title: Signature patterns of human papillomavirus type 16 in invasive anal carcinoma.
abstract: Many studies have reported that most invasive anal carcinomas contain high-risk human papillomaviruses (HPVs), HPV16 being the most prevalent type. This study aimed to investigate HPV status and cellular biomarkers in invasive anal cancers. HPV genotype distribution was determined in 76 anal cancers by the INNO-LiPA assay (Innogenetics, Gent, Belgium). HPV16-positive samples were then tested for viral load and physical state with type-specific real-time polymerase chain reaction targeting E6, E2, and albumin genes. Samples were also subjected to immunohistochemical analysis of p16, Ki-67, p53, and p21. Of the analyzable tumors, 98.6% were positive for α-HPV DNA. HPV16 was the most prevalent genotype (89.0%), followed by HPV39 (4.1%) and HPV33 (2.7%). HPV16 viral load was high, ranging from 2.1 × 10(3) to 1.5 × 10(7) copies/10(3) cells. Integration of HPV16 estimated by the E2/E6 ratio was detected in 77.8% of cases, among which 70.4% were mixed integrated and episomal DNA cases and 7.4% were fully integrated DNA cases. The latter cases were associated with a low HPV16 load compared with cases containing either episomes or mixed integrated and episomal DNA. As expected, most HPV16-positive tumors expressed p16 (92.6%) with a high proliferative index, whereas a minority of them overexpressed p53 (10.3%). p21 expression did not appear to correlate with p53 expression. Although HPV16 was almost exclusively detected, high viral load and differences in DNA integration have been identified in the present series of anal cancers. HPV features assessed in conjunction with expression of cell-cycle regulators could be helpful, as joint biomarkers, in predicting clinical outcome.
authors.affiliation: Univ Franche-Comte, F-25000 Besancon, France. svalmary@univ-fcomte.fr
authors.forename: Séverine
authors.initials: S
authors.lastname: Valmary-Degano
authors.forename: Elise
authors.initials: E
authors.lastname: Jacquin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Prétet
authors.forename: Franck
authors.initials: F
authors.lastname: Monnien
authors.forename: Benoit
authors.initials: B
authors.lastname: Girardo
authors.forename: Francine
authors.initials: F
authors.lastname: Arbez-Gindre
authors.forename: Marie
authors.initials: M
authors.lastname: Joly
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bosset
authors.forename: Bernadette
authors.initials: B
authors.lastname: Kantelip
authors.forename: Christiane
authors.initials: C
authors.lastname: Mougin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000473:pathology / Q000821:virology*; D002277:Carcinoma / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D015995:Prevalence; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D004279:DNA, Viral