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Dong Wook Lee, MD; Mary E. Anderson, BS; Shu Wu, MS; John H. Lee, MD

Arch Otolaryngol Head Neck Surg. 2008;134(12):1316-1323.

Objectives  To test whether an immunization strategy that targets the E6 and E7 oncoproteins (E6/E7) may be an effective means to prevent the development of human papillomavirus (HPV)–positive head and neck squamous cell cancers using an in vivo mouse model and to determine whether such a response would prevent the establishment of viral transformed cells in vivo.

Design  Adenoviral recombinant vaccine expressing HPV-16 E6/E7 (adenovirus 5 E6/E7, or Ad5 E6/E7) was generated. Specificity and timing of the E6/E7-specific cellular immune response was determined in vivo. Adenovirus 5 E6/E7 efficacy and route of administration required for clearance of HPV–positive tumor cells were monitored.

Results  We generated Ad5 E6/E7 oncoproteins. Splenocytes from mice immunized with Ad5 E6/E7 produced interferon (IFN)- to cells expressing E6/E7 but not to cells lacking these oncoproteins. A time course of IFN- response showed that E6/E7-specific IFN- production is significantly increased in the first 2 weeks after administration of the vaccine and is substantially maintained for up to 70 days. Inoculated mice cleared E6/E7-expressing tumor 70 days after implantation. At all dosages of vaccine, mice inoculated with Ad5 E6/E7 completely cleared E6/E7-expressing tumor cells implanted 2 weeks after either intratracheal or submucosal inoculation, with significant E6/E7-specific IFN- production.

Conclusions  Immunization with HPV–16 E6/E7 oncoproteins can be an effective method of protecting a host from E6/E7-expressing head and neck squamous cell cancers via generation of a potent immune response. Such a response may be beneficial when combined with traditional treatment such as surgery, chemotherapy, or radiotherapy, thus improving the prognosis and quality of life of patients with HPV-16–associated head and neck squamous cell cancers.

Author Affiliations: Department of Otolaryngology–Head and Neck Surgery, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa (Drs D. W. Lee and J. H. Lee and Mss Anderson and Wu); and Department of Otolaryngology–Head and Neck Surgery and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea (Dr D. W. Lee). Dr J. H. Lee is now with the Department of Otolaryngology–Head and Neck Surgery, Sanford Research/USD, Sanford School of Medicine, University of South Dakota, Sioux Falls.

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