title: Prognostic value of human papillomavirus in anal squamous cell carcinoma.
abstract: OBJECTIVE
  Anal cancer is an uncommon malignancy, but its incidence is increasing worldwide. Chemoradiation is the standard primary treatment for patients with loco-regional limited disease. However, once patients develop metastatic spread, the prognosis is very poor. Human papillomavirus (HPV) is present in around 80 % of anal cancers, but its prognostic and/or predictive value is essentially unknown in this disease.
  
  
  METHODS
  We retrospectively evaluated 50 patients with the diagnosis of anal squamous cell carcinoma treated at our institution with combined chemoradiotherapy for loco-regional limited disease. HPV status was evaluated from paraffin-embedded tumor tissues collected at the time of diagnosis by a polymerase chain reaction analysis.
  
  
  RESULTS
  Among 50 patients, 42 (84 %) were HPV-positive. Thirty-two (64 %) patients were positive to genotype 16, two (4 %) to genotype 18, and three (6 %) to both 16 and 18. Lymph nodal involvement and clinical stage at diagnosis were more advanced for HPV-positive patients. After a median follow-up of 4 years (range 0.4-13.8), 46 (92 %) patients were alive. Overall, eight patients relapsed: One regional, one loco-regional, and six distant recurrences were observed. Four patients died of metastatic disease. Five-year disease-free survival (DFS) in HPV-positive and HPV-negative patients was 92.5 and 50.0 %, respectively (P < 0.01). In multivariate analysis, HPV-positivity was associated with a statistically significant better 5-year DFS (HR HPV+ vs HPV- 0.10; 95 % CI 0.02-0.50). Five-year overall survival in HPV-positive and HPV-negative patients was 93.3 and 66.7 %, respectively (P = 0.12).
  
  
  CONCLUSIONS
  In our study, HPV-positive anal cancers had a statistically significant improved DFS compared to HPV-negative group.
authors.affiliation: Unit of Gastrointestinal and Neuroendocrine Tumors, Division of Medical Oncology, European Institute of Oncology (IEO), Via Ripamonti 435, 20141, Milan, Italy, paolasimona.ravenda@ieo.it.
authors.forename: Paola Simona
authors.initials: PS
authors.lastname: Ravenda
authors.forename: Elena
authors.initials: E
authors.lastname: Magni
authors.forename: Edoardo
authors.initials: E
authors.lastname: Botteri
authors.forename: Michela
authors.initials: M
authors.lastname: Manzotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Barberis
authors.forename: Davide
authors.initials: D
authors.lastname: Vacirca
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Trovato
authors.forename: Veronica
authors.initials: V
authors.lastname: Dell'Acqua
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Leonardi
authors.forename: Mario
authors.initials: M
authors.lastname: Sideri
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Zampino
mesh_terms: D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics* / Q000502:physiology; D001005:Anus Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000628:therapy* / Q000821:virology; D059248:Chemoradiotherapy; D004279:DNA, Viral / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000528:radiation effects; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology; D052161:Human papillomavirus 18 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D030361:Papillomavirus Infections / Q000473:pathology / Q000628:therapy* / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D004279:DNA, Viral