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Use of Serum HPV16 DNA as a Marker for Oropharyngeal Cancer Recurrence

$77,000R03FY2008CANIH

University Of Tx Md Anderson Can Ctr, Houston TX

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Abstract

RESEARCH AND RELATED Other Project Information 6. Project Summary/Abstract Infection with HPV16 is strongly associated with squamous cell carcinoma of the oropharynx (SCCOP) and is detected in approximately 50% of these tumors. In a small study of patients with squamous cell carcinomas of the head and neck as well as studies of women with cervical cancer, detection of HPV16 DNA in peripheral blood appears to be a predictor of tumor recurrence. Larger studies from several institutions have utilized a similar concept with significant success in patients with nasopharyngeal carcinoma. In these studies, the presence of EBV DNA in the sera of patients was an indicator of recurrence or metastasis. Furthermore, viral DNA load can be an earlier indicator of recurrence than clinical exam or imaging. It is our hypothesis that the presence of HPV16 in peripheral blood of SCCOP patients will be an early indicator of recurrent disease and in particular distant metastatic disease. To test this hypothesis, we will recruit 188 patients with SCCOP and determine via real-time PCR whether the patients have detectable HPV16 E6 or E7 DNA in their sera both before and after treatment. Follow-up (including timing, frequency, imaging, and blood work) will be determined by the treating clinicians. Blood will be obtained approximately 6 weeks after completion of radiotherapy and approximately every 6 months for 3 years (greater than 90% of recurrences will occur within 3 years of treatment). The final goal of this project is to expand on an existing pilot study of HPV16 and SCCOP funded by our institutional research funds to investigate whether the presence of HPV16 in peripheral blood of SCCOP patients will be an early indicator of clinical outcome of the disease. By using HPV16 DNA in sera as a disease marker in patients with SCCOP we may determine which patients are at high risk for disease recurrence/metastasis they may have significant implications for the development of tailored treatment or prevention of recurrent or metastatic disease, and potentially enrolled in experimental protocols for more aggressive systemic management. Secondly, in follow-up such a marker may have utility in earlier detection of recurrent disease, which at present has an extremely poor prognosis. RESEARCH AND RELATED Other Project Information 7. Project Narrative Nationally, the incidence of SCCOP in young adults (<45 years of age, generally lacking significant tobacco exposures) is increasing, and this rise in incidence may be related to changes in HPV16 prevalence and in the sexual practices of American teenagers and young adults. If the association between serum HPV16 DNA and oropharyngeal cancer recurrence is confirmed, it may be possible to intensify treatment in patients who have measurable levels before treatment, add adjuvant therapy for those with measurable levels immediately after treatment, and intensify workup for treatable recurrent disease in those who are found to have elevated levels in follow-up. By determining which patients are at the highest risk for recurrence they may be evaluated more aggressively at presentation, monitored more closely after treatment, and potentially enrolled in experimental protocols for more aggressive systemic management for better opportunity to successfully treat such disease and better quality of life.

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