title: Double demonstration of oncogenic high risk human papilloma virus DNA and HPV-E7 protein in oral cancers.
abstract: Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.
authors.affiliation: Department of Surgical Sciences, Section of Anatomic Pathology and Cytopathology, University of Foggia, Foggia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pannone
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: F
authors.initials: F
authors.lastname: Carinci
authors.forename: P
authors.initials: P
authors.lastname: Bufo
authors.forename: S M
authors.initials: SM
authors.lastname: Papagerakis
authors.forename: C
authors.initials: C
authors.lastname: Rubini
authors.forename: G
authors.initials: G
authors.lastname: Campisi
authors.forename: L
authors.initials: L
authors.lastname: Giovannelli
authors.forename: M
authors.initials: M
authors.lastname: Contaldo
authors.forename: R
authors.initials: R
authors.lastname: Serpico
authors.forename: M
authors.initials: M
authors.lastname: Mazzotta
authors.forename: L
authors.initials: L
authors.lastname: Lo Muzio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics / Q000821:virology*
chemical_list: D004279:DNA, Viral; D050725:Papillomavirus E7 Proteins