Abstract
This study uses SEER data to evaluate the survival outcomes of oropharyngeal small-cell carcinoma, compared with squamous cell carcinoma.
Small-cell carcinoma (SmCC) is a neuroendocrine malignant neoplasm that usually occurs in the lungs. Oropharyngeal SmCC is a rare entity, with the current literature limited to case reports and small case series. Many of these reports suggest that it is a highly aggressive disease with dismal outcomes. However, it is difficult to draw conclusions about the survival outcomes of oropharyngeal SmCC based on the existing literature. The goal of our study was to evaluate the survival outcomes of oropharyngeal SmCC, compared with squamous cell carcinoma (SqCC).
Methods
This study was exempt from review by the Stanford University Institutional Review Board due to its use of deidentified public data. The study cohort included adult patients who received a diagnosis of oropharyngeal SmCC or SqCC between 1973 and 2013, identified in the Surveillance, Epidemiology, and End Results (SEER) 18 Database. Disease stage was recorded using SEER historic stage, classified into the following: “localized,” “regional,” and “distant.” Race was recorded in the SEER database as “white,” “black,” or “other.”
The SEER computer software (SEER*Stat, version 8.3.2) was used to extract data from the SEER database and to compute disease incidence. The statistical analysis was performed using IBM SPSS, version 23 (IBM). Survival analysis was performed using Kaplan-Meier analysis. The outcome variables were overall cumulative survival (OS) and disease-specific cumulative survival (DSS). A Cox proportional hazards regression model was used for multivariable analysis. Candidate covariates were entered a priori into the model. An estimate was considered statistically significant at α = .05.
Results
The SEER database identified 45 patients with oropharyngeal SmCC, compared with 40 571 patients with SqCC. The incidence of oropharyngeal SmCC was 0.003 per 100 000. Patient characteristics are shown in the Table. Patients with oropharyngeal SmCC were more likely to present with distant disease (odds ratio, 3.76; 95% CI, 2.04-6.96) and less likely to present with regional disease (odds ratio, 0.34; 95% CI, 0.18-0.62).
Table. Patient Characteristics.
| Variable | Small-Cell Carcinoma (n = 45) |
Squamous Cell Carcinoma (n = 40 571) |
Difference (95% CI) |
|---|---|---|---|
| Age, mean (SD), y | 60.2 (13.2) | 59.5 (11.0) | 0.67 (−2.55 to 3.89) |
| Female, No. (%) | 11 (24) | 8441 (21) | −3.6% (−16.7% to 9.4%) |
| Race, No. (%) | |||
| White | 41 (91) | 34 248 (84) | −6.7% (−15.5% to 2.1%) |
| Black | 4 (9) | 4906 (12) | 3.2% (−5.5% to 11.9%) |
| Site, No. (%) | |||
| Tongue base | 24 (53) | 16 200 (40) | −13.4% (−28.6% to 1.8%) |
| Soft palate | 0 | 2537 (6) | 6.3% (6.0% to 6.5%) |
| Tonsil | 15 (33) | 18 776 (46) | 13.0% (−1.4% to 27.3%) |
| Pharyngeal wall | 0 | 692 (2) | 1.7% (1.6% to 1.8%) |
| Other | 6 (13) | 2374 (6) | −7.4% (−17.8% to 2.8%) |
| Regional disease, No. (%) | 18 (40) | 27 434 (68) | 27.6% (10.2% to 51.9%) |
| Distant disease, No. (%) | 19 (42) | 7317 (18) | 24.2% (−43.6% to −11.7%) |
| Surgical resection, No. (%) | 9 (27) | 15 254 (42) | 14.2% (−1.8% to 30.3%) |
| Radiotherapy, No. (%) | 29 (67) | 32 606 (82) | 14.7% (0% to 29.2%) |
Small-cell carcinoma was associated with worse OS (5-year OS, 19.5% vs 49.5%; difference, 30.0%; 95% CI, 17.1%-42.9%) and DSS (5-year DSS, 24.1% vs 58.3%; difference, 34.2%; 95% CI, 19.1%-49.3%) compared with SqCC (Figure). On multivariable analysis, SmCC was associated with worse OS (hazard ratio, 1.67; 95% CI, 1.02-2.73) and DSS (hazard ratio, 1.80; 95% CI, 1.06-3.03), after adjustment for age, sex, race, year of diagnosis, site, distant disease, regional disease, surgical resection of primary site, treatment with neck dissection, radiation therapy, and lack of treatment.
Figure. Overall Survival as a Function of Histologic Type.
Patients with small-cell carcinoma had worse survival than patients with squamous cell carcinoma.
Discussion
To our knowledge, this study is the largest study to date of patients with oropharyngeal SmCC. We show that oropharyngeal SmCC was more likely to present with distant disease, less likely to present with regional disease, and was associated with poor OS and DSS, compared with oropharyngeal SqCC. Given the rarity of the disease, the literature on oropharyngeal SmCC is mostly limited to case reports and small case series. The earliest documented case series comes from a single institution’s 24-year experience published in 1972. All 5 patients died of disease, with a follow-up of 5 to 180 months.
Bishop and Westra published the largest series of primary oropharyngeal SmCC, with 9 cases. Seven of the 9 patients died of disease, while the remaining 2 showed no evidence of disease at 5 and 20 months of follow-up. Another relatively large case series by Kraft et al reported on 8 patients with oropharyngeal SmCC. Of the 6 patients with available clinical data, only 1 patient remained disease-free at 25 months follow-up.
The poor outcomes for SmCC suggest the need for more aggressive therapy in this type of oropharyngeal cancer, especially given current trends of de-escalation of therapy for oropharyngeal cancer.
References
- 1.Koss LG, Spiro RH, Hajdu S. Small cell (oat cell) carcinoma of minor salivary gland origin. Cancer. 1972;30(3):737-741. [DOI] [PubMed] [Google Scholar]
- 2.Bishop JA, Westra WH. Human papillomavirus-related small cell carcinoma of the oropharynx. Am J Surg Pathol. 2011;35(11):1679-1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kraft S, Faquin WC, Krane JF. HPV-associated neuroendocrine carcinoma of the oropharynx: a rare new entity with potentially aggressive clinical behavior. Am J Surg Pathol. 2012;36(3):321-330. [DOI] [PubMed] [Google Scholar]
- 4.Bawa R, Wax MK. Small cell carcinoma of the tonsil. Otolaryngol Head Neck Surg. 1995;113(3):328-333. [DOI] [PubMed] [Google Scholar]
- 5.Mineta H, Miura K, Takebayashi S, et al. . Immunohistochemical analysis of small cell carcinoma of the head and neck: a report of four patients and a review of sixteen patients in the literature with ectopic hormone production. Ann Otol Rhinol Laryngol. 2001;110(1):76-82. [DOI] [PubMed] [Google Scholar]
- 6.Wang H-Y, Zou J, Zhou G-Y, Yan J-Q, Liu S-X. Primary small cell neuroendocrine carcinoma of the tonsil: a case report and review of the literature. Int J Clin Exp Pathol. 2014;7(5):2678-2682. [PMC free article] [PubMed] [Google Scholar]