351 Assessment of HPV infection and p16INK4A and Ki67 expressions in vaginal intraepithelial neoplasia

Introduction/Background* The term vaginal intraepithelial neoplasia (VaIN) refers to a premalignant lesion that has the potential to progress to invasive cancer. VaIN is a very rare disease and represents less than 1% of all female genital intraepithelial neoplastic lesions. Several studies have shown that high-risk (hr) HPV infection is an important factor in the development of VaIN. Although p16INK4A/Ki67 markers have been studied many times in cervical dysplastic lesions, they have rarely been used in vaginal dysplastic lesions. In the present study, we aimed to analyze the role of p16 and Ki67 levels on the progression or regression of VaIN together with HPV infection in vaginal epithelial cells with neoplastic changes. Methodology Cases of VaIN1, and VaIN2/3 were retrospectively identified from the surgical pathology files at the Department of Pathology, Istanbul Medical Faculty, Istanbul University from 2003 to 2020. A total of 10 cases of VAIN1, and 38 cases of VAIN2/3were identified. The primary endpoints of the study were the recurrence of VAIN and progression to vaginal carcinoma. Result(s)* Most of HPV positive cases (22 out of 36) were infected with HPV16 subtype (61.1%). One patient had HPV18 subtype (5.9%) infection. There was a significant correlation between the expression of p16INK4A and Ki67 together with the disease recurrence. Patients with strong expression of both p16INK4A and Ki67 had a significantly higher disease recurrence (p=0.010). Furthermore, we observed that the patients with strong expression of p16INK4A and Ki67 together, had the recurrence of the disease less than 12 months (p=0.041). Patients with strong expression of both p16INK4A and Ki67 had a significantly higher disease progression to invasive cancer (p=0.015). hr HPV positivity was significantly related with moderate or strong expression of p16 and ki67 (p=0.002). Conclusion* Strong expressions of p16INK4A and Ki67 together in vaginal tissue, had a significantly higher risk of recurrence. Furthermore, with strong expression of both markers together, the disease recurred more rapidly. In addition, strong expression of both markers might be associated with malignant progression. Finally, rate of infection with HPV18 subtype might be less than expected in patients with VaIN. These results need to be confirmed in future prospective studies.