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What is the Risk of Anal Carcinoma in Patients With Anal Intraepithelial Neoplasia III?
*Grace C. Lee1, Hiroko Kunitake1, *Holly Milch1, *Lieba R. Savitt1, *Caitlin Stafford1, Liliana G. Bordeianou1, *Todd D. Francone2, Rocco Ricciardi1
1Massachusetts General Hospital, Boston, MA; 2Newton Wellesley Hospital, Newton, MA

Objective: The primary objective was to quantify the risk of anal squamous cell carcinoma (SCC) in patients with anal intraepithelial neoplasia (AIN). The secondary objective was to identify predictors for malignant transformation.
Design: Retrospective analysis of a population-based patient cohort. Median follow up time was 4.3+/-3.3 years.
Setting: SEER registry (1973-2014).
Patients: All patients diagnosed with AIN III were included in the cohort.
Intervention: n/a
Main Outcome Measures: Whether or when patients with AIN III were diagnosed with anal SCC.
Results: A total of 2,129 patients with AIN III were identified, of whom 173 (8.1+/-1.1%) went on to develop anal SCC. Median time from AIN diagnosis to anal SCC diagnosis was 2.7+/-2.6 years. Fifty-three patients (30.8%) who developed anal SCC were staged T2 or higher. For treatment of initial AIN, 602 patients (28.4%) had no procedure, 298 (14.0%) underwent ablative surgery, and 1,182 (55.7%) underwent excision. Multivariable analysis revealed that ablative therapies for initial AIN were associated with a marked reduction in risk of anal SCC, compared to no procedure (OR 0.3, 95% C.I. 0.1-0.6; p=0.003) (Table 1).
Conclusions: The incidence of anal SCC after AIN III diagnosis is markedly higher than previously reported, as 8.1% of patients in our population-based cohort developed anal cancer. Nearly one-third of anal SCCs were diagnosed at a stage of T2 or higher despite a prior diagnosis of AIN, suggesting that AIN lesions require more vigilant surveillance. Ablative procedures were associated with significantly decreased risk of anal SCC, indicating the effectiveness of this modality.

VariableOdds RatioP-value95% Confidence Interval
Age at diagnosis of AIN
<=40 years oldReference
41-50 years old1.690.0461.012.83
51-60 years old1.110.7200.641.92
>60 years old1.220.5050.682.19
Other (Asian, American Indian)1.390.4690.573.36
Marital status at diagnosis of AIN
Single (never married)Reference
Married or unmarried/domestic partner1.060.7830.691.63
Divorced, separated, or widowed0.490.0410.240.97
Surgery type for AIN
Ablative surgery0.270.0030.110.64
Excisional surgery1.750.0051.192.58
Abdominoperineal resection1.200.8620.159.63
Unspecified surgery, or unknown2.420.1790.678.80

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