Comparison of cytological and histopathological findings in patients with cervical dysplasia

Citološki probir ranog otkrivanja raka vrata maternice i intraepitelnih promjena značajno je smanjio morbiditet i mortalitet od ove bolesti zadnjih 50-ak godina širom svijeta, a naročito u razvijenim zemljama koje već desetljećima provode sustavni nacionalni probir i imaju dostupne nacionalne baze podataka prethodnih citoloških, kolposkopskih, mikrobioloških i patohistoloških nalaza. Najvažniji cilj probira je otkrivanje rizične populacije prije nastanka invazivne bolesti kako bi liječenje bilo što manje invazivno. To je posebno važno zbog činjenice da često obolijevaju žene reproduktivne dobi koje još planiraju trudnoću. Boljim razumijevanjem karcinogeneze i uloge infekcije humanim papiloma virusom visokog rizika (hrHPV) razvijeni su komercijalni testovi za otkrivanje ove infekcije i prije razvoja epitelnih promjena. Hrvatski nacionalni program ranog citološkog otkrivanja raka vrata maternice i intraepitelnih promjena pokrenut je 2012. godine, ali se zbog određenih nedostataka trenutno revidira. Trenutni prijedlog pilot programa predviđa citološki probir žena dobne skupine 20-29 godina, kotestiranje citologijom i hrHPV testom žena 30-34 godine te primarno hrHPV testiranje žena 35-65 godine života. Cilj ovog rada je doprinijeti izboru najbolje opcije za rani probir raka vrata maternice u Hrvatskoj, kao i preinvazivnih promjena. ----- MATERIJALI I METODE: U ovom retrospektivnom istraživanju analizirali smo dostupne podatke iz bolničkog informatičkog sustava (BIS) za žene kojima je tijekom 2017. godine, u našem patohistološkom laboratoriju, rađena analiza promjena vrata maternice. Izdvojeno je 128 žena s patohistološkom dijagnozom HSIL i dostupnim prethodnim nalazima citologije i hrHPV testiranja. ----- REZULTATI: Prosječna dob žena bila je 44.7 godina s rasponom od 21 do 77 godina. Za 76 bolesnica s dijagnozom HSIL na konusu prosječna dob je bila 39.7, a za skupinu od 8 bolesnica s mikroinvazivnim i invazivnim karcinomom prosječna dob bila je 44 godine. Kod 76 bolesnica s PHD nalazom HSIL na konusu, PAPA nalazi prije konizacije su bili HSIL/ASC-H 87% (66/76), CIS/CIN 7.8% (6/76), Ca planocelullare rana invazija 1.3% (1/76), AGC-NOS 1.3 (1/76). U dva slučaja PAPA nalaz je bio LSIL – 2.6%. Nije bilo citološki negativnih nalaza u obje skupine (LSIL i HSIL). Kod 13 bolesnica s planocelularnim karcinomom cerviksa, FIGO I A1 i FIGO I A2 i s adenokarcinomom, PAPA test prije zahvata je ukazivao na visoki stupanj preinvazivnih, i sumnje na invazivni zloćudni tumor vrata maternice. Kod 19% bolesnica kod kojih je konačni PHD nalaz bio HSIL, prethodna biopsija je bila negativna. Analizirajući hrHPV nalaze, oni su bili pozitivni u 80% bolesnica s HSIL na konusu. Analizom konusa prema tipu operacije vidljivo je da je neadekvatan nakon LETZ konizacije bio kod 62% bolesnica, a kod konizacije nožem u 29% bolesnica. ----- ZAKLJUČAK: Citologija je prepoznata kao dobra metoda probira raka vrata maternice, posebno u Hrvatskoj gdje je ta grana medicine vrlo razvijena. Prikazani rezultati potvrđuju pouzdanost i dijagnostičku točnost ove metode naročito kod HSIL promjena vrata maternice. Prije prijelaza na primarni hrHPV probir, trebalo bi napraviti dobro definiranu pilot studiju koja uključuje kotestiranje, i razmotriti koja metoda hrHPV tipizacije bi se uključila u primarni probir jer različite metode u različitim sredinama nemaju iste rezultate. HrHPV negativni slučajevi HSIL-a opisani su u brojnim radovima u literaturi, a najčešće se objašnjavanju kao: neadekvatno uzet uzorak za tipizaciju, malen broj čestica virusa u uzorku, onečišćenje uzorka tvarima koje ometaju analizu, kao i malom broju zaista hrHPV negativnih slučajeva.The early screening for cervical cancer and intraepithelial changes significantly reduced the morbidity and mortality of this disease in the last 50 years, especially in developed countries that have implemented systematic national screening and have available national databases of previous cystological, colposcopic, microbiological and pathohistological findings. The most important aim of the screening is to determine the risk population prior to the onset of invasive disease in order, to make the treatment less invasive. This is especially important due to the fact that the most common patients are women of childbearing potential. Better understanding of carcinogenesis and the role of high-risk Human papillomavirus (hrHPV) infection has developed tests to detect this infection before the development of epithelial lesions. The first organised national cytology screening program for detecting cervical cancer and intraepithelial lesions in Croatia was initiated in 2012, but due to the certain shortcomings, it is currently under revision. The working proposal of the program is to screen women aged 20-29 by cytology alone, the cytology and high-risk HPV test for women age group 30-34, and primarily high-risk HPV testing for women 35-65 years old. The aim of this study is to help to choose the best option for early screening of cervical cancer, and preinvasive lesions in Croatia. ----- SAMPLE AND METHODS: In this retrospective study, we have analyzed available information from the Hospital Information System (BIS) for women who, during the year 2017, underwent our analysis of cervical changes. 128 women with histopathological diagnosis of HSIL and available previous cytology and hrHPV testing were selected. ----- RESULTS: The average age of women was 44.7 years, ranging from 21 to 77 years. For 76 patients with HSIL diagnosis, the average age was 39.7, and for the group of 8 patients with microinvasive and invasive cancer the average age was 44 years. In 76 patients HSIL on the PHD was found, and the PAPA-test findings prior to the conisation were HSIL/ASC-H 87% (66/76), CIS/CIN 7.8% (6/76), early invasion of planocellular carcinoma 1.3% (1/76), AGC-NOS 1.3 (1/76). In two cases PAPA was found to be LSIL - 2.6%. There were no cytological negative findings in either of these two groups (LSIL and HSIL). In 13 patients with planocellular carcinoma of the cervix, FIGO I A1 and FIGO I A2 and with adenocarcinoma, the PAPA test prior to the procedure indicated a high degree of preinvasive and suspected invasive malignant tumor of the cervix. In 19% of patients with final PHD findings of HSIL, the previous biopsy was negative. Detecting high-risk HPV was positive in 80% of patients with HSIL at the cone. The analysis of the cones showed that the sample was inadequatly taken after LETZ-conization in 62% of the patients, and in the conization with a knife in 29%. ----- CONCLUSION: Cytologic evaluation has been recognized as a good method for cervical cancer screening, especially in Croatia where this branch of medicine is very developed. The results presented confirm the reliability and diagnostic accuracy of this method, especially in HSIL cervical occlusion. Prior to the transition to the primary hrHPV screening, a well-defined pilot study should be conducted because different methods in different environments do not have the same results. hrHPV negative cases of HSIL have been described in many papers, and most often explained as: inadequate sampling, small number of virus particles in the sample, or sample contamination by substances that interfere with the analysis