Risk of second primary cancer in patients with head and neck squamous cell carcinoma: a systemic review and meta-analysis

Abstract

Objectives: Second primary cancer is a common event in patients with head and neck squamous cell carcinoma. However, the incidence and relevant factors vary by studies. We conducted a systematic review and meta-analysis of observational studies to estimate the incidence and relevant risk factors.

Materials and methods: PubMed and Web of Science were searched for studies published between January 2000 and December 2020 that reported the incidence of SPC in HNSCC patients. Per 1000-person-year incidence and odds ratios were used to estimate the incidence and potential risk factors. Due to the high heterogeneity, random-effects models were used to estimate the incidence and 95% confidence interval.

Results: Seven thousand seven hundred thirteen articles were identified from the databases, in which 60 studies were included in this meta-analysis. The pooled incidence of the total, synchronous, and metachronous SPC in patients with HNSCC were 29.116 per 1000-person-year, 6.960 per 1000-person-year, and 26.025 per 1000-person-year, respectively. The head and neck region was the most common area where SPC occurred, followed by the lung (7.472 per 1000-person-year) and upper digestive tract (2.696 per 1000-person-year). Smoking, alcohol consumption, betel quid chewing, primary cancer of T_1-2, and N₀ were risk factors, while HPV infection (OR 0.47, 95% CI 0.30-0.72) was the protective factor.

Conclusions: SPC is frequently observed in HNSCC patients and had great impact on the prognosis. The findings could promote a more individualized follow-up strategy for SPC in HNSCC patients.

Clinical relevance: This systemic review and meta-analysis provide sufficient evidence for the establishment of the follow-up strategy for head and neck squamous cancer patients.

Keywords: Head and neck squamous cell carcinoma; Meta-analysis; Person-year incidence; Risk factors; Second primary cancer.