Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma.

OBJECTIVES/HYPOTHESIS: The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients. STUDY DESIGN: Retrospective study. METHODS: Paraffin-embedded samples from OSCC patients (n = 162) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus polymerase chain reaction (PCR) and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, and 68. Immunohistochemical staining for p16, p53, and EGFR was also performed. RESULTS: The type-specific E6/E7 PCR demonstrated that 65 of the 147 OSCC patients (44%) presented with high-risk (hr) HPV types and that 38 of the 147 OSCC patients (26%) presented with low-risk (lr) HPV types. Comparable p53 and EGFR expression levels were observed in the hr HPV+ group (41.5% p53+, 92% EGFR+) and the lr HPV+ group (57% p53+, 92% EGFR+). Conversely, a slight increase in the proportion of p16+ tumors was observed in the hr HPV+ group (65%) compared with the lr HPV+ group (44%). In regard to patient outcome, the presence of HPV was correlated with a worse prognosis (P = .007). CONCLUSIONS: A high prevalence of hr and lr HPV infections was detected in the OSCC patients included in the study. Moreover, hr HPV positivity was correlated with a decreased 5-year disease-free survival rate compared with HPV- and lr HPV+.

High incidence of high-risk HPV in benign and malignant lesions of the larynx.

The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5+/GP6+ consensus PCR and E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10-6). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV+ tumor group (100% p16+, 56% p53+ and 97% EGFR+) and in the HPV- or low-risk (lr) HPV+ tumor group (92% p16+, 66% p53+ and 100% EGFR+). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV+ subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV- subgroup.

High prevalence of high-risk human papillomavirus in palatine tonsils from healthy children and adults.

OBJECTIVE: The aim of this study was to determine the prevalence of human papillomavirus (HPV) in 80 tumor-free tonsils from healthy children and adults using a sensitive E6/E7 type-specific polymerase chain reaction (PCR). STUDY DESIGN: Cross-sectional study. SETTING: Ear, nose, and throat department, university hospital. SUBJECTS AND METHODS: Paraffin-embedded tissues from tumor-free tonsils (TFTs) were evaluated for HPV DNA using GP5+/6+ consensus PCR and subsequent genotyping using E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68. The immunohistochemical expression of p16 and p53 was also assessed. RESULTS: In 80 TFTs, the authors identified 10 (12.5%) that tested positive for the following high-risk HPV types: HPV 16 (8 cases), 18 (1 case), and 31 (1 case). Twelve patients (15%) tested positive for HPV infection using the GP5+/GP6+ consensus primers but were negative using quantitative PCR. These patients were considered infected with low-risk HPV types. Fifty-eight TFTs (72.5%) tested negative for both GP5+/GP6+ and type-specific HPV PCR analysis (HPV negative). Among patients infected with HPV, the authors observed a slight increase in frequency with age. CONCLUSION: In TFTs, oncogenic and nononcogenic HPVs were present at a relatively high frequency in children and adults. The presence of high-risk HPV DNA in young children supports the horizontal transmission hypothesis and argues in favor of HPV vaccination at birth.

Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma.

PURPOSE: We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC). METHODS: Paraffin-embedded tumours from HSCC patients (n = 75) were evaluated for p16, p21 and p53 expression by immunohistochemistry. HPV DNA was detected by GP5+/6+ consensus PCR and subsequent genotyping by E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. RESULTS: Among the 61 specimens that tested positive for the ß-globin, HPV typing identified 50 patients with high-risk (hr) HPV types. HPV 16E7 DNA was detected in 74% (37 cases) of these specimens. Twelve patients were found to be infected with multiple HPV types. However, the presence of hrHPV DNA was not found to correlate with the proportion of disease-free patients. The 5-year disease-free survival rate was 73% in p53- tumours versus 48% in p53+ tumours (P = 0.008). CONCLUSION: In our series of patients with stage IV HSCC, the hrHPV+ subgroup had a similar prognosis (in terms of recurrence risk) as the HPV- subgroup. p53 overexpression was associated with a worse prognosis.