Currently, no specific treatment modality has proven to be effective in the management of the PVL, either to slow down its progression toward malignant transformation and limit the high frequency of recurrence [2, 14]. Therefore, the patients with PVL need multiple biopsies over time to identify the histologic status of this progressive disorder .
The conventional treatment of PVL is surgical excision, although complete removal of the lesions may be challenging because of the multifocal manifestation of the oral lesions . This approach can lead to significant morbidity and compromised quality of life. However, the presence of HPV-16 infection associated with epithelial dysplasia can justify—as the present case—the wide surgical excision of the affected site, trying to minimize the operational invasiveness. A systematic literature review found that there is a potentially causal association between oral leukoplakia infected by HPV 16 and epithelial dysplasia, as well as with oral squamous cell carcinoma (OSCC) . It is important to consider that the biopsy sampling represents a powerful tool to demonstrate the relationship between HPV infection and oral dysplasia, since it has been shown that HPV DNA in exfoliated cells is not associated with HPV DNA detection in OSCCs [13, 15]. Furthermore, the multifocal development of the PVL lesions draws attention to the risk of field cancerization model, making the field mapping mandatory during the course of multiple biopsies sampling. The oncogenic potential of the HPV infection is attributable to its ability to insert specific DNA fragments of the early genes E5, E6, and E7 into the host cell genome. As a result of this integration, some key functions of tumor suppressor factors such as p21, p53, and pRb pathways are inhibited, leading to defects in apoptosis, DNA repair mechanisms, cell cycle regulation, and finally to . In the current case, the choice of the laser excision of the whole dysplastic lesion was made in the attempt of achieving a viral contamination abatement through a minimally invasive procedure. As a matter of fact, the lateral expansion of the viral particles into the scar tissue maintains the infectivity in the tissue repair and permits the viral replication cycle, whereas the lack of activity of late proteins in the cells holds the primary infection in the basal layer, permitting recurrent infections . It seems likely that the use of the laser surgery can induce—through the photo thermal effect—denaturation of the virus proteins in infected cells, extending the heat achieved by the high temperatures to areas beyond the lesion margins, thereby reducing the amount of infected tissue . These findings have been confirmed by the lower viral load values in samples obtained at 20 days after surgery when using the diode laser . Additionally, as regard the decision-making process in the surgical treatment of PVL with low grade dysplasia, it should be considered that no clinical characteristics—clinical appearance, lesion color, lesion surface—showed any significant correlation with malignant transformation to detect oral cancer in the early stage . As previously reported, the tongue and gingiva are the most common transformation sites in PVL lesions, and it has been emphasized, in particular, the importance of the gingival surveillance, as described in the present case [6, 21]. Taking into account the high recurrence rate in the clinical course of PVL, the abovementioned surgical management was primarily directed to keeping under control the viral load of HPV infection and the potential progression of epithelial dysplasia to malignant transformation. Finally, particular vigilance should be turned to the periodontal status of PVL patients, since it is more likely that OSCCs in PVL areas are located in the masticatory mucosa, particularly in the gingiva. Moreover, periodontal disease has been associated with a small, but statistically significant, increase in overall oral cancer risk, which persisted among non-smokers [6, 22,23,24,25].
Although recurrence and progression are very common in the PVL lesions, whether the microscopic evaluation of the tissue sample confirms the HPV infection associated with mild dysplasia, the laser excision can be considered as surgical option. Biopsy mapping and complete laser excision of PVL tissue associated with epithelial dysplasia appear to be reliable, reproducible procedures associated with low complications and morbidity rates in terms of preventing malignant transformation. Strict follow-up is recommended for patients with PVL associated with HPV-16 infection and low grade dysplasia to detect oral cancer at an early stage.
Nonsurgical therapeutic approaches for PVL have been considered such as external beam radiation therapy, cryotherapy, topical vitamin, and topical chemotherapy, but with little success. Cryosurgery, photodynamic therapy, and antiviral methisoprinol therapy have also been suggested with significant benefit. In the future, anti-HPV, anti-TGF, and pro-apoptotic management strategies may be assessed [2, 4, 14].