Ploidnost tumorskih stanica i tip humanog papiloma virusa u cervikalnim intraepitelnim neoplazijama

Župić, Tomislav (2011) Ploidnost tumorskih stanica i tip humanog papiloma virusa u cervikalnim intraepitelnim neoplazijama. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Research goals: It is an attempt to discover the relationship between HPV type and cell ploidy in high grade CIN in its progression to invasive cervical cancer and to detect the fraction of the patients who do not need urgent conization. ----- Examinees and methods: Hysterectomy or conization was done in 147 patients with the diagnosis of high grade CIN on the biopsy. Patohystological analysis, PCR and flow citometry of the DNA was done on the obtained specimen. ----- Results: Patient age positively correlates with higher grade of CIN, from CIN I to MIC (p < 0,01). 168 HPV types was detected; 67.3% of HR, 8.9% of LR and 23.8% of unknown oncogenic risk type. The most common was HPV type 16 in 47% samples and in 13.6% samples we found infection with multiple HPV types. Higher CIN negatively correlates with HPV types 6 and 11 (p < 0,01) (never aneuploid) and positive correlates with HPV type 18 (p < 0,05) (always aneuploid). Correlation between higher CIN and other HPV types was not established. HPV types 6 and 11 was not solely found in MIC but it was found solely in 2.5% of the patients with CIN III. In all samples we detected 58.5% diploidy, 33.3% aneuploidy and 8.2% tetraploidy. We found correlation of aneuploidy with higher grade of the disease - 0% CIN I; 18,9% CIN II; 50% CIN III; 71% MIC (p < 0,001). We found statistically significant correlation between high risk HPV types (16, 31 and 33) and frequency of aneuploidity in patients with higher grade CIN. ----- Conclusion: It is not necessary to routinely detect HPV types (it is enough to establish high risk HPV group) or ploidity of the tumor cells in CIN. If the patient with CIN II/III desires fertility and insists on conservative approach (follow up without immediate conization), HPV type can be detected. If HPV types 6 and 11 was detected, patient can be only closely followed; in the case of HPV type 18 we should proceed with the treatment and if HPV types 16, 31 or 33 are detected, ploidity of the tumor cells should be assessed and if the tumor cells are diploid, close follow up is warranted.

Abstract in Croatian

Ciljevi istraživanja: Pokušati otkriti ulogu i međusobnu vezu tipa HPV-a i ploidnosti stanica u CIN-u visokog stupnja (CIN II i CIN III) u njegovoj progresiji u invazivni rak vrata maternice te izdvojiti skupinu bolesnica kod kojih nije potrebna žurna konizacija. ----- Ispitanice i metode: U 147 bolesnica s dijagnozom CIN-a visokog stupnja (CIN II i CIN III) na biopsiji vrata maternice učinjena je konizacija ili histerektomija. Dobiveni materijali pregledani su patohistološki, učinjena je PCR i analiza sadržaja DNA protočnom citometrijom. ----- Rezultati: Dob bolesnica je pozitivno korelirala s porastom stupnja epitelne promjene od CIN-a I do MIC-a (p < 0,001). Ukupno je nađeno 168 tipova HPV-a: 67,3% visokog rizika, 8,9% niskog rizika i 23,8% tipova nepoznatog rizika onkogenosti. HPV tip 16 je najčešći izolirani virus (47%), a istodobna višestruka zaraza tipova HPV-a nađena je u 13,6% uzoraka (NS). Prema težini patohistološke dijagnoze pronađena je negativna povezanost za HPV tipove 6 i 11 (p < 0,01) (nikad aneuploidni) i pozitivna povezanost za HPV tip 18 (p < 0,05) (uvijek aneuploidni), a za ostale tipove HPV-a nije nađena (NS). U MIC-u se nikada ne nalaze samostalno HPV tipovi 6 i 11, ali se nalaze u 2,5% bolesnica s CIN-om III. Nađeno je 58,5% diploidnih, 33,3% aneuploidnih i 8,2% tetraploidnih uzoraka. Nađena je povezanost aneuploidnosti s porastom težine dijagnoze – 0% za CIN I; 18,9% za CIN II; 50% za CIN III i 71% za MIC (p < 0,001). Kod zaraze tipovima HPV-a visokog rizika (16, 31 i 33) raste učestalost aneuploidnosti prema težini dijagnoze sa statistički značajnom povezanosti. ----- Zaključak: U cervikalnim intraepitelnim neoplazijama nije potrebno rutinski određivati tipove HPV-a (osim skupine HPV-a visokog rizika) i ploidnost tumorskih stanica. Tipizacija HPV-a opravdana je u bolesnica s CIN-om II ili III koje žele zanijeti, zbog mogučnosti poštednog pristupa (praćenje bez žurne konizacije). Uz nalaz HPV tipova 6 i 11 bolesnicu je moguće samo pratiti, u slučaju nalaza HPV tipa 18 potrebno je učiniti zahvat, a kod nalaza HPV tipova 16, 31 i 33 treba odrediti ploidnost tumorskih stanica jer diploidnost ukazuje na sporiju progresiju promjene, što omogućuje kliničko praćenje.

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