CYTOMORPHOLOGIC ABNORMALITIES OF THE SQUAMOUS EPITHELIUM AND HIGH-RISK HPV IN CERVICAL SMEARS PROCESSED BY LIQUID BASED CYTOLOGY (LBC)

Cilj istraživanja: Odrediti udio pojedinih citoloških dijagnoza nakon morfološke analize uzoraka grlića maternice uzetih metodom tekućinske citologije (LBC), odrediti udio uzoraka koji su molekularnom analizom pozitivni na HPV visokog rizika te utvrditi valjanost citološke analize i citomorfoloških promjena vezanih uz HPV infekciju u odnosu na HPV tipizaciju. Ispitanici i metode: Retrospektivno istraživanje obuhvatilo je 330 ispitanica čiji su uzorci nakon citomorfološke analize poslani na molekularnu analizu (HPV tipizaciju) u Laboratorij za kliničku i sudsku genetiku Kliničkog zavoda za patologiju, sudsku medicinu i citologiju. U istraživanje su uključeni uzorci briseva grlića maternice obrađenih metodom tekućinske citologije (LBC), zaprimljeni s Klinike za ženske bolesti i porode KBC Split te iz ginekoloških ordinacija na području Splitsko-dalmatinske županije, u razdoblju od 2010. do 2013. godine. Medijan životne dobi ispitanica uključenih u istraživanje iznosio je 41 godinu (min-max, 21-82 god.). Rezultati: Od ukupnog broja ispitanica koje su HPV negativne po tipizaciji i nemaju morfološke promjene na stanicama vezane uz HPV (N=132), uredan citološki nalaz prisutan je u 106 (80%) ispitanica. U ovoj skupini, u 14 (11%) ispitanica citološkom analizom nađene su atipične stanice, dok je u njih 12 (9%) postavljena citološka dijagnoza CIN I. Od 71 ispitanice koje nemaju morfološke promjene na stanicama vezane uz HPV, ali im je molekularnom analizom identificiran HPV visokog rizika, u 8 (11%) ispitanica je citološkom analizom postavljena dijagnoza atipičnih stanica, u 7 (10%) CIN I, u jedne (1%) CIN II, dok je u njih 55 (78%) citološki nalaz je bio uredan. U svih ispitanica (N=9) koje su po tipizaciji HPV negativne, ali imaju izražene morfološke promjene na stanicama vezane uz HPV, postavljena je citološka dijagnoza CIN I. Sve ispitanice koje su po tipizaciji HPV pozitivne i imaju izražene morfološke promjene na stanicama vezane uz HPV (N=106) imaju pozitivan citološki nalaz; 8 (8%) atipične stanice, 61 (58%) CIN I, 22 (21%) CIN II i 15 (14%) CIN III. Zaključci: Povezanost između citomorfoloških promjena vezanih uz HPV infekciju i HPV tipizacije nije dovoljno statistički značajna da bi samo citomorfološka analiza mogla pouzdano otkriti HPV infekciju. Dobiveni rezultati analize pokazuju da citomorfološki znakovi HPV infekcije imaju ograničenu vrijednost u predviđanju rezultata HPV tipizacije, uz osjetljivost metode od 60.4%, ali specifičnost od 89.8%. U skupini ispitanica s urednim citološkim nalazom kod 34% ispitanica tipizacijom je dokazana infekcija HPV–om visokog rizika. Ove ispitanice spadaju u izrazito rizičnu skupinu jer su neprepoznate samom morfološkom analizom te stoga ne ulaze u algoritam češćeg praćenja i daljnje obrade.Aims of the study: To determine the specific cytologic diagnosis after morphological analysis of samples taken from the cervix by liquid based cytology (LBC); to determine the proportion of samples that are positive for high-risk HPV by molecular analysis; to determine the validity of the cytological analysis and cytomorphological changes associated with HPV infection compared to the HPV typing. Methods: This study included 330 women whose samples after cytological analysis were sent for molecular analysis (HPV typing) to the Laboratory for Clinical and Forensic Genetics, Clinical Institute of Pathology, Forensic Medicine and Cytology. The study involved samples of cervical smears processed by liquid based cytology (LBC), received from the Department of Gynecology and Obstetrics, Clinical Hospital Center Split, and from the gynecological clinics in Split-Dalmatia County, in the period from 2010. to 2013. The median age of women included in the study was 41 years (min-max, 21-82 yr.). Results: Of the total number of women who were negative by HPV typing and without cytomorphologicalchanges associated with HPV (N=132), regular/negative cytology findings were present in 106 (80%) women. In this group, in 14 (11%) cases atypical cells were found by cytological analysis, whereas in 12 cases (9%) CIN I was diagnosed. Of 71 women who had no morphological changes in cells associated with HPV, but their molecular analysis identified high-risk HPV, in 8 women (11%) cytological diagnosis was of atypical cells, in 7 cases (10%) CIN I, in one case (1%) CIN II, while in 55 cases (78%) cytology was normal. In all women (N=9) who were HPV negative on molecular analysis, but with marked cytomorphological changes associated with HPV, on cytological analysis CINI was diagnosed. All women (N=106) who were HPV positive on molecular analysis and had marked cytomorphological changes associated with the HPV, had positive cytological results: 8 (8%) had findings of atypical cells, 61 (58%) of CIN I, 22 (21%) of CIN II and 15 (14%) of CINIII. Conclusion: The association between cytomorphological changes associated with HPV infection and HPV typing is not significant enough to just cytomorphological analysis could reliable detect HPV infection. The results of the analysis show that cytomorphological signs of HPV infection have only limited value in predicting the results of HPV typing, with the normal cytological results (161 subjects), in 55 women (34%) molecular analysis revealed high risk HPV. These women are high-risk group because they are unrecognized on the morphological analysis and therefore not included in the algorithm for more frequent monitoring and further treatment