Risk and outcomes for second primary human papillomavirus–related and –unrelated head and neck malignancy

Abstract

Objectives/Hypothesis To 1) examine the characteristics of patients who develop second primary malignancies (SPMs) from an index human papillomavirus (HPV)‐related head and neck squamous cell carcinoma (HNSCC) and HPV‐unrelated HNSCC and to 2) compare overall survival between those with HPV‐related and HPV‐unrelated index HNSCC among patients who develop SPM. Study Design Retrospective cohort analysis. Methods A retrospective study was conducted of 113,259 patients who were diagnosed with HNSCC from 2000 to 2014. SPM was defined as the first subsequent primary cancer occurring at least 2 months after index cancer diagnosis, and HPV‐relatedness was based on whether patients’ index HNSCC was potentially HPV‐related or HPV‐unrelated. Multivariable Fine and Gray (FG) competing‐risks regression models were used to estimate factors associated with risk of SPM by HPV‐relatedness. Among patients with SPM, an adjusted Cox proportional hazards (PH) regression model was used to assess the association between HPV‐relatedness and survival. Results Approximately 13,900 patients (12.3%) developed SPM. In the FG model, patients with HPV‐unrelated HNSCC had a 15% higher risk of developing SPM (adjusted hazard ratio: 1.15, 95% confidence interval: 1.10‐1.20) than those with potentially HPV‐related HNSCC, but the same characteristics were associated with SPM development. In the Cox PH model, patients with SPM whose index HNSCC was HPV‐unrelated had higher risk of death than those whose index HNSCC was potentially HPV‐related (adjusted hazard ratio: 1.06; 95% confidence interval: 1.02‐1.11). Conclusions Patients with HPV‐unrelated HNSCC have a higher risk of SPM development than do those with HPV‐related HNSCC. Effective secondary disease‐prevention strategies should be established to improve long‐term patient outcomes. Level of Evidence NA Laryngoscope, 129:1828–1835, 2019

The risk of second primary tumors in head and neck cancer: A systematic review

“…Thus, Morris et al reviewed 75 087 patients with HNC and found that before the 1990s, hypopharynx and oropharynx cancers carried the highest risk of SPT, since then, during the HPV era, SPT risk associated with oropharyngeal cancer has declined to the lowest risk level of any subsite. A recent retrospective study in a large cohort of HNC patients also showed that patients with HPV‐related tumors has a lower risk of development of SPTs …”

Differences in human papillomavirus (HPV) vaccine uptake by nativity status among men aged 18–34 years

“…Oncogenic HPV subtypes are thought to be responsible for more than 90% of anal, 70% of oropharynx, and 60% of penile cancers (National Vaccine Advisory Committee, 2016, World Health Organization, 2016). HPV infection is not only associated with primary cancers but are also attributable to second primary cancers (Adjei Boakye et al, 2018b, Adjei Boakye et al, 2018c, Adjei Boakye et al, 2018a, Adjei Boakye et al, 2019). More than 40% of all HPV-related cancers in the US occur in men (Viens et al, 2016).…”

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 ).…”

“…The most frequent SPT sites analysed were oesophagus ( n = 22) and lung ( n = 19). 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).…”

“…Sex was found to be a risk factor for developing a SPT in seven articles, with six of them showing that men had a higher risk than women (Adjei Boakye et al, 2019 ; Ho et al, 2022 ; Hosokawa et al, 2018 ; León et al, 2020 ; Min et al, 2019 ; Zhang et al, 2019 ). Leoncini et al ( 2018 ) found a higher risk in women for SPTs located in the region of head and neck [HR: 1.54 (95% CI: 1.01–2.35)] or lung [HR: 4.29 (95% CI: 2.24–8.23)] but not when the risk was evaluated combining these and other locations.…”