## 4 Discussion
presented a retrospective study of 205 cases of SP in immunocompromised patients, with only 6 relapses occurring in a 24 month follow-up period. [PERSON] et al. published a case-controlled study of immunocompromised patients for which surgical excisions were performed by cold blade (22 patients with SP) and CO2 laser (12 patients with SP). After 15 months, two recurrences occurred in both groups. [PERSON] et al. stated that the treatment of choice for HPV-related lesions of the oral cavity is surgical excision, primarily with traditional surgery, and secondarily with any other method, among which laser is an excellent alternative. In [PERSON]'s reports in 2000, [PERSON] et al. in 2001, and [PERSON] et al. in 2002, three different lesions were treated in immunocompromised patients [17; 26; 27]. Relapses occurred in all three studies, and [PERSON] reported the malignant transformation of the lesion. In 2003, [PERSON] et al. also reported the malignant transformation of an SP in an immunocompromised patient after 36 months [14]. However, in studies using larger sample size, different outcomes were reported. In 1992, [PERSON] et al. did not report recurrence in 13 immunocompromised patients treated with laser excision. In 2012, [PERSON] did not report recurrence after treatment of five immunocompromised patients. In 2015, [PERSON] et al. reported the absence of complications and only one recurrence (with the lesion disappearing after a second application) in treating 174 lesions in 170 immunocompromised patients. In the larger sample size studies, the authors reported excellent patient tolerance and a short duration of surgical sessions [28; 29; 30]. Interestingly, a split-mouth study conducted by [PERSON] et al. in 2012 of 10 lesions in 5 patients treated with both CO2 lasers and electroautery reported that the viral load three weeks after surgery was significantly lower or absent in laser-treated areas [29]. The viral load may influence the recurrence of lesions and infections, from which potentially malignant lesions could arise. Furthermore, it would be appropriate to assess the viral load in immunocompromised patients and in those lesions that tend to recur, perhaps due to an ineffective immune response. The therapeutic approach to benign HPV neoformans is to completely remove the lesions. However, other factors should be considered from the patient's pharmacological and systemic history to better identify the causes of infection. Factors, such as the need to attenuate any risk behaviors; repeated mechanical trauma; irritative stimuli that may result from sharp edges of fillings, teeth, rough or abrasive surfaces, and incongruuous prostheses should be identified to help the patient adopt an accurate oral hygiene program to reduce the potential risk of malignant transformation. Particular attention to gum disease and avoiding risky behaviors, such as cigarette smoking and alcohol consumption, should be advised. We subjected numerous therapeutic strategies, adopted by clinicians and reported by scholars in the scientific literature, to a systematic review and meta-analysis. The limitations of the studies analyzed were primarily small samples, short duration of treatments, absent or insufficient follow-up, absence of overlapping and reliable standard verification questionnaires, and inhomogeneity in treatment outcomes. The limit of this study is clearly the presence of small sample papers and case reports, but the authors thought it could be interesting to include different therapeutic strategies, such as targeted therapies. Research is moving toward more targeted therapies, especially for lesions that have appeared in immunocompromised patients undergoing highly active antiretroviral therapy (HAART), such as limiquimod and cidofovir. For these, RCTs and case-controlled studies with large patient sample sizes and longer follow-up periods and standardization of treatment duration and modalities are needed. Lesion excision is the first line of therapy to be adopted, regardless of the instrument used.