The purpose of this study was to determine whether changes in human papillomavirus (HPV) DNA prevalence in oral rinses and/or HPV-specific antibody levels in the sera of patients with oral/oropharyngeal cancer have prognostic significance. One hundred and forty-two patients with oral/oropharyngeal tumors were enrolled. The presence of HPV DNA was assayed in tumor tissue and oral rinses and HPV-specific antibodies were assessed in the sera. Oral rinses were collected before treatment and one year after the treatment. Sera were drawn before treatment, one month, and one year after the end of the treatment. Altogether, 59.2% of tumors were HPV positive. The presence of HPV DNA in the tumors correlated with HPV DNA positivity in oral rinses and with HPV-specific antibodies in the sera. Out of 66 patients with HPV-positive oral rinses at enrolment, 84.8% became negative at one-year follow-up, while most patients remained seropositive for HPV-specific antigens. However, the mean titers of HPV16 E6 and/or E7 antibodies at follow-up were significantly lower. Of 16 patients with recurrences at followup (alive on second sampling), six were positive at enrolment for HPV16 E6 and/or E7 antibodies. In five of these, no decrease in antibody levels was observed. Titers of antibodies specific for HPV16 capsid antigens did not change during the follow-up. Our data suggest that the detection of antibodies specific for the HPV 16 E6 and E7 oncoproteins may serve not only as a marker of HPV etiology, but also as a marker of recurrence and a prognostic indicator in patients with HPV-positive tumors.Squamous cell carcinoma of the head and neck (SCCHN) accounts annually for 7% of all new cancer cases worldwide. 1 SCCHN presents as a single clinical and pathological entity, yet studies conducted over the past 15 years have revealed that it has two distinct etiologies. Most SCCHN cases, particularly those located in the oral cavity, larynx, and hypopharynx, are apparently independent of viral infection, and often associated with tobacco and alcohol use. However, 26% of all SCCHN cases, and over 70% of those found in the tonsillar area and oropharynx, are associated with the presence and expression of mucosal high-risk (oncogenic) human papillomavirus (HR HPV) genomes. [2][3][4] HR HPVs cause cervical cancer and other neoplasms of the anogenital skin and mucosae. 5,6 The most common genital mucosal HR HPV type 16, is found in 95% of HPVpositive SCCHN lesions. 7,8 Although patients with HR HPVassociated SCCNH often present with more advanced disease, we and others have shown that these patients have a remarkably better prognosis and five-year survival rate. 2,9-11 The prognostic advantage of patients with SCCHN etiologically linked to HR HPV could potentially lead to modified treatment regimens. Therefore, noninvasive or less invasive sampling procedures to identify patients with HPV-positive tumors were evaluated in several studies including ours. 12-16It has been demonstrated that the presence of HPV DNA in oral rinses or saliva as well...

The association of high-risk human papillomaviruses (HR HPVs) with tonsillar cancer (TC) has been documented. Because patients with HPV-associated tumors show better survival rates, modification of their treatment regimen is being considered. It is therefore crucial to find markers for the identification of patients whose tumors are linked to viral infection. A cohort of 109 patients with primary TC was screened for HPV DNA presence in the tumor tissues and HPV-specific antibodies in sera. Data regarding risk factors and clinical parameters were collected. Forty-five specimens were analyzed for the expression of viral E6 and E2-region mRNA, and the p16 and p53 protein expression status was assessed by immunohistochemistry. The overall prevalence of HPV DNA in TC tissues was 65.1%. Ninety-three percent of HR HPV DNA-positive samples expressed E6*I mRNA. E2-region mRNA expression was detected in 36% of positive samples, which implies that the virus is integrated in 64% of HPV DNA/RNA-positive tumors. p16 overexpression and the presence of antibodies specific to HPV16 E6/E7 oncoproteins correlated well with HPV DNA and RNA presence. The disease-specific survival rate of patients with HPV DNApositive tumors was significantly higher than that of HPV DNA-negative patients. In addition to providing further evidence of the involvement of HPV infection in the etiopathogenesis of a proportion of TC cases, our study demonstrates that p16 immunostaining and anti-E6/E7 antibodies as surrogate markers of HPV involvement represent specific, sensitive and clinically accessible assays for the identification of TC patients who have a considerably better prognosis.Recent studies have shown that 20-25% of head and neck squamous cell cancers (HNSCCs) appear to be causally linked with high-risk human papillomavirus (HR HPV) infection.