Objective: The vast majority of HPV infections are cleared spontaneously, without treatment. If the viral infection persists, the risk of developing a precancerous lesion increases as well as the risk of developing an invasive carcinoma. HPV genotyping is of clinical interest, since the risk of developing a precancerous lesion varies depending on genotype. A number of biomarkers that allow monitoring essential molecular events are likely to improve the detection of lesions that have a higher risk of progression as well as predict progression of the cervical lesion. Aim of the study is to explore the expression pattern of p16/Ki-67 immunocytochemical dual-staining depending on specific, most common oncogenic human papilloma virus (HPV) genotype in cytological diagnosed low-grade lesion (LSIL) and high-grade lesion (HSIL) on cervical smears.
Material and Methods: One hundred forty-six patients with HPV testing results were selected from accompanied gynaecological practice. All these patients underwent cytological diagnosis and from additional smear, immunostaining was performed using CINTecPlus Kit (Roche)
Results: Among 121 HPV positive patients, dual staining was positive in 69 (57%) patients, and 52 (42,9 %) of them had negative immunostaining. In group of 25 HPV negative patients, two of them had positive staining results. The overall prevalence of DNA HPV detection was 82,8% (121/146).Most frequent genotype was in the group of one or more other HPV types, then type 16, infection with multiple types which includes type 16 , than type 18 in 52,1%, 28,1%,14,8% and 4,9% respectively. Among 92 of patients with LSIL, positive p16/Ki67 staining was found in 46,7% (43/92) cases and was most frequent in patients with HPV infection type 16, one or more other types, multiple infections including type 16 and type 18 in 17,4%, 14,1%, 11,9% and 3,2% respectively. Twenty-six (89,7%) of twenty-nine patients with HSIL diagnosis had positive dual staining in group of other oncogenic types in 44,8%; with type16 in 27,6%; in the group of multiple type infection 13,8% and one patient with HSIL, had infection with type18 (3,4%).
Conclusion: These results represent a strong association between positivity for oncogenic types of HPV, p16/Ki-67 staining and severe cytological abnormalities proving ones again importance of detecting oncogenic types in protocol of handling patients with cervical pathology. This methodology could be used to detect unnoticed cervical lesions. The identification of prognostic biomarkers that can predict progression to invasive cancers is an important, but challenging area of biomarker research.
Hwang J.S.,Shroyer K.R. Biomarkers of cervical Dysplasia and Carcinoma, Journal of Oncology; 2012:doi:10.1155/2012/507286
Doorbar J.: papillomavirus life cycle organization and biomarker selection. Disease Markers, 2007;23(4):297-303.
Nakamura Y.,Matsumoto K, Satoh T, Nishide K et al. :HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicentre prospective study. Int J Clin Oncol.2015; 20(5): 974-81.
Killeen J.L. ,Dye T., Grace C., Hiraoka M.: Improved abnormal Pap smear triage using cervical cancer biomarkers. J Low Genit Tract Dis. 2014; 18(1):1-7.
WaldstrOm M., Christensen R.K.,Ornskov D.: Evaluation of p16/Ki67 dusl stain in comparisom with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion. Cancer Cytopathology 2013;121:136-45