Serum levels of soluble tumor-necrosis-factor receptors in patients with benign and malignant HPV-associated anogenital lesions

Abstract

The levels of type‐I and type‐II soluble TNF‐α receptors (sTNF‐Rs) were evaluated in sera from patients with various human‐papillomavirus‐(HPV)‐associated benign and malignant anogenital lesions using specific enzyme‐linked immunobiological assays. In patients with benign HPV6/11‐associated condylomata acuminata, the levels of sTNF‐RI were significantly increased, while sTNF‐RII were in normal range. Both types of sTNF‐Rs were in normal range in patients with benign HPV16‐associated grade‐I/II and grade‐III cervical intra‐epithelial neoplasia. However, their levels were significantly increased in patients with HPV16/18‐associated squamous cervical cancer and anogenital Bowen's carcinoma. Sera from patients with condylomata acuminata and anogenital carcinomas displayed significantly increased TNF‐α‐inhibitory activity, as revealed by L929 cell‐cytotoxicity assay. Increased serum TNF‐α‐inhibitory activity correlated with higher levels of sTNF‐Rs. Furthermore, this inhibitory activity could be specifically abrogated by htr9 and utr1 monoclonal antibodies recognizing TNF‐RI and TNF‐RII respectively. Our results strongly suggest that serum sTNF‐Rs may protect tumor cells from cytotoxic/cytostatic effects of locally released TNF‐α, and that elevated levels of circulating sTNF‐Rs may facilitate the growth of HPV‐associated anogenital lesions. Int. J. Cancer 73:16–19, 1997.