Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16and 18 in patients with head-and-neck squamous-cell carcinoma

Human papillomaviruses (HPVs) have been recognized as an essential pathogen ic factor in anogenital cancer. HPV DNA has also been found in a subgroup o f head-and-neck squamous-cell carcinomas (HNSCCs), and a causative role of the virus in the development of these tumors has been suggested by the conc omitant inactivation of the tumor-suppressor protein pRb, Using 4 second-ge neration ELISAs, we found antibodies against at least 1 of the oncoproteins E6 and E7 of the high-risk HPV types 16 and 18 in 11 of 92 sera (12%) take n from HNSCC patients at or near diagnosis. in 1 of 52 sera (2%) taken from HNSCC patients >6 months after diagnosis and in 10 of 288 sera (3.5%) take n from sex- and age-matched healthy control individuals of the normal popul ation. In 11 of the 12 seropositive HNSCC cases, antibodies were directed a gainst HPV16 proteins. In patients, the HPV16 antibodies were mostly of hig h titer, and in 6 cases, antibodies against both HPV16 oncoproteins were pr esent. Seven of the 8 HPV16 antibody-positive sera from the control group w ere of low titer, and none of the 10 antibody-positive sera reacted with bo th oncoproteins of the same HPV type. The HPV type of the antigens detected by the antibodies in HNSCC patients correlated well with that of the HPV D NA found in the tumor. Of 19 patients known to have HPV16 DNA-positive tumo rs, 7 (37%) also had HPV16 E6 and/or E7 antibodies. Our finding suggests th at the antibodies were formed in an immune response against HPV E6 and E7 p roteins expressed in the HNSCC and thus strongly supports the concept of a biologically active role of HPV in the development of a subgroup of HNSCC. (C) 2000 Wiley-Liss, Inc.