Significant risk of second primary cancer among laryngeal squamous cell carcinoma patients even after 20 years

Abstract

Background

Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe.

Methods

Patients diagnosed with primary LSCC from 1953–2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included.

Results

A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52–1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19–11). The corresponding SIR for women was 1.47 (95% CI: 1.15–1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36–9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49–2.01 and EAR 16.8 per 1000 PY, 11.88–23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36–3.95 and EAR 0.80 per 1000 PY, 0.55–1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13–6.78).

Conclusion

Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.

NOVELTY & IMPACT

Although prior research on the risk of second primary cancer (SPC) among laryngeal squamous cell carcinoma (LSCC) patients has been conducted in other regions, the European perspective remains notably underrepresented. Moreover, studies on the subject focusing especially on LSCC are, even globally, only a few. The present study, with over 6000 LSCC patients followed-up over six decades, consists of the largest reported cohort of LSCC patients in Europe, and with the longest follow-up. Patients with LSCC as a primary cancer have a 60% excess risk for an SPC, which remains significantly elevated even 20 years after the diagnosis of the first primary cancer, especially for those with a tobacco/alcohol-related cancer. Healthcare professionals should be aware of the SPC risk among LSCC survivors who should be counseled about this phenomenon.

Keywords:

• Head and neck cancer
• risk
• laryngeal cancer
• second primary cancer

Author’s contributions

Rayan Nikkilä, Elli Hirvonen, Aaro Haapaniemi, Laura Tapiovaara, Janne Pitkäniemi^, Nea Malila, Antti Mäkitie conceived and designed the study. Elli Hirvonen conceived the data. Rayan Nikkilä and Elli Hirvonen analyzed the data. Rayan Nikkilä devised the first draft of the manuscript. All authors contributed to the revision of the manuscript and had final approval of the submitted and published versions.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data sharing not available due to privacy/ethical restrictions

Additional information

Funding

This work was supported by the Sigrid Jusélius Foundation, Finska Läkaresällskapet, the State Research Funding for the Helsinki University Hospital, and the Cancer Foundation Finland.