## 4 Discussion  
The objective of this research was to combine data from various studies conducted on the treatment of benign HPV-related lesions of the oral cavity, thereby generating a single conclusive piece of data on the most effective treatment for the management of these lesions. Oral benign HPV-related lesions are relatively common. There are many treatment strategies proposed in the literature. However, a definitive and validated standard therapy has not yet been defined to achieve a low recurrence rate and low viral load. Regarding the current systematic review of the scientific literature of pharmacological and non-pharmacological treatment of oral HPV-related lesions, some considerations should be made. Due to this analysis's inclusion and exclusion criteria, many of the included studies had small sample sizes, short duration of treatments, insufficient follow-up, and inhomogeneity of the treatment outcomes. Additionally, several new targeted treatments are still under investigation, with no RCTs or case-control studies currently available. Therefore, available data on the effectiveness of these new treatments is lacking. Research is moving toward more targeted therapies, especially for lesions that have appeared in immunocompromised patients undergoing highly active antiretroviral therapy (HAART), such as imiquimod [14; 15; 16] and cidofovir, [17; 18; 19; 20]. For these, RCTs and case-control studies with large patient sample sizes and longer follow-up periods, as well as standardization of treatment duration and modalities, are needed. Additional HPV-related drug treatments, such as bleomycin, imidazoquinoline, and trichloroacetic acid, do not have application in the oral cavity and scientists appear to have no interest in experimenting with their application [21; 22; 23]. Furthermore, additional study is needed for applying interferon for long-term prevention of oral HPV recurrence. What can safely be inferred from this systematic review of the literature is that lesion excision is the first line of therapy to be adopted, regardless of the instrument used. In cases of multiple relapses, especially in immunocompromised or HAART patients, topical drug therapies, such as imiquimod and cidofovir, can be applied for several weeks with a high probability of success. The management of these lesions is important, both for limiting the spread of the virus and preventing the appearance of malignant lesions within the oral cavity. Therefore, new, randomized, case-controlled studies with large patient samples, adequate treatment duration, long-term follow-up, study of recurrence rate, and uniform result detection criteria are necessary to define a standard treatment of HPV-related oral cavity lesions. The most commonly recommended treatment of oral HPV-related lesions is surgical excision with a cold-blade scalpel. This instrument allows the complete excision of the lesion, therefore, lowering the viral load. It also allows an achievement of tissue fragment, characterized by defined peri-incisional margins, without any other structural alterations. However, this surgical intervention involves anesthesia, sutures, and bleeding. Laser excision can be performed using various wavelengths, thereby minimizing interaction with soft tissues while allowing for the collection of tissue samples. Biopsies performed with lasers have some advantages compared to those performed with a scalpel. Generally, these operations do not require suturing, and the healing at the collection site is faster in the initial stages [24]. Of the studies that we selected for analysis, 22 involved excision by laser, 13 involved excisions by cold blade, and one compared both techniques. The recurrence rate of laser-treated lesions is 5.98%, while the recurrence rate of cold-blade excision is 4.07%. The most extensive studies on cold-blade excision are the 2015 study by [PERSON] et al. and the 2019 study by [PERSON] et al. [13; 25]. [PERSON] et al.