Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection

Abstract

BackgroundHead and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival.MethodsA search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992–2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining.ResultsSixty-eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16-negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5-year survival rates, respectively. The overall and disease-free 5-year survival rates for all patients in the study were 82 and 74%.ConclusionsCuratively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or (chemo) radiation showed similar survival rates.

Impact of the 8th edition of the UICC TNM classification on staging and survival in patients with neck metastases of unknown primary tumor

“…Keller et al [58] reported on even more pronounced survival differences in p16 positive compared to p16 negative patients (5y OS 92% vs 30% and 5y DSS 92% vs 60%) [58]. Similar results were demonstrated by Jensen et al [57], Schroeder et al [27] and Axelsson et al [64], whereas Tribius et al [55] and Dixon et al [65] did not find any survival difference. In contrast to some [1,2,27,[66][67][68] but in line with other reports [54,56] nodal stage did not have an impact on survival in our cohort.…”

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

“…68 Adjuvant CRT was administered in four patients (three RT and one CRT) in case of positive margins, extranodal extension, multiple positive lymph nodes, perineural invasion, or lymphovascular invasion. 24 Outcome analysis demonstrated similar 2-, 5-, and 10-year OS (93%, 89%, and 89% vs 90%, 90%, and 80% in the two groups, respectively). 68 Neck dissection is a common practice but should be reconsidered in the light of RT advances as outcomes were independent of neck dissection in some studies.…”

“…6,16,17,20 The male predominance correlates with the ease of female-to-male HPV transmission which is precipitated by the high number of sexual partners and oral sex encounters. 16,17,19,20,[22][23][24] However, one retrospective analysis of a small series of patients showed that the HPV status does not correlate with neck stage at presentation. The clinical N classification at diagnosis is usually N2/N3 (11%-95%).…”

“…The assessment for HPV and p16 must be performed systematically on FNAC in patients with SCCUP as their positivity raises the suspicion of a primary oropharyngeal squamous cell carcinoma (OPSCC). 7,16,23,24,54 Different tools for the detection of biologically active HPV infections have been evaluated in SCCUP. 16,17,51,52 The predominant pathology in HPV-related SCCUP is the non-keratinizing basaloid squamous cell carcinoma with occasional necrosis.…”

“…16,19,24,51,57,68 In these studies, HPV-related SCCUP has a good prognosis which constitutes the backdrop for separating this entity from non-HPV-related SCCUP. 16,19,24,51,57,68 In these studies, HPV-related SCCUP has a good prognosis which constitutes the backdrop for separating this entity from non-HPV-related SCCUP.…”