title: HIV positivity but not HPV/p16 status is associated with higher recurrence rate in anal cancer.
abstract: OBJECTIVE
  Human papillomavirus (HPV) is a pathogenic factor of squamous cell carcinoma in various mucosal locations, including anal carcinoma (ACA). It is also known that patients positive for HIV are at high risk of ACA. The goal of this study was to examine clinical outcome in ACA in relation to HPV/p16 positivity, histologic tumor differentiation, and HIV status. Patients with oropharyngeal cancers that are positive for HPV and show overexpression of p16 as well as having non-keratinizing/basaloid histology have been reported to have better outcomes following chemoradiation (CRT). However, such relationships in ACA remain unknown.
  
  
  METHODS
  Forty-two patients with SCC of the anus treated with CRT between 1997 and 2009 were identified. The tumors were subclassified as either non-keratinizing (including basaloid) or keratinizing categories. HPV testing was performed using SPF10-PCR, and all cases were immunostained for p16.
  
  
  RESULTS
  There were 23 men and 19 women; 43% of men and 11% of women were HIV-positive (p = 0.04). Fifty-five percent of patients had local disease (stages I and II) and 41% were stages III and IV, with 4% stage unknown. All tumors were positive for high-oncogenic risk HPVs, and all were positive with p16 immunostain. Sixty-four percent of tumors were non-keratinizing/basaloid and 36 % were keratinizing. The keratinizing tumors were more common in HIV-positive patients (67%), whereas non-keratinizing/basaloid tumors were more common in HIV-negative patients (77%) (p = 0.008). Thirty-one percent of patients had recurrence of disease, including 50% HIV-positive patients and 23% HIV-negative patients (p = 0.09). There was no difference in the recurrence rate between non-keratinizing and keratinizing tumor subtypes (p = 0.80). The 24-month recurrence-free survival for the cohort was 66% (95% CI = 46%, 81%), with HIV-positive patients having worse recurrence-free survival compared to HIV-negative patients (HR = 2.85, 95% CI = 0.95, 8.53; p = 0.06).
  
  
  CONCLUSIONS
  The regional and distant failure rate was not related to HPV/p16 positivity or histologic differentiation of ACA; however, HIV positivity appeared to be associated with a higher recurrence rate and worse recurrence-free survival.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Meyer
authors.forename: Vinicius J A
authors.initials: VJ
authors.lastname: Panico
authors.forename: Heloisa M F
authors.initials: HM
authors.lastname: Marconato
authors.forename: David L
authors.initials: DL
authors.lastname: Sherr
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: Edyta C
authors.initials: EC
authors.lastname: Pirog
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000472:pathogenicity; D006679:HIV Seropositivity / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000821:virology; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011379:Prognosis; D015996:Survival Rate
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins