Onkogeneza povezana s HPV-om u tumorima glave i vrata

Vjekoslav Tomaić, Nina Milutin Gašperov, Ivan Sabol, Magdalena Grce

Više od 200 papilomavirusa čovjeka (HPV) inficira stanice ljudskog epitela, od kojih su alfa i beta tipovi najopsežnije proučavani i analizirani. Alfa-tipovi HPV-a primarno inficiraju epitel sluznice, a samo manji njihov dio povezan je s više od 600.000 karcinoma godišnje širom svijeta na različitim anatomskim mjestima, posebno anogenitalnim i regijama glave i vrata. Najvažniji karcinom uzrokovan alfa-tipovima HPV-a jest rak vrata maternice, koji je vodeći uzrok smrti povezane s rakom kod žena u mnogim dijelovima svijeta. HPV kodiraju dva onkoproteina, E6 i E7, koji izravno sudjeluju u razvoju malignosti povezanih s HPV-om. Oni djeluju u sinergiji, ciljajući različite stanične puteve koji su uključeni u regulaciju kontrole staničnog ciklusa, apoptoze i polariteta stanica. U ovom su pregledu istaknute biološke posljedice papilomavirusa koji djeluju na različite stanične proteine na različitim anatomskim mjestima u razvoju malignih tumora izazvanih HPV-om, s naglaskom na tumore glave i vrata.

More than 200 human papillomaviruses (HPVs) infect human epithelial cells, and out of them alpha and beta types have been the most extensively investigated and analysed. Alpha HPVs primarily infect mucosal epithelia and only a small proportion of them is associated with more than 600,000 cancers per year worldwide at various anatomical sites, especially anogenital and head-and-neck region. Of these the central disease is cervical cancer, which is the leading cause of cancer-related deaths in women in numerous parts of the world. HPVs encode two oncoproteins, E6 and E7, which are directly involved in the development of HPV-mediated malignancies. They do this in cooperation by targeting various cellular pathways involved in the regulation of cell cycle control, of apoptosis and of cell polarity control networks. In this review, the biological consequences of HPV manipulating of various cellular proteins at diverse anatomical sites in the development of HPV-induced carcinogenesis are depicted, with focus on head and neck cancer.