Meyer Joshua E, Panico Vinicius J A, Marconato Heloisa M F, Sherr David L, Christos Paul, Pirog Edyta C
Fox Chase Cancer Center, Philadelphia, PA, USA.
J Gastrointest Cancer. 2013 Dec;44(4):450-5. doi: 10.1007/s12029-013-9543-1.
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.
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.
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).
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.
人乳头瘤病毒（HPV）是包括肛管癌（ACA）在内的多种黏膜部位鳞状细胞癌的致病因素。已知HIV阳性患者患ACA的风险很高。本研究的目的是探讨ACA的临床结局与HPV/p16阳性、组织学肿瘤分化及HIV状态之间的关系。据报道，人乳头瘤病毒阳性、p16过表达且具有非角化/基底样组织学特征的口咽癌患者在接受放化疗（CRT）后预后较好。然而，ACA中的此类关系尚不清楚。
确定了1997年至2009年间接受CRT治疗的42例肛管鳞状细胞癌患者。肿瘤被分为非角化（包括基底样）或角化类别。采用SPF10-PCR进行HPV检测，所有病例均进行p16免疫染色。
男性23例，女性19例；43%的男性和11%的女性HIV阳性（p = 0.04）。55%的患者为局部疾病（I期和II期），41%为III期和IV期，4%分期不明。所有肿瘤高危致癌型HPV均为阳性，p16免疫染色均为阳性。64%的肿瘤为非角化/基底样，36%为角化型。角化型肿瘤在HIV阳性患者中更常见（67%），而非角化/基底样肿瘤在HIV阴性患者中更常见（77%）（p = 0.008）。31%的患者出现疾病复发，包括50%的HIV阳性患者和23%的HIV阴性患者（p = 0.09）。非角化和角化肿瘤亚型之间的复发率无差异（p = 0.80）。该队列的24个月无复发生存率为66%（95%CI = 46%，81%），HIV阳性患者的无复发生存率低于HIV阴性患者（HR = 2.85，95%CI = 0.95，8.53；p = 0.06）。
局部和远处失败率与ACA的HPV/p16阳性或组织学分化无关；然而，HIV阳性似乎与较高的复发率和较差的无复发生存率相关。
