Prognostic value of HPV status and tumoral markers (p16/Ki67) in chilean patients with anal cancer

Abstract

Background: Anal cancer, a relatively rare malignancy, has been steadily increasing in risk groups such as male that have sex with men (MSM), male and female with HIV and HPV infection, and women with previous cancer of the genital tract. Squamous cell carcinoma of the head and neck, genital tract and anal canal are associated with high-risk HPV types. When HPV integrates in the host cell genome in squamous cells, the result is overexpression of the viral oncogenic proteins E6 and E7, which interact with cellular proteins to initiate neoplastic transformation and upregulation of p16INK4A and Ki-67 proliferation antigen. The increasing interand intra-observer variability in the diagnosis of dysplastic lesions makes necessary the use of these surrogate markers. We analyzed the prognostic role of HPV status and p16/Ki67 expression in malignant lesions of the anal canal.Methods & Materials: Retrospective study (2013-2016) of 38 patients of 19-78 years, average age 43.5 year-old. Of which 25 male (66%) and 13 female (34%). Histologic grade of biopsies were: Invasive carcinoma n = 8; ACIN II/III n = 8; condyloma n = 9; biopsies with benign anal lesions n = 14 (fistula, fissure, hemorrhoid).HPV detection. Nested-real time PCR of E6/E7 sequences that differentiate HPV of high and low oncogenic risk. Expression of p16INK4a and Ki67 was carried out by immunohistochemistry following manufacturing instructions. Clinical records were reviewed.Results: All 8 invasive carcinoma were HR-HPV and p16/Ki67 positive: 6 women, one with cervical cancer, one HIV + ,one with CML; one male HIV + with two biopsies and a history of condyloma.Of 8 ACIN II/III: 7 were males, 6 HIV + , 5 HR-HPV and 4 p16/Ki67 positive; one woman HIV + , HR-HPV, p16/Ki67 positive. Viral load was high in most invasive carcinoma and ACIN II/II HIV + patients. All condyloma cases were males: 5 LR-HPV, 2 HR/LR HPV, 2 HPV negative; all were p16/Ki67 negative. Most patientes with malignant lesions had history of condyloma. Benign lesions were all HPV and p16/Ki67 negative. All HR-HPV were HPV-16 with one HPV-18.Conclusion: HPV status and molecular markers expression are useful indicators of patients at risk of developing neoplasic lesions. Apparently condyloma are a risk factor for developing anal cancer.