Reliability of the CINtecTM p16INK4a immunocytochemical test in screening cervical precancerous lesions

Abstract

Background/Aim. Overexpression of p16INK4a has been found to be linked with genomic integration of high-risk human papillomavirus (HPV) and the developement of precancerous cervical intraepithelial lesions. The aim of this study was to examine is there a higher positive level of correlation between grade of histological dysplasia and p16INK4a level of expression in cervical smear, compared to results of Papanicolaou test. We also examined the correlation between HPV type, p16INK4a expression and Papanicolau test results. Methods. A total of 48 women with precanceorous cervical lesions and HPV cervicitis and 10 healthy women were enrolled in the study. Papanicolaou test, CINtecTM p16INK4a citological immunohistochemical test, polymerase chain reaction (PCR) HPV 16, 18, 31, 33 analysis and histopathology of the lesion were performed in all the patients. Results. Comparing the results of Papanicoulaou test and the grade of histological dysplasia, low-grade squamous intraepithelial lesion (LSIL) was confirmed in 38%, and high-grade squamous intraepithelial lesion (HSIL) in 69.2% of the patients (p > 0.05). Significant positive correlation was found between p16 overexpression and grade of histological dysplasia (p = 0.000). Overexpression p16 was found in 70% of LSIL and 94.4% of HSIL. Positive correlation was found between p16 overexpression and grade of dysplasia in Papanicolaou test (p = 0.011). In 38% of LSIL and 15% of HSIL cases p16 was not expressed. The most frequently found HPV type in PCR analysis was HPV16. Analysing the results of p16 test according to HPV status and Papanicolaou test rather heterogenous results were obtained. Conclusion. In the patients with precancerous cervical lesions a higher level of correlation was found between the grade of histological dysplasia and p16INK4a level of expression in the cervical smear, compared to the results of Papanicolaou test.Uvod/cilj. Utvrdjeno je da prekomerna ekspresija p16INK4a proteina ukazuje na genomsku integraciju visoko rizicnih humanih papiloma virusa (HPV) i razvoj premalignih intraepitelnih lezija grlica materice. Cilj rada bio je da se utvrdi da li kod bolesnica sa premalignim lezijama grlica materice postoji znacajnija pozitivna korelacija stepena ekspresije p16INK4a proteina u razmazu citoloskog brisa grlica materice sa stepenom histoloske displazije, u odnosu na nalaz Papanikolau testa. Osim toga, uporedjivana je HPV tipizacija sa nalazom p16INK4a proteina i Papanikolau nalazom. Metode. Ispitivanjem je obuhvaceno 48 bolesnica sa prekanceroznim promenama grlica materice i HPV cervicitisom i 10 zdravih zena. Svakoj bolesnici uradjen je Papanikolau test, CINtecTM p16INK4a citoloski imunohistohemijski test, HPV tipizacija lancanom reakcijom polimeraze na HPV tipove 16, 18, 31 i 33 i biopsija promene. Rezultati. Poredjenjem rezultata Papanikolau testa sa patohistoloskim (PH) nalazom potvrdjen je nalaz skvamozne interepitelne lezije niskog stepena (LSIL) kod 38% ispitanica i nalaz skvamozne intraepitelne lezije visokog stepena (HSIL) kod 69,2% (p > 0,05). Korelacijom p16 testa sa PH nalazom utvrdjena je statisticka znacajna pozitivna korelacija izmedju pozitivnosti p16 testa i stepena lezije (p = 0,000). Nalaz p16 bio je pozitivan kod 70% bolesnica sa LSIL i 94,4% sa HSIL promenama. Analizom vrednosti p16 testa prema Papanikolau testu utvrdjeno je postojanje pozitivne korelacije izmedju pozitivnosti p16 testa i stepena lezije (p = 0,011). Nalaz p16 bio je negativan kod 38% bolesnica sa LSIL i 15% sa HSIL promenama. Tipizacijom HPV utvrdjen je kao najzastupljeniji pozitivan nalaz na HPV 16. Analizom rezultata p16 testa prema HPV statusu i Papanikolau testa prema HPV statusu dobijeni su heterogeni rezultati. Zakljucak. Kod bolesnica sa premalignim lezijama grlica materice postoji znacajnija pozitivna korelacija stepena ekspresije p16INK4a proteina u razmazu citoloskog brisa grlica materice sa stepenom histoloske displazije, u odnosu na nalaz Papanikolau testa.