The prognostic significance of tumor human papillomavirus status for patients with anal squamous cell carcinoma treated with combined chemoradiotherapy.
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.
Division of Hematology/Oncology, Chonbuk National University Medical School, Jeonju, Korea.
Ho-Young
HY
Yhim
Na-Ri
NR
Lee
Eun-Kee
EK
Song
Jae-Yong
JY
Kwak
Soo Teik
ST
Lee
Jong Hun
JH
Kim
Jung-Soo
JS
Kim
Ho Sung
HS
Park
Ik-Joo
IJ
Chung
Hyun-Jeong
HJ
Shim
Jun-Eul
JE
Hwang
Hyeong Rok
HR
Kim
Taek-Keun
TK
Nam
Moo-Rim
MR
Park
Hyeok
H
Shim
Hyo Sook
HS
Park
Hee Sun
HS
Kim
Chang-Yeol
CY
Yim
D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
D004279:DNA, Viral