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

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.

Prognostic outcomes of oral squamous cell carcinoma derived from proliferative verrucous leukoplakia: A systematic review

“…Finally, although a review on the prognosis of P-OSCC has recently been published (González-Moles et al, 2021), it was not guided by the most recent preferred reporting items for systematic reviews and meta-analyses checklist (Page et al, 2021) and included verrucous carcinomas as a malignant transformation type. Since lymph node and distant metastases are very rare in verrucous carcinomas and therefore have a better prognosis than OSCC (Harishankar et al, 2019), this can directly impact the real prognostic impact of the disease when compared to conventional OSCC.…”

“…Although some systematic reviews have focused on the study of malignant transformation of PVL (Iocca et al, 2020;Ramos-García et al, 2021), there is only one recent review dedicated to the prognosis of P-OSCC in the literature (González-Moles et al, 2021); however, it is focused exclusively on OSCC and does not provide information on recurrence and the number of metastases. The different prognoses observed in previously published observational studies (Bagan et al, 2011(Bagan et al, , 2020Gouvêa et al, 2010) can confound the understanding of the real prognosis of P-OSCC; therefore, it is important to test the hypothesis that P-OSCC have a different prognosis from conventional OSCC and thus require different therapeutic and follow-up approaches.…”

Hallmarks of Cancer Applied to Oral and Oropharyngeal Carcinogenesis: A Scoping Review of the Evidence Gaps Found in Published Systematic Reviews

“…Patients with carcinomas highly infiltrated by cytotoxic T cells and NK cells, such as colon cancer, have a better prognosis than those without strong effector cell infiltration [ 2 ]. Our group, in two studies [ 268 , 269 ], has reported that oral carcinomas developed on oral lichen planus and proliferative verrucous leukoplakia have a better prognosis than conventional oral carcinomas, which could be related to the strong inflammatory infiltrate observed in these tumours. Furthermore, organ transplant recipients from theoretically tumour-free donors under immunosuppression occasionally develop tumours from the donor, presumably because these neoplastic cells from the immunocompetent donor would be maintained at bay by their immune system [ 270 ].…”

State of Evidence on Oral Health Problems in Diabetic Patients: A Critical Review of the Literature

“…Our research group has also reported the increased risk of development of oral potentially malignant disorders (OPMD) experienced by diabetic patients compared to the general population [12]. OPMDs are a significant group of mucosal disorders that may precede the diagnosis of oral squamous cell carcinoma (OSCC) [13,178], among which are essentially oral leukoplakia [179,180], oral lichen planus (OLP) [181][182][183], proliferative verrucous leukoplakia [184][185][186], erythroplakia, and actinic cheilitis [187,188]. Patients diagnosed with OPMDs may have an increased susceptibility to develop cancer anywhere in their mouth during their lifetime [13].…”