Mutagen sensitivity and risk of second cancer in younger adults with head and neck squamous cell cancer: 15-year results

Abstract

Purpose To evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate the long-term rate of SPC and the outcome with SPC. Methods A survey was made regarding SPC among 124 younger (≤ 50 years) adults with HNSCC who were enrolled in a pretreatment mutagen sensitivity investigation during 1996–2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantifying the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (> 1 b/c) or not hypersensitive (≤ 1 b/c). Results Mean follow-up time for all patients was 68 months (range: 5–288 months), and the 15-year cancer-specific survival was 15%. Twenty patients (16%) developed a SPC (15-year estimated rate: 41%), and half of them was hypersensitive. The crude rate of SPC for hypersensitive (n = 65) or not hypersensitive (n = 59) patients were 15 and 17%, respectively (p = 0.4272). The 15-year estimated rate of SPC for hypersensitive and not hypersensitive patients was 36 and 48%, respectively (p = 0.3743). Gender, UICC stages, anatomical sites of index cancer did not prove to be a significant risk factor for SPC. Forty-five percent of SPC developed after the 10-year follow-up. The 3‑year cancer-specific survival was 23% with SPC. Conclusion According to our findings, mutagen hypersensitivity was not associated with an increased SPC risk in HNSCC patients. Patients are at a lifelong risk of developing a SPC. Survival with SPC is very poor.

Factors associated with the development of second primary tumours in head and neck cancer patients

“…From a total of 829 articles obtained after deleting duplicates, 703 were excluded based on title and abstract and 126 after reading the full text (Figure 1 ). Finally, 38 articles were included in this systematic review: 36 cohort studies (Adams et al, 2019 ; Adjei Boakye et al, 2019 ; Arie et al, 2021 ; Bertolini et al, 2021 ; Bosshart et al, 2021 ; Bugter et al, 2021 ; Bukovszky et al, 2022 ; Cadoni et al, 2017 ; Chow et al, 2019 ; Feng et al, 2017 ; Guo et al, 2021 ; Harada et al, 2017 ; Ho et al, 2022 ; Hosokawa et al, 2018 ; Inoue et al, 2021 ; Iwatsubo et al, 2019 ; León et al, 2020 ; Leoncini et al, 2018 ; Li et al, 2020 ; Lin et al, 2020 ; Liu et al, 2017 ; Martel et al, 2017 ; Milliet et al, 2021 ; Min et al, 2019 ; Nishimura et al, 2021 ; Overwater et al, 2022 ; Petersen et al, 2022 ; Piersiala et al, 2020 ; Sawaf et al, 2022 ; Stepan et al, 2022 ; Su et al, 2019 ; Su et al, 2020 ; Tseng et al, 2017 ; Wang et al, 2017 ; Wang et al, 2019 ; Zhang et al, 2019 ) and 2 case‐control studies (Ni et al, 2018 ; Watanabe et al, 2017 ).…”

“…Four studies did not report the SPT location (Adjei Boakye et al, 2019 ; Cadoni et al, 2017 ; Liu et al, 2017 ; Tseng et al, 2017 ). Age and sex were variables evaluated in all studies, except in Harada et al ( 2017 ), Sawaf et al ( 2022 ), Stepan et al ( 2022 ) and Bukovsky et al ( 2022 ) (the last one evaluated sex but not age).…”

“…Thirty‐three of them were classified as having a high methodological quality (7–9 points). The remaining five studies scored 5–6 points and were therefore considered as of medium quality (Bukovszky et al, 2022 ; Ni et al, 2018 ; Piersiala et al, 2020 ; Sawaf et al, 2022 ; Watanabe et al, 2017 ).…”

“…In the selection category, the item that the studies most frequently failed to fulfil was ‘representativeness of the exposed cohort’. Thus, in most cohorts many patients (more than 10%) were excluded from the eligible population because of restrictive selection criteria including not having a ‘sufficient’ or ‘complete’ follow‐up, that is, being alive at the end follow‐up, or for reasons not provided (Bukovszky et al, 2022 ; Chow et al, 2019 ; Harada et al, 2017 ; Ho et al, 2022 ; Leoncini et al, 2018 ; Lin et al, 2020 ; Martel et al, 2017 ; Ni et al, 2018 ; Nishimura et al, 2021 ; Piersiala et al, 2020 ; Sawaf et al, 2022 ; Stepan et al, 2022 ; Su et al, 2019 ; Wang et al, 2017 ; Wang et al, 2019 ; Zhang et al, 2019 ), thus introducing a potential selection bias. Other authors did not perform an exposure description (Bertolini et al, 2021 ; Feng et al, 2017 ; León et al, 2020 ; Liu et al, 2017 ; Su et al, 2020 ), and in another study, the exposure was self‐reported (Adjei Boakye et al, 2019 ).…”

“…With regards to comparability, only 4 out of the 38 studies did not get the maximum score; three because the authors did not perform multivariate analysis (Bukovszky et al, 2022 ; Piersiala et al, 2020 ; Sawaf et al, 2022 ), and another one because they did not mention the variables included in the multivariate analysis (Watanabe et al, 2017 ).…”