The role of human papillomavirus (hpv) in the development of benign and malignant changes of the oral mucosa

doctoral thesis

• Title (croatian): Uloga humanih papiloma virusa (hpv) u razvoju dobroćudnih i zloćudnih promjena sluznice usne šupljine
• Author: Marjana Knežević
• Mentor: Marinka Mravak-Stipetić (mentor)
• Mentor: Magdalena Grce (komentor)
• Committee member: Vlaho Brailo (predsjednik povjerenstva)
• Committee member: Irina Filipović Zore (član povjerenstva)
• Committee member: Romana Čeović (član povjerenstva)
• Committee member: Krunoslav Kuna (član povjerenstva)
• Committee member: Ivan Alajbeg (član povjerenstva)
• Granter: University of Zagreb; School of Dental Medicine; (Department of Oral Medicine); Zagreb
• Defense date and country: 2017-03-06, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Dental Medicine; Oral Medicine
• Universal decimal classification (UDC): 616.31 - Stomatology

Abstract

Objectives: The aim of this study was to determine the prevalence and type of human papillomavirus (HPV) in various oral lesions in comparison to control healthy oral mucosa, and the dynamic of HPV infection course (persistence, change of HPV type and clearance).
Material and Methods: The study comprised 426 consented subjects, of which 343 patients with different oral lesions and 83 controls with apparently healthy oral mucosa, referred for oral examination in the period from 2000 to 2015. The diagnoses of oral lesions were established according to clinical criteria and confirmed by histopathology. Oral cytobrush samples were collected from oral lesions and healthy mucosa from different topographic sites and the HPV types were determined by polymerase chain reaction (PCR). The presence of HPV DNA was evaluated by consensus and type-specific (TS) primer-directed PCR. A subset of samples was analysed for the presence of both alpha and beta genus HPV types.
Results: Out of 426 specimens, 144 (41.98%) from oral lesions and 15 (18.07%) controls were positive for HPV DNA; 22.3% of all tested samples contained beta-HPV type and 15.02% alpha-PV type. The highest prevalence of beta-HPV and high risk (HR) HPV (alpha-HPV) types were found in benign and premalignant oral lesions, while HR-HPVs were found in a small number of control samples. In 38 subjects sampling was performed more than twice, in average 2.29 times, with time distance between sampling of 5.8 months. Twenty-six of these 38 patients were continuously HPV negative, five had transient infection, five acquired a new HPV infection, one had persistent HPV infection, and one had initially co-infection with different HPV types followed with new one during which initial oral lesion became malignant. The topographic distribution of the alpha-PV and beta-PV types showed affinity for the anterior part of the oral cavity and particular risk localization.
Conclusion: Positive finding of HPV in all age groups and on healthy oral mucosa, high prevalence of HPV types in oral premalignant and proliferative lesions, affinity for risk localization in the oral cavity, unpredictable dynamic course and change of HPV type indicates the need for regular oral assessment and HPV control in patients with initially positive findings on oral mucosa.

Abstract (croatian)

Cilj istraživanja bio je ispitati prevalenciju i tip humanog papiloma virusa (HPV) u različitim oralnim lezijama u usporedbi s kontrolnom, naizgled zdravom sluznicom i dinamiku tijeka HPV infekcije u ustima (ustrajnost, promjenu tipa HPV i prolaznost infekcije).
Ispitanici i postupci: U ispitivanju je sudjelovalo 426 ispitanika, od kojih 343 bolesnika s različitim oralnim lezijama i 83 kontrolnih s naizgled zdravom sluznicom koji su upućeni na pregled usne šupljine u razdoblju od 2000. do 2015.godine. Svi ispitanici dali su svoj informirani pristanak prije uključivanja u ovo istraživanje. Dijagnoze oralnih lezija postavljene su na temelju kliničkih kriterija i potvrđene histopatološkom analizom. Citološki obrisci uzeti su citološkom četkicom s oralnih lezija i zdrave sluznice s topografski različitih mjesta sluznice, a HPV je dokazan lančanom reakcijom polimerazom (PCR). Prisutnost HPV DNA dokazana je PCR-om sa zajedničkim i tip-specifičnim početnicama. Određeni dio uzoraka bio je testiran na tipove HPV-a iz roda alfa i beta.
Rezultati: U svih 426 testiranih uzoraka, HPV DNA dokazana je u 144 (41,98%) uzoraka s oralnih lezija i 15 (18,07%) kontrolnih; 22,3% ispitanih uzoraka sadržavalo je tip HPV iz roda beta, a 15,02% tip HPV iz roda alfa. Najveća prevalencija beta-HPV i visokorizičnih (HR) HPV tipova (alfa-HPV) pronađeni su u benignim i premalignim oralnim lezijama, a visokorizični HPV tipovi pronađeni su i u malom broju kontrolnih uzoraka. U 38 ispitanika uzorkovanje je provedeno više od dva puta, u prosjeku 2.29 puta, u vremenskom razmaku od prosječno 5,8 mjeseci. Dvadesetšest od 38 ispitanika bilo je stalno negativno na HPV, u pet je dokazana prolazna infekcija, pet je steklo novu infekciju HPV-om, jedan ispitanik imao je stalnu infekciju HPV-om, a jedan je tijekom praćenja početno dokazanu koinfekciju s različitim tipovima HPV-a i stekao novu s HPV tipom visokog rizika tijekom koje je inicijalna premaligna lezija sluznice postala zloćudna. Analiza topografske distribucije alfa-HPV i beta-HPV tipova na oralnoj sluznici pokazala je afinitet virusa za sluznicu prednjeg dijela usne šupljine i osobito za rizične lokalizacije.
Zaključak: Pozitivan nalaz HPV-a u svim dobnim skupinama i na zdravoj sluznici te visoka prevalencija HPV tipova u oralnim premalignim i proliferativnim lezijama kao i afinitet za rizične lokalizacije te nepredvidljiv dinamičan tijek uz promjene tipa HPV-a upućuju na potrebu kontrole na HPV u kliničkoj stomatološkoj praksi kod inicijalno pozitivnog nalaza.

• Keywords: oral cavity; benign oral lesions; premalignant oral disorders; oral cancer; human papillomaviruses (HPV); alpha-PV type; beta-PV type
• Keywords (croatian): usna šupljina; dobroćudne oralne lezije; premaligne lezije; rak usne šupljine; humani papilomavirusi (HPV); alfa-HPV; beta-HPV
• Language: english
• URN:NBN: urn:nbn:hr:127:980851
• Study programme: Title: dental medicine; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo, polje dentalna medicina (doktor/doktorica znanosti, područje biomedicine i zdravstvo, polje dentalna medicina)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-01-11 11:31:09