title: Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer.
abstract: Human papillomavirus type 16 (HPV-16) classes (E, AA, As, Af1, Af2) and their variants have different geographic distribution and different degrees of association with cervical lesions. This study was designed to examine HPV-16 variants among Italian women and their prevalence in case patients (affected by invasive cervical carcinoma or cervical intraepithelial neoplasia grade 2-3 and cervical intraepithelial neoplasia grade 1), versus control subjects with normal cervical epithelium (controls). A total of 90 HPV-16 positive cervical samples from women of Italian Caucasian descent have been tested, including 36 invasive cervical carcinomas, 21 with cervical intraepithelial neoplasias grade 2-3, 17 with cervical intraepithelial neoplasia grade 1 and 16 controls. HPV-16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV-16 classes and subclasses were identified by direct nucleotide sequencing of the region coding for the E6 and the E7 oncoproteins, the MY09/11-amplified highly conserved L1 region, and the long control region (LCR). Among the 90 HPV-16 samples, nine viral variants have been identified belonging to the European (Ep-T350 and E-G350) and non-European (AA and Af-1) branches. The E-G350 is the prevalent variant in all analyzed different disease stages being present in 55.5% of ICC, 52.4% of cervical intraepithelial neoplasias 2-3, 47.1% of cervical intraepithelial neoplasia grade 1, and 50.0% of control samples. The non-European variants AA and Af1, rarely detected in control samples, represent 33.3% of all HPV-16 infections in invasive cervical carcinoma (with a peak of 19.4% and 13.9%, respectively), showing a statistically significant increase in frequency in more advanced lesions (chi(2) trend = 7.2; P < 0.05). The prevalence of HPV-16 Ep-T350, however, is higher in controls (43.7%) and in of cervical intraepithelial neoplasia grade 1 (41.2%) than in cervical intraepithelial neoplasia grade 2-3 (28.6%) and in invasive cervical carcinoma (11.1%) cases strongly suggesting lack of progression for pre-neoplastic lesions associated with such variant. The increased frequency of non-European variants in invasive lesions suggests that they are more oncogenic than European variants. This could have implications for future diagnostic and therapeutic strategies.
authors.affiliation: Viral Oncology and AIDS Reference Centre, National Cancer Institute, Fond. Pascale, Naples, Italy.
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Tornesello
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Duraturo
authors.forename: Immacolata
authors.initials: I
authors.lastname: Salatiello
authors.forename: Luigi
authors.initials: L
authors.lastname: Buonaguro
authors.forename: Simona
authors.initials: S
authors.lastname: Losito
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stellato
authors.forename: Stefano
authors.initials: S
authors.lastname: Greggi
authors.forename: Roberto
authors.initials: R
authors.lastname: Piccoli
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Bernardina
authors.initials: B
authors.lastname: Stefanon
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palo
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschi
authors.forename: Franco M
authors.initials: FM
authors.lastname: Buonaguro
mesh_terms: D000328:Adult; D000368:Aged; D036022:Capsid Proteins / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005814:Genes, Viral; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D017720:Molecular Epidemiology; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology*
chemical_list: D036022:Capsid Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C063317:L1 protein, Human papillomavirus type 16