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The prognostic significance of tumor human papillomavirus status for patients with anal squamous cell carcinoma treated with combined chemoradiotherapy
Author(s) -
Yhim HoYoung,
Lee NaRi,
Song EunKee,
Kwak JaeYong,
Lee Soo Teik,
Kim Jong Hun,
Kim JungSoo,
Park Ho Sung,
Chung IkJoo,
Shim HyunJeong,
Hwang JunEul,
Kim Hyeong Rok,
Nam TaekKeun,
Park MooRim,
Shim Hyeok,
Park Hyo Sook,
Kim Hee Sun,
Yim ChangYeol
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25825
Subject(s) - medicine , chemoradiotherapy , stage (stratigraphy) , oncology , immunohistochemistry , gastroenterology , anal cancer , human papillomavirus , clinical significance , tumor progression , cancer , biology , paleontology
The prognostic relevance of tumor human papillomavirus (HPV) status in anal squamous cell carcinoma (SCC) had not been previously investigated, although its relevance to cervical, head and neck SCC is known. We retrospectively evaluated outcomes in 47 patients with anal SCC treated with combined chemoradiotherapy (CCRT) and determined tumor HPV status by HPV DNA chip method and p16 expression by immunohistochemistry (IHC) from paraffin‐embedded tumor tissues. The median age was 65 years (range, 44–90 years). Sixteen (34%) patients were diagnosed with T stage 3 to 4, and 18 (38%) patients had regional nodal disease (N‐positive). Thirty‐five (75%) patients were HPV positive, and 31 (66%) patients were genotype 16 (HPV16‐positive). Thirty‐nine (83.0%) patients were positive for p16. After median follow‐up of 51.7 months (range, 5.1–136.0 months), HPV16‐positive group had significantly better 4‐year progression‐free survival (PFS, 63.1% vs . 15.6%, p < 0.001) and overall survival (84.6% vs . 39.8%, p = 0.008) than HPV genotype 16 negative (HPV16‐negative) group. Patients with p16‐positive tumor also had a better 4‐year PFS (52.5% vs . 25.0%, p = 0.014) than those with p16‐negative tumor. In multivariate analysis for PFS, N‐positive and HPV16‐negative were independent prognostic factors for shorter PFS. Comparing patterns of failure, time to loco‐regional failure was statistically superior in HPV16‐positive over HPV16‐negative groups ( p = 0.006), but time to systemic failure was not different ( p = 0.098). Tumor HPV genotype 16 status is a prognostic and predictive factor in anal SCC treated with CCRT, and p16 expression determined by IHC might be advocated as a surrogate biomarker of HPV integration in anal SCC. Further studies are warranted.