Factors Influencing the Outcome of Head and Neck Cancer of Unknown Primary (HNCUP)

Abstract

Background: This study on patients with head and neck cancer of unknown primary (HNCUP) assesses the impact of surgical and non-surgical treatment modalities and the tumour biology on the oncological outcome. Methods: A total of 80 patients with HNCUP (UICC I–IV) were treated with simultaneous neck dissection followed by adjuvant therapy, between 1 January 2007 and 31 March 2020. As the primary objective, the influence of treatment modalities on the overall survival (OS), the disease-specific survival (DSS) and the progression-free survival (PFS) were analysed in terms of cox regression and recursive partitioning. The tumour biology served as secondary objectives. Results: The 5-year OS for the entire cohort was 67.7%, (95% CI: 54.2–81.2%), the 5-year DSS was 82.3% (72.1–92.5%) and the 5-year PFS was 72.8% (61.8–83.8%). Cox regression revealed that patients undergoing adjuvant radiotherapy only had a four times higher risk to die compared to patients receiving chemoradiation therapy (HR = 4.45 (1.40; 14.17), p = 0.012). The development of distant metastases had a significantly negative impact on OS (HR = 8.24 (3.21–21.15), p < 0.001) and DSS (HR = 23.79 (6.32–89.56), p < 0.001). Recursive portioning underlined the negative influence of distant metastases on OS (3.2-fold increase in death probability) and DSS (4.3-fold increase in death probability), while an UICC stage of IVb increased the risk for further progression of the disease by a factor of 2. Conclusions: The presence of distant metastases as well as adjuvant treatment with radiation without concomitant chemotherapy, were among others, significant predictors for the overall survival of HNCUP patients, with distant metastases being the most significant predictor.

Head and neck cancers of unknown primary: A diagnostic and therapeutic challenge

“…Squamous cell carcinoma (SCC) is the most frequently incriminated in the histopathology of head and neck CUP, its frequency being between 53% and 77% 9,10 . Of these, approximately 58% represent the common form of SCC, 15% being represented by adenocarcinomas, undifferentiated carcinomas, seromucous, basaloid or papillary carcinomas 10,11 .…”

“…Also, the choice of radiotherapy as the only therapy in cN2, N3 cases seems to be associated with a poor prognosis in terms of survival compared to multimodal chemotherapy treatment or associated with surgery 9,48 .…”

“…The data reported in the specialized literature claim that up to 75% of head and neck cancers of unknown primary are squamous cell carcinomas 3,4,6 , in 45% of cases the primary tumor being identified at the level of the palatine tonsil fossa and in 44% at the level of the tongue base 7,8 . However, the rate of undetected primary tumor can vary between 5% and 50% 9 .…”

Understanding the Role of Human Papillomavirus in Head and Neck Cancer of Unknown Primary: A Systematic Review

“…Prognostic implications of HPV in the context of HNCUP are, perhaps, the point that brings up the most controversy within studies. Some authors did not find any difference in the prognosis of patients regarding HPV status [ 8 , 10 , 17 , 19 ], while some did, and even more so, suggested the possibility of de-intensification of treatment for this patient group [ 9 , 14 , 16 , 25 ]. Axelsson et al, specifically, reported that curatively treated HNCUP has a good survival, with an overall five-year survival rate of 82%, and found that p16 positivity is associated with significantly longer survival and a lower risk of tumor recurrence [ 8 ].…”

“…Other studies highlight that the N stage is a significant prognostic factor for overall survival in patients with HNCUP treated with curative intent [ 9 ]. In another study, the main poor prognostic factor was the development of distant metastases [ 10 ].…”