Introduction/Background Today, there are two accepted pathways for tumorigenesis of vulvar squamous cell carcinoma (VSCC): an HPV-dependent with p16 overexpression as a surrogate for HPV-associated transformation and an HPV-independent route linked to lichen sclerosus, characterized by p53 mutation. A possible correlation of HPV dependency with a favourable prognosis has been proposed.
Methodology The AGO CaRE-1 study is a retrospective survey of pts with primary VSCC FIGO stage ≥1B (UICC-TNM version 6) treated at 29 gynecologic cancer centers in Germany 1998–2008 (n=1,618). For this CaRE-translational sub-study available FFPE tissue was collected centrally (n=648). A tissue micro array (TMA) was constructed; p16 and p53 expression was determined by immunohistochemistry (IHC). HPV status and subtype were analyzed by PCR.
Results p16 IHC was interpretable in 550 TMA spots and considered positive in 166/550 (30.2%). HPV DNA was detected in 78.4% of the p16+ tumors, with HPV 16 being the most common subtype (88.3%). p53 IHC was interpretable in 597 spots, 187/597 (31.3%) were considered positive. Pts with p53+ tumors were older at first diagnosis (71 vs. 66 yrs; p=0.001 for p53- tumors) and showed lymph-node involvement more often (43.3% vs. 31.1%; p=0.007). There was a relevant number of tumors with neither p16 nor p53 overexpression (221/535); while co-expression of p53 and p16 was rare (12/535). For survival analyses, three groups were defined: p53+ (n=163), p16+/p53- (n=151) and p16-/p53- (n=221). 2-y-disease-free (DFS) and overall survival (OS) rates were significantly different between the groups: DFS: p53+ 47.0%; p16-/p53- 53% and p16+/p53- 65.5% (p<0.001); OS: 70.4%, 72.6% and 82.7% (p=0.003), respectively. Adjustment for age and nodal status showed consistent p16 and p53 effects regarding DFS.
Conclusion p16 overexpression is associated with an improved prognosis in VSCC while p53 positivity is linked to an adverse outcome. Our data provide evidence of a clinically.
Disclosure The AGO CaRE translational study was supported by medac oncology without restrictions in the study protocol.
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