Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study
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Among the metastasis patterns of head and neck squamous cell carcinoma (HNSCC), intracranial spread is a rare but dreaded event. To date only very few cases have been reported and clinical and molecular data are sparse. We screened our archives for HNSCC patients from 1992 to 2005 who were diagnosed with brain metastases (BM). For retrospective analysis, all clinico-pathological data including disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) were compiled. Additionally, we assessed the mutational status of the TP53 gene and the prevalence of HPV serotypes by PCR and Sanger sequencing. Immunohistochemistry was applied to detect p16INK4A expression levels as surrogate marker for HPV infection. The prevalence rate of BM in our cohort comprising 193 patients with advanced HNSCC was 5.7 %. Of 11 patients with BM, 3 were female and 9 were male. Seven of the primary tumors were of oropharyngeal origin (OPSCC). LPFS of the cohort was 11.8 months, DFS was 12.1 months and OS was 36.0 months. After the diagnosis of BM, survival was 10.5 months. Five tumors showed a mutation in the TP53 gene, while five of the seven OPSCC tumors had a positive HPV status displaying infection with serotype 16 in all cases. Compared with patients who harbored TP53wt/HPV-positive tumors, patients with TP53 mutations showed a poor prognosis. Compared with the whole cohort, the interval between diagnosis of the primary and the detection of BM was prolonged in the HPV-infected OPSCC subgroup (26.4 vs. 45.6 months). The prognosis of HNSCC patients with BM is poor. In our cohort, most tumors were OPSCC with the majority being HPV positive. Our study points toward a putatively unusual metastatic behavior of HPV-positive OPSCC.
KeywordsHNSCC Oropharynx HPV Brain Distant metastasis
Conflict of interest
The authors declare no conflict of interest.
- 4.Dayyani F, Etzel CJ, Liu M et al (2010) Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol 29:2–15Google Scholar
- 14.Huang SH, Perez-Ordonez B, Liu FF, Waldron J, Ringash J, Irish J, Cummings B, Siu LL, Kim J, Weinreb I, Hope A, Gullane P, Brown D, Shi W, O‘Sullivan B (2012) Atypical clinical behavior of p16-confirmed HPV-related oropharyngeal squamous cell carcinoma treated with radical radiotherapy. Int J Radiat Oncol Biol Phys 82(1):276–283PubMedCrossRefGoogle Scholar
- 16.Barnes L, Eveson JW, Reichart P, Sidransky D (eds) (2005) Pathology and Genetics of Head and Neck Tumours (IARC WHO Classification of Tumours). The International Agency for Research on CancerGoogle Scholar
- 17.Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) (2009) Seventh Edition of the AJCC Cancer Staging ManualGoogle Scholar
- 18.Hristozova T, Konschak R, Stromberger C, Fusi A, Liu Z, Weichert W, Stenzinger A, Budach V, Keilholz U, Tinhofer I (2011) The presence of circulating tumor cells (CTCs) correlates with lymph node metastasis in non-resectable squamous cell carcinoma of the head and neck region (SCCHN). Ann Oncol 8:1878–1885CrossRefGoogle Scholar
- 23.Worden FP, Hooton J, Lee J, Eisbruch A, Wolf GT, Prince M, Moyer J, Teknos T, Chepeha DB, Bradford CR (2009) Association of tobacco (T) use with risk of distant metastases (DM), tumor recurrence, and death in patients (pts) with HPV-positive (+) squamous cell cancer of the oropharynx (SCCOP). J Clin Oncol 27:15sCrossRefGoogle Scholar
- 24.Maxwell JH, Kumar B, Feng FY, Worden FP, Lee JS, Eisbruch A, Wolf GT, Prince ME, Moyer JS, Teknos TN, Chepeha DB, McHugh JB, Urba SG, Stoerker J, Walline HM, Kurnit DM, Cordell KG, Davis SJ, Ward PD, Bradford CR, Carey TE (2010) Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res 16(4):1226–1235PubMedCentralPubMedCrossRefGoogle Scholar