Differential molecular characterization of human papillomavirus-associated oropharyngeal squamous cell carcinoma and its prognostic value

Abstract

Human papillomavirus (HPV) infection is a causative factor in the occurrence and progression of oropharyngeal squamous cell carcinoma (OPSCC). In recent years, clinical studies have found that HPV-positive OPSCC patients may present a better prognosis than HPV-negative patients, yet the underlying causes are unclear. This study aimed to investigate the relevance of HPV infection and the prognosis of OPSCC. On this basis, we aimed to establish a prediction model to accurately predict the prognosis and guide clinical practice. We analysed the records of 233 patients with OPSCC. Cox regression was applied to identify factors associated with survival. Moreover, variables with significant discrepancies were integrated into a nomogram model to predict prognosis. The results showed that HPV was an independent prognostic factor for OS and PFS. Immunoglobulin Heavy Constant Mu (IGHM) mRNA was significantly upregulated in patients with HPV-positive OPSCC. Crucially, IGHM expression was associated with better prognosis. The receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis both confirmed that the prognostic model exhibits good performance. In summary, HPV infection were independent prognostic factors for OPSCC. IGHM may be the key contributors to the prognostic differences in HPV-associated OPSCC. This nomogram model was able to accurately predict the prognosis of patients.

Keywords: human papillomavirus; oropharyngeal squamous cell carcinoma; overall survival; prognostic factors; progression‐free survival.

FIGURE 1

Kaplan–Meier curves showing the progression‐free survival of oropharyngeal squamous cell carcinoma by univariate analysis, including significantly different results (p < 0.005). (A) Tobacco. (B) Alcohol. (C) Lymphovascular invasion. (D) Clinical stage. (E) T stage. (F) T stage (Regrouped). (G) N stage. (H) p16‐IHC.

FIGURE 2

Kaplan–Meier curves showing the overall survival (OS) of oropharyngeal squamous cell carcinoma by univariate analysis, including significantly different results (p < 0.005). (A) Tobacco. (B) Alcohol. (C) Lymphovascular invasion. (D) Clinical stage. (E) T stage. (F) T stage (Regrouped). (G) N stage. (H) p16‐IHC.

FIGURE 3

(A) The level of the differential gene was summarized from TCGA database. (B) The mRNA level of the differential gene was detected by quantitative real‐time polymerase chain reaction. *p < 0.05 versus HPV negative.

FIGURE 4

Nomogram was used to predict overall survival (OS) of patients with head and neck squamous cell carcinoma from TCGA database. To use this nomogram, the patient's specific point for each variable is located on each variable axis. A vertical line was drawn upward to determine the points for each variable; th4.e sum of these points was located on the total points line, and a vertical line is drawn downward to the survival axis to determine the probability of at OS 1, 2 and 3 years. (A) Nomoplot of OS. (B) Nomoplot of progression free survival.

FIGURE 5

Calibration curves of the nomograms. Calibration curves of 1‐, 2‐ and 3‐year overall survival (A–C) and progression free survival (D–F) for head and neck squamous cell carcinoma patients. The dotted line represents the ideal reference line, where the predicted probability would match the observed survival rate. The red dots are calculated by bootstrapping (resample: 50) and represent the nomogram performance. The closer the solid red line is to the dotted line, the more accurate the model is in predicting OS.

FIGURE 6

Receiver operating characteristic curves of the ability of nomogram to predict 1‐, 2‐ and 3‐year overall survival (A–C), progression free survival (D–F).

FIGURE 7

Decision curve analysis of the nomogram for survival prediction of head and neck squamous cell carcinoma patients. (A) Survival benefit for OS; (B) Survival benefit for PFS.