Genotyping of Human Papilloma Virus Infections and Phenotyping of Tumor Infiltrating Lymphocytes in Iraqi Patients with Uterine Cervical Neoplasia

Abstract

ABSTRACT:BACKGROUND:Among most basic and clinical investigations for detection and genotyping HPV, only In Situ Hybridization (ISH) is effective in studing the relation of HPV genome to that histopathological entity. Tumor Infiltrating Lymphocytes (TILs) represent the local cellular immune response against both cervical cancer and the associated HPV.OBJECTIVE:This study is aimed to investigate ISH in detection and genotyping of HPV and immunohistochemical (IHC) study in phenotyping of TILs in Iraqi women with different grades of cervical neoplasia.MATERIALS AND METHODS:This retrospective research included a total number of 129 cervical tissue blocks , 64 with invasive and 27 with pre-invasive cervical neoplasia,12 with condylomata acuminata,11 with chronic cervicitis and 15 with apparently- healthy cervices .Molecular detection and genotyping of HPV DNA were performed by using ISH whereas immunophenotyping was done by IHC using monoclonal antibodies for that specific CD markers representing some of TILs.RESULTS:The overall prevalence of HPV DNA in total group of invasive cervical neoplasia was 28.4% , 12 out of 48(25%) with squamous cell carcinoma(SCC) and 8 out of 16(50%) with adenocarcinoma (AC). HPV 16 constituted (58.3%) of HPV- positive invasive cervical SCC , where as HPV 31/33 and lastly HPV 18 constituted (25%) and (16.7%) , respectively .In AC group, HPV 16, 18, 31/33 occupied 50% , 25% , 12.5% of this group, respectively .The prevalence of HPV DNA in pre-invasive cervical neoplasia group was 22.2%. While no case with HPV 18 was detected , HPV 16 and HPV 31/33 genotypes occupied 40% and 60% , respectively .Although CD3+,CD4+and CD8+ lymphocytes showed high mean values , significant differences present only between HPV DNA- positive tissue blocks and control group (p<0.05) . The CD20+and CD56+ lymphocytes showed low mean values.Compared to control group,however,statistical analysis showed significant differences (p<0.05) regarding CD20+ and non-significant regarding CD56+ lymphocytes .CONCLUSION:Using ISH proved more powerful and sensitive tool in revealing precised effects of HPV in cervical neoplasia compared to histopathological examination .High mean values of CD4+ and CD8+ versus low mean values of CD20+ and CD56+ lymphocytes could reflect an important and specific role of these cellular responses against HPV viruses during initiation and progression of HPV-associated cervical cancers.