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The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

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The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

Christina S Kong et al. Int J Radiat Oncol Biol Phys.

Abstract

Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status.

Methods and materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16(INK4a) staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO(2) and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining).

Results: Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16(INK4a) staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16(INK4a) staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO(2) or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors.

Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.

Conflict of interest statement

Conflict of interest: none.

Figures

Fig. 1
Fig. 1
(a) Representative agarose gel stained with ethidium bromide for fragment size determination (at expected size of ∼185 base pairs) and polymerase chain reaction (PCR) amplification yield for the L1 region of human papillomavirus (HPV) genome. The gel shows PCR results for samples with strong, weak, and negative signal intensity based on measured amplicon concentration (undectable level as negative, <100 ng/10 μL as weak and ≥100 ng/10 μL strong). (b) Box and whisker plot, showing the quantitative real-time PCR results for HPV L1 signals normalized against β-globulin in 12 randomly selected samples: 6 from the HPV pyrosequencing strong group and 6 from the HPV pyrosequencing weak group.
Fig. 2
Fig. 2
(a) Time to progression by human papillomavirus (HPV) pyrosequencing status for all patients. (b) Overall survival by HPV pyrosequencing status for all patients. (c) Time to progression by HPV pyrosequencing status for the subset of patients with oropharyngeal carcinoma (n = 49). (d) Overall survival by HPV pyrosequencing status for the subset of patients with oropharyngeal carcinoma (n = 49)
Fig. 3
Fig. 3
(a) Time to progression by p16INK4a status for all patients. (b) Overall survival by p16INK4a status for all patients.
Fig. 4
Fig. 4
(a) Time to progression by human papillomavirus (HPV) and p16INK4a status combined for all patients. (b) Overall survival by HPV and p16INK4a status combined for all patients. HPV(S) = strong HPV signal; HPV(NW) = negative or weak HPV signal.

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