Occult Primary Head and Neck Squamous Cell Carcinoma: Utility of Discovering Primary Lesions

Abstract

Objective Cancer of an unknown primary (CUP) squamous cell carcinoma metastatic to cervical lymph nodes is a challenging problem for the treating physician. Our aim is to determine if identification of the primary tumor is associated with improved oncologic outcomes and/or tumor characteristics including human papilloma virus (HPV) status. Study Design Retrospective, matched-pairs analysis contrasting 2 cohorts based upon discovery of primary lesion. Setting Tertiary teaching hospital. Subjects and Methods Records of 136 patients initially diagnosed as carcinoma of unknown primary were retrospectively reviewed (1980–2010) and divided into 2 cohorts based on discovery of the primary lesion. Primary outcome measures were overall survival and time to recurrence according to Kaplan-Meier analysis. A nested subset of 22 patients in which the primary was discovered were matched to 22 patients remaining undiscovered according to nodal stage and age. Results Discovered lesions were more likely to exhibit HPV positivity (P <.001). Matched-pairs analyses demonstrated that discovery of the primary was associated with better overall survival (HR = 0.125; 95% confidence interval [CI], 0.019–0.822; P = .030). Discovery of the primary was associated with improved cause-specific survival (HR = 0.142; 95% CI, 0.021–0.93; P = .0418) and disease-free survival (HR = 0.25; 95% CI, 0.069–0.91; P = .03). Conclusion HPV positivity is associated with discovery of the primary tumor. Discovery of the primary lesion is associated with improved overall survival, cause-specific survival, and disease-free survival in patients initially presenting as CUP in matched-pair and cohort comparison analyses.

Human papillomavirus is a favourable prognostic factor in cancer of unknown primary in the head and neck region and in hypopharyngeal cancer

“…In 1.5-9% of the cases, however, a primary tumour may not be identified, despite a systematic clinical work-up including tonsillectomy, random biopsies from the base of the tongue and nasopharynx, and magnetic resonance imaging of the head and neck (17). In such cases, the lymph node metastasis is defined as CUP of the head and neck region (10)(11)(12)(13)(14)(15)(16)(17). FNAC showing a cancer other than SCC, e.g.…”

“…Recent studies reported the prevalence of HPV DNA, p16 or both in CUP of the head and neck region (10)(11)(12)(13)(14)(15)(16)(17). The highest HPV prevalence (59-92%) was observed in patients who were not subjected to tonsillectomy or random biopsies from the base of the tongue, who were at a higher risk of missing a minute TSCC or BOTSCC (17).…”

“…It has been demonstrated that HPV-positive CUP of the head and neck region has a significantly better prognosis compared with that of HPV-negative CUP (10)(11)(12)(13)(14)(15)(16)(17). In one report, 40% of CUP cases were HPV-positive and had a 3-year overall survival (OS) rate of 80%, compared with 36.7% in the HPV-negative cases, with similar DFS (14).…”

“…Accumulating reports describe the presence of HPV DNA in several cancers of unknown primary (CUP) in the head and neck region, as well as in a minority of hypopharyngeal cancers and other non-OPSCC locations (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Notably, patients with HPV-positive tumours, particularly in CUP of the head and neck region and possibly also in hypopharyngeal cancer, tend to have a better clinical outcome compared with those with corresponding HPV-negative tumours, in whom HPV status may also have implications for diagnosis and therapy (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)27,28). However, this has not been investigated in the same detail for other cancer locations in the head and neck region, whereas reports usually compare survival between patients with HPV-positive and those with HPV-negative non-OPSCC.…”

Approach to Metastatic Carcinoma of Unknown Primary in the Head and Neck: Squamous Cell Carcinoma and Beyond

“…p16 IHC can be helpful to highlight small foci of SCC; but the expression must be strong and diffuse, as normal tonsillar crypt epithelium shows patchy p16 positivity. There is some evidence that identification of the primary site in a patient who initially presents with an unknown primary is associated with improved overall survival [29]. However, the improved survival may simply be because a primary site is more likely to be detected for HPV-related metastases that present as unknown primaries, and HPV-related SCC is known to have better outcomes than HPV-unrelated SCC.…”