Diagnosis, treatment and oncological outcome of cervical CUP-syndrome depending on p16 status

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The incidence of cervical squamous cell carcinoma (SCC)-CUP is increasing, with a significant proportion being HPV-associated. In this 10-year retrospective study, we analyzed clinical and therapeutic parameters of patients with cervical SCC-CUP. Primary tumor detection rates in patients with initial SCC-CUP (SCC-CUPinit) were assessed and mean overall survival and disease-free survival of patients without primary tumor detection after an extended diagnostic workup, i.e. definitive SCC-CUP (SCC-CUPdef), were analyzed taking p16-status into account to derive therapeutic recommendations.85% (n=131/155) of patients with CUPinit, presented with SCC followed by adenocarcinoma metastases in 7% (n=10/155). In 41% (n=54/131) of patients with SCC-CUPinit, a primary tumor was identified after an extended diagnostic workup; the primary tumor detection rate was significantly higher in p16-positive compared to p16-negative cases (63% vs. 23%, p<0,001). PET imaging specificity was 73% for both sensitivity and specificity. SCC-CUPdef were primarily treated surgically with adjuvant radio(chemo)therapy. SCC-CUPdef patients with positive vs. negative p16-status had significantly longer overall survival (53 vs. 41 Monate, p=0,037), as well as patients with cN1- vs. cN3-status and M0- vs. M1-status.p16-status influences diagnosis and therapy response in patients with SCC-CUP: in p16-positive SCC-CUPinit, primary tumor detection rates were significantly higher than in p16-negative SCC-CUPinit. In patients with SCC-CUPdef, p16-positivity was associated with improved overall survival, albeit to an extent which does not justify therapy de-escalation.