The Prognostic Significance of Human Papillomavirus (HPV) in Invasive and In Situ Squamous Cell Carcinoma (SCC) of the Anus
L Stoll, M Johnson, E Montgomery. Johns Hopkins Hospital, Baltimore
Background: HPV, particularly HPV 16, plays a strong role in SCC of the anus. Current prognostic factors for treatment and survival do not include HPV status. However, high risk HPV has been associated with improved outcomes and response to treatment within the context of oropharyngeal SCC. We studied the impact of high risk HPV status on disease progression and prognosis in anal SCC.
Design: A computer search of a large teaching hospital identified 59 cases over 23 years (1984-2007) including invasive (n=31) and in situ lesions (n=28). Patients lacking available pathologic follow-up were excluded (n=14) yielding a total of 22 invasive and 23 in situ cases (n = 45). Chart review was conducted to determine age, sex, HIV status, and stage at initial presentation. Tissue sections from 45 cases were analyzed by p16 immunohistochemistry. Cases showing p16 expression were subjected to HPV 16-specific fluorescence in situ hybridization (FISH). HPV status was then correlated with the aforementioned patient variables.
Results: The average patient age was 47 years (25 86 years) with a slight male predominance (n=26). HIV status was known in 19 patients, 12 HIV positive. Among invasive lesions 81% (n=18) showed p16 expression, with HPV 16 detected in 41% of cases. These all presented de novo as invasive SCC. Seventy percent (n=16) of in situ lesions showed p16 upregulation with detection of HPV 16 in 22% of cases. The rate of HPV 16 prevalence did not differ significantly between in situ versus invasive SCC (p=0.14). Four in situ lesions progressed to invasive SCC. Expression of p16 was detected in 1/4 progressive cases, while 3 showed no p16 upregulation. HPV 16 was absent in all 4 cases. Among those maintaining an in situ lesion 79% showed p16 expression, with only 26% having HPV16 detected. Finally, within invasive SCC, p16 upregulation and the presence of HPV 16 did not statistically correlate with disease prognosis as defined by stage. Eighty-six percent of persons with stage 2 disease, and 75% with stage > 2 disease were shown to have p16 upregulation. HPV-16 was detected in 43% of persons with stage 2 disease, and 38% with stage > 2 disease. No significant correlation was seen with HIV status.
Conclusions: HPV 16 is the most commonly associated HPV subtype with anal SCC. While HPV is a known etiologic factor in carcinogenesis, it is not a prognostic factor for disease as defined by stage in this study, nor does it influence in situ disease progression. Location, tumor size, and patient age remain the most important prognostic factors.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 84, Wednesday Morning