Are there immunohistological differences between cervical CUP syndrome and oropharyngeal carcinoma?

Introduction The cause for cervical cancer of unknown primary (CUP) syndrome is as of yet unclear. In recent studies a subcategory of patients with CUP syndrome has been shown to be associated with type 16 HPV, which suggests a possible oropharyngeal origin. To determine if the CUP syndrome is immunologically associated with oropharyngeal carcinomas we analyzed and compared local tumor infiltration with lymphocytes and PD-L1-Status.

Methods We immunohistologically analyzed patients with a cervical CUP syndrome (n = 56) and oropharynx carcinoma (primary tumor n = 60, lymphnode metastases n = 27) and determined the tumor infiltration with T-lymphocytes (CD3 and CD8) as well as the PD-L1 status and correlated them with pathohistological findings. The HPV status (p16 IHC and HPV16 ISH) was determined for both groups and in patients with CUP syndrome additionally the EBV status (EBV ISH).

Conclusions An association with HPV (p16 and HPV16) was found in 20 % of CUP lymphnode metastases and in 32 % of patients with oropharyngeal carcinoma. A positive EBV status was found in two patients with CUP syndrome. The PD-L1 status (TC) was significantly higher in the CUP group as compared to the oropharyngeal cancer group. The prognosis was not found to be associated with a higher proportion of CD3+ and CD8+ tumor-infiltrating lymphocytes in CUP syndrome patients.

Conclusions A higher PD-L1 status was found in patients with cervical CUP syndrome as compared to oropharyngeal cancer patients. This suggests that patients with a CUP syndrome could profit from a checkpoint-inhibitor therapy.

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Publication History

Article published online:
10 June 2020