–50% mortality rate for conventional oral cancer reported in previous studies. In comparison with a single study reporting on conventional oral cancers, mortality was significantly lower for PVL-OC (hazard ratio = 0.29 [95%CI = 0.10–0.89], p = 0.03). Univariable meta-regression verified that case series that presented higher proportions of verrucous carcinomas showed a better survival of PVL-OC (p = 0.05), but not with higher proportion of oral squamous cell carcinomas (p = 0.74). Significant differences were not found for other relevant variables such as follow up period (p = 0.44) or multiple tumor development (p = 0.74). In conclusion, PVL-OC show favorable prognostic parameters, especially with regard to the mortality rate.