Abstract
Wild California sea lions (Zalophus californianus) ranging along the west coast of the United States have the highest prevalence of cancer amongst all marine mammal species. Urogenital carcinoma has been diagnosed in approximately 20% of adult sea lions necropsied at California rehabilitation centers and animals in managed care facilities. Otarine Herpesvirus 1 (OtHV1) is a sexually transmitted herpesvirus that plays a causal role in development of urogenital carcinoma. The objective of this study was to determine if OtHV1 in blood can be used as a biomarker to predict whether a sea lion has metastatic urogenital carcinoma. Blood and genital tissue were collected from sea lions and tested for OtHV1 using quantitative polymerase chain reaction. All cases were classified as metastatic urogenital carcinoma (metastatic; n =7), non-invasive (carcinoma in situ; n =9), or non-cancer (control; n =18) based on histology evaluation. Detection of OtHV1 in the blood of all cases were compared to see if circulating herpesvirus was predictive of patients having metastatic urogenital carcinoma.
OtHV1 was identified in the genital tract of 100% (7/7) of metastatic cases, 100% (9/9) of carcinoma in situ cases, and 56% (10/18) of the control cases. OtHV1 was detected in the blood of 86% (6/7) of metastatic cases, 22% (2/9) of carcinoma in situ cases and 11% (2/18) of control cases. There was a significant difference in the detection of OtHV1 in blood samples from metastatic cases compared to carcinoma in situ (Fisher’s exact test p=0.041) and non-cancer cases (Fisher’s exact test p=0.001). Of the two control and two carcinoma in situ cases that tested positive for OtHV1 in their blood, three had chronic parasitism suggestive of generalized immune suppression or severe underlying disease, which may explain why herpesvirus was identified in the blood of these patients. These results support that OtHV1 may be a potential blood biomarker for metastatic disease in sea lions with urogenital carcinoma but may also be suggestive of immune suppression or other underlying disease.