Statin use and head and neck squamous cell carcinoma outcomes

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a morbid cancer with poor outcomes. Statins possess anticancer properties such as immunomodulatory and anti‐inflammatory effects. The objective of our study is to identify the association between statin use among untreated HNSCC patients and overall death, disease‐specific death and recurrence. HNSCC patients were recruited to participate in the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (SPORE) from 2003 to 2014. Statin use data were collected through medical record review. Participants were considered a statin user if they used a statin at or after diagnosis. Outcome data were collected through medical record review, Social Security Death Index or LexisNexis. Our analytic cohort included 1638 participants. Cox proportional hazard models were used to estimate the association between ever statin use and HNSCC outcomes. Statin use was seen in 36.0% of participants. We observed a statistically significant inverse association between ever using a statin and overall death (HR = 0.75, 95% CI = 0.63‐0.88) and HNSCC‐specific death (HR = 0.79, 95% CI = 0.63‐0.99) and a nonstatistically significant inverse association for recurrence (HR = 0.85, 95% CI = 0.70‐1.04). When investigating the association between statin use and HNSCC outcomes utilizing interaction terms between statin use and human papillomavirus (HPV), statistically significant interactions for HNSCC‐specific death and recurrence were identified (HNSCC‐specific death: HPV‐positive HR = 0.41, 95% CI = 0.21‐0.84; HPV‐negative HR = 1.04, 95% CI = 0.71‐1.51; p‐int=0.02; recurrence: HPV‐positive HR = 0.49, 95% CI = 0.29‐0.84; HPV‐negative HR = 1.03, 95% CI = 0.74‐1.43; p=int‐0.02). Statin use may be protective for adverse outcomes in HNSCC patients, particularly those with HPV‐positive disease. If true, these findings could have a meaningful impact on tertiary prevention for this cancer.

The association between inflammatory biomarkers and statin use among patients with head and neck squamous cell carcinoma

“…Our recently published study found that statins were protective for HNSCC outcomes, but this protective association was observed only among patients whose tumors were HPV-positive. 19 The findings from this manuscript support that the inverse association between statin use and outcomes among HPV-positive HNSCC previously reported by our group may be due to an effect of statins on TILs in patients with HPV-positive tumors. 19 The inflammatory and immunomodulatory effects of cancer are not clearly directional by cell type.…”

“…Based on our previous research, we observed an association between statin use and HNSCC outcomes, but only among patients whose disease was HPV-positive. 19 We therefore wanted to assess if effect modification by HPV status was present (HPV-positive, HPV-negative, HPV status invalid/missing) for the statin-inflammatory marker associations. Statistical interaction was evaluated using the likelihood ratio test.…”

Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer

“… 6 A large single-institution retrospective study showed similar results. 7 When subgroup analyses were done to assess the effects of HPV status with HNSCC, overall survival was increased for patients taking a statin who were HPV positive or negative, while disease-specific survival was increased by statins only in patients with HPV-positive disease. 7 In a retrospective study using the SEER Medicare database, Gupta et al classified patients with HNSCC as having hyperlipidemia plus using a statin, having hyperlipidemia but not using a statin, or not having hyperlipidemia.…”

“… 7 When subgroup analyses were done to assess the effects of HPV status with HNSCC, overall survival was increased for patients taking a statin who were HPV positive or negative, while disease-specific survival was increased by statins only in patients with HPV-positive disease. 7 In a retrospective study using the SEER Medicare database, Gupta et al classified patients with HNSCC as having hyperlipidemia plus using a statin, having hyperlipidemia but not using a statin, or not having hyperlipidemia. Patients with hyperlipidemia who were taking a statin had increased overall and disease-specific survival versus those with hyperlipidemia not taking a statin and those without hyperlipidemia.…”

“…6 A large single-institution retrospective study showed similar results. 7 When subgroup analyses were done to assess the effects of HPV status with HNSCC, overall…”