Recurrence in Oral Leukoplakia: A Systematic Review and Meta-analysis

Abstract

The management of oral leukoplakia (OL) is challenging because of a high risk for recurrence and malignant transformation (MT), and recurrent OL is associated with a higher risk of MT than nonrecurrent OL. The present meta-analysis aimed to examine the association between OL recurrence and surgical techniques used for their management as well as their clinicopathological factors. Electronic searches were conducted in EMBASE, PubMed, Scopus, and Web of Science to retrieve studies reporting OL recurrence after surgery. The pooled proportion of OL recurrence after surgical excision was estimated. Subgroup analyses were conducted based on the surgical technique, data type, grades of epithelial dysplasia, anatomical subsites, clinical type and size of the lesion, surgical margin, and risk habits. Meta-regression analyses were conducted to identify the association between age, sex, and follow-up duration and OL recurrence. The risk of MT based on the recurrence status was also estimated. A network meta-analysis was performed to determine the surgical modality associated with the least OL recurrence. Eighty studies with a total of 7,614 samples and various surgical modalities (laser-based techniques, conventional scalpel surgery, cryosurgery, and photodynamic therapy) were included in the meta-analysis. A pooled proportion of recurrence of 22% was observed. Laser-based surgeries resulted in fewer OL recurrences than other surgical modalities, and the combination of laser excision and vaporization was identified to be the best treatment approach. OL in the retromolar area and multiple sites, nonhomogeneous OL, advanced age, female sex, inadequate surgical margin, retrospective data, and betel quid chewing habit were significantly associated with higher OL recurrence. Recurrent OL showed a 7.39 times higher risk of MT than nonrecurrent OL. These results suggest that the combination of laser excision and vaporization might reduce OL recurrence. Furthermore, OL in older patients, females, and nonhomogeneous OL need close monitoring after any surgical therapy.

Keywords: evidence-based practice; laser therapy; malignant transformation; oral potentially malignant disorders; risk factors; surgical excision.

Figure 1.

Preferred Reported Items for Systematic Reviews and Meta-Analyses flow diagram of study selection.

Figure 2.

Forest plots illustrating recurrence rates with respect to surgical modality and type of data.

Figure 3.

Forest plot showing proportions of recurrence of oral leukoplakia (OL) based on anatomical sites. OL in the retromolar area, multiple sites, and palate had higher proportions of recurrence.

Figure 4.

Forest plot illustrating the risk of recurrence between homogeneous oral leukoplakia (HOL) and nonhomogeneous oral leukoplakia (NHOL). The risk ratio of oral leukoplakia recurrence between HOL and NHOL is 0.62, indicating that HOL has 38% less risk of recurrence than NHOL.

Figure 5.

(A) Meta-regression analysis showed a flat regression line, indicating a nonlinear relationship and no association with the follow-up period. (B) Mean age (years) showed a linear and positive correlation, indicating that the recurrence rate of OL is higher in patients with advanced age. (C) The male-to-female ratio showed a linear and negative correlation, indicating that females have a higher propensity for recurrence than males.

Figure 6.

Forest plot for the risk of malignant transformation between recurrent and nonrecurrent oral leukoplakia (OL). Recurrent OL had a 7.39 times higher risk for malignant transformation compared to nonrecurrent OL.