Second primary lung malignancy following head and neck squamous cell carcinoma.

Objectives/hypothesis: Analyze the characteristics of second primary lung malignancies (SPLMs) following an index head and neck squamous cell carcinoma (HNSCC).

Study Design: Retrospective cohort study.

Methods: The Surveillance, Epidemiology and End Results database was queried for all cases of HNSCC between 1973 and 2014 (N = 101,856). This population was compared to a standard population to assess relative risk for lung cancer, calculated as the standardized incidence ratio (SIR). Patients who developed SPLMs were extracted (N = 8,116) and compared to all other cases of lung cancer (N = 1,160,853) to assess histopathological differences. SPLM subpopulations divided by head and neck primary site were compared for lung cancer histology and time interval between cancer diagnoses.

Results: Overall, 8.0% of HNSCC patients developed SPLMs (SIR = 4.22, P < .001), diagnosed an average of 6.7 years later. Patients with HNSCC of the supraglottis and hypopharynx were at the highest risk relative to a standard population, with SIRs of 8.10 and 6.34, respectively. When comparing SPLMs to all other lung cancers, there was no difference in the distribution of lung lobe affected, but SPLMs were significantly more likely to be of squamous cell carcinoma histology (42.0% vs. 21.0%, P < .001). Among head and neck subsites, lung cancers following larynx tumors had a significantly higher proportion of small cell histology, and those following oropharyngeal or hypopharyngeal tumors had significantly higher proportions of squamous cell histology.

Conclusions: Patients who undergo curative treatment of HNSCC are at high risk for developing SPLMs. Subsite-specific differences may help elucidate the degree of risk attributable to smoking, genetic susceptibility, human papillomavirus infection, or metastasis masquerading as an SPLM.

Level Of Evidence: 4 Laryngoscope, 129:903-909, 2019.