Human papillomavirus and cervical cancer: mechanisms of carcinogenesis, epidemiology, diagnostics and prophylaxis

Abstract

Infekcija humanim papiloma virusom (HPV) najčešća je spolno prenosiva bolest i pretpostavlja se da genitalnu infekciju ovim virusom ti jekom života stekne 75 – 80 % spolno aktivnih žena i muškaraca. Od ranih osamdeseti h kada je Harald zur Hausen (dobitnik Nobelove nagrade za fiziologiju ili medicinu 2008. godine) dokazao humani papiloma virus (HPV) genotipa 16 i 18 u karcinomu cerviksa, u velikom broju studija potvrđeno je i znanstvenim činjenicama dokazano da je infekcija HPV-om ključni čimbenik u razvoju karcinoma cerviksa. Maligne promjene cerviksa nastaju ako su ispunjeni višestruki uvjeti koji su defi nirani virusnim značajkama, staničnim protuvirusnim mehanizmima i imunim odgovorom domaćina. Virusnu komponentu čine genoti p virusa, perzistencija i intenzitet infekcije, a imunogenetička konstitucija pojedinca, stanično posredovani imuni odgovor i utjecaj vanjskih čimbenika kao što su lijekovi i bolesti, definiraju imunopatogenetski doprinos domaćina. Ključni proteini uključeni u nastanak karcinoma cerviksa su virusni onkogeni, E6 i E7, koji interferiraju s nizom staničnih procesa te dovode do nekontrolirane proliferacije i stanične imortalizacije, stoga je značaj molekularnih studija koje se bave problematikom HPV-a upravo u boljem razumijevanju patogeneze HPV-a te primjeni stečenih spoznaja u prevenciji virusne infekcije, razvoju profilaktičkog cjepiva i uvođenju molekularne dijagnosti ke kao standarda u procjeni rizika za žene izložene kroničnoj infekciji HPV-om.Human papillomavirus (HPV) infecti on is esti mated to be the most common sexually transmitt ed disease and about 75-80% of sexually active men and women will be infected with HPV at some point in their lifeti me. Since the early 1980s when Harald zur Hausen (winner of the Nobel Prize in 2008 for Physiology or Medicine) detected the HPV genotypes 16 and 18 in cervical cancer, a large number of studies have provided scienti fi c evidence that HPV infection is a key factor in the development of cervical carcinoma. Malignant changes of the cervix occur if multiple conditions are met and they are defined by virus characteristics, anti viral mechanisms and by the cellular immune response of the host. Viral components important in carcinogenesis are viral genotype, intensity and persistence of the infecti on, while immunogenetic constitution of the individual, cell mediated immune responses and influence of the external factors such as drugs and diseases defi ne immunopathogenetic contributi on of the host. Key proteins involved in the development of cervical cancer are viral oncogenes, E6 and E7, which interfere with a variety of cellular processes and lead to uncontrolled cell proliferati on and immortalisation. Therefore, the importance of molecular studies dealing with HPV lies in the fact that they enable us to better understand the HPV pathogenesis and facilitate application of the acquired knowledge in the preventi on of HPV infections, development of prophylactic vaccines and introducti on of molecular diagnosti cs as a standard in the risk assessment for women exposed to the chronic HPV infection