Prognostic value of human papillomavirus and squamous cell carcinoma antigen in head and neck squamous cell carcinoma

Abstract

To clarify the synergistic influence of human papillomavirus (HPV) status and squamous cell carcinoma antigen (SCCA) mRNA expression on head and neck squamous cell carcinoma (HNSCC) prognosis, HPV DNA presence and SCCA1 and SCCA2 mRNA expression were determined by PCR and quantitative real-time RT-PCR, respectively, in 121 patients with primary HNSCC who were receiving curative treatment. HPV DNA was detected in 28.1% (34/121) of HNSCC cases, and only high-risk types (HPV-16, HPV-33, HPV-35 and HPV-58) were observed. Positive HPV status showed a significantly better prognosis than negative HPV status (P = 0.022). An elevated SCCA2/SCCA1 mRNA ratio was an independent predictor of disease recurrence (P = 0.004). In addition, HPV-negative patients with a high SCCA2/SCCA1 ratio (>0.27) had a significantly lower recurrence-free survival rate than HPV-negative patients with a low SCCA2/SCCA1 ratio (P < 0.011). Our findings revealed that both HPV status and the SCCA2/SCCA1 mRNA ratio are independently associated with prognosis in HNSCC. Patients with both a HPV-negative status and a high SCCA2/SCCA1 ratio might need intensified treatment and rigorous follow up after treatment because of the high risk of recurrence.

Figure 1

Immunohistochemistry of squamous cell carcinoma antigen (SCCA) 1 and 2 in head and neck squamous cell carcinoma (A–F, oropharyngeal carcinoma) and non‐malignant tonsil (G–I). (A), (D) and (G) show specimens stained with H&E (A, ×100, bar = 100 μm; D, ×400, bar = 30 μm; and G, ×200, bar = 50 μm). (B) and (E), and (C) and (F) exhibit strong cytoplasmic accumulation of SCCA1 and SCCA2, respectively (B and C, ×100, bar = 100 μm; E and F, ×400, bar = 30 μm). (H) and (I) show weak immunoreactivity of SCCA1 and SCCA2, respectively (H and I, ×200, bar = 50 μm).

Figure 2

Relative signal intensity (RSI) of squamous cell carcinoma antigen (SCCA) mRNA expression in non‐malignant tonsillar tissue and head and neck squamous cell carcinoma (HNSCC). (A) SCCA1 and SCCA2 mRNA expression. TS1, SCCA1 of non‐malignant tonsils; HN1, SCCA1 of HNSCC; TS2, SCCA2 of non‐malignant tonsils; HN2, SCCA2 of HNSCC; LA1, SCCA1 of HNSCC with a low SCCA2/SCCA1 ratio; HA1, SCCA1 of HNSCC with a high SCCA2/SCCA1 ratio; LA2, SCCA2 of HNSCC with a low SCCA2/SCCA1 ratio; HA2, SCCA2 of HNSCC with a high SCCA2/SCCA1 ratio. (B) Comparison of SCCA2/SCCA1 mRNA ratios. TS, SCCA2/SCCA1 mRNA ratio in non‐malignant tonsillar tissue; HN, SCCA2/SCCA1 mRNA ratio in HNSCC; R‐HN, SCCA2/SCCA1 mRNA ratio in recurrent HNSCC; nR‐HN, SCCA2/SCCA1 mRNA ratio in non‐recurrent HNSCC.

Figure 3

Kaplan–Meier curves of recurrence‐free survival in head and neck squamous cell carcinoma (HNSCC) patients. (A) Recurrence‐free survival between human papillomavirus (HPV)‐positive and HPV‐negative HNSCC. (B) Recurrence‐free survival between the low and high SCCA2/SCCA1 ratios of HNSCC. (C) Recurrence‐free survival in the four groups defined by HPV presence and the SCCA2/SCCA1 ratio for HNSCC. High SCCA2/SCCA1 ratio, >0.27; low SCCA2/SCCA1 ratio, ≤0.27. SCCA, squamous cell carcinoma antigen.

Figure 4

Kaplan–Meier curves of recurrence‐free survival in patients with oropharyngeal cancer. (A) Recurrence‐free survival between human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal cancer. (B) Recurrence‐free survival in the four groups defined by HPV presence and SCCA2/SCCA1 ratio for oropharyngeal cancer. High SCCA2/SCCA1 ratio, 0.27; low SCCA2/SCCA1 ratio, ≤0.27. Because HPV‐positive patients with a low SCCA2/SCCA1 ratio had an identical recurrence‐free survival to HPV‐positive patients with a high SCCA2/SCCA1 ratio, the two Kaplan–Meier curves overlapped. SCCA, squamous cell carcinoma antigen.