Diagnostic role of p16/INK4A protein in Human Papillomavirus (HPV) induced cervical dysplasia

Abstract

Abstract:The p16/INK4A protein is a cellular regulatory polypeptide over-expressed in the presence of high levels of the Human Papillomavirus (HPV) coded E7 protein. This review outlines the use of p16 antigen staining in cervical biopsies as well as in PAP smears summarizing the corresponding literature and commenting the authors' own experience. The p16 antigen is a reliable marker for dysplastic cells in CINII/CINIII (HSIL) lesions as viewed in cervical biopsies. When PAP smears were examined at large scale screening for p16 antigenreactive and atypical cells, considerable variations could be found especially in ASCUS graded lesions. Therefore, the presence of p16-reactive atypical cells in PAP smears should be interpreted together with the cytological signs of dysplasia, such as the altered N/C ratio. In addition, women revealing p16-positive ASCUS/LSIL specimens should be examined for the presence of HPV DNA. Detection of HPV DNA alone, i.e. in the absence of cytological screening has a low predictive value, since the clearance of HPV may occur even in the absence of morphological alterations. Combined cytological as well as molecular follow up contributes to the efficiency of diagnostic and increases the probability of correct interpretation of the pre-cancerous lesions by non-invasive techniques.

The Diagnostic of Cervical Carcinoma: From Theory to Practice

“…Alternatively, 14% cases graded CIN III in the HE stained sections were interpreted CIN II according to the Ki-67 staining. A similar tendency to worse grading from the evaluation, the HE stained sections only was found by us in p16 staining [14]. According to our experience, the viewing of parallel sections stained for p16 as well as Ki-67 antigen markers is of great help at confirming the extent of dysplasia seen in CIN II and/or CIN III HSIL-graded sections.…”

“…Namely, the average positive rate among the smears, which was in the range of 1.5-1.9% during the last 6-years period, has reached 3.5% in the year 2015 (an increase of 180%). As already suggested in our previous paper [14], and confirmed by others, the probability of transition from LSIL and/or ASC-H cases into HSIL strongly depends on the presence of HPV as detected by one of the available HPV DNA tests [15,16]. The great majority of the ASCUS cases and up to 85% of LSIL cases (especially in the absence of HPV DNA) might undergo spontaneous healing as shown in next paragraph.…”

“…Such situation is less likely to appear in biopsy sections, where typical confluent distribution of p16 antigen positive cells at the parabasal epithelium layer is of essential help for correct interpretation of the result. In our previous paper [14], we focused our interest on unclear and/or ASCUS-graded smears, which were found HPV DNA positive by a probability of 8-10%, but have been p16 antigen positive with a higher probability ranging from 32 to 61%. The wide range of p16 antigen false positivity of atypical cells was found associated with the staining procedure itself, since the CYN-Tec cytology staining kit showed more clear-cut results, allowing to distinguish the proportion of really p16 antigen positive, but HPV unrelated atypical cells on hand, from artificially stained ones on other hand.…”