HPV Association and the Increasing Incidence of Unknown Primary Head-and-Neck Squamous Cell Carcinoma: Epidemiology and Prevention

Abstract

Purpose/Objective(s)Unknown primary head and neck squamous cell carcinoma (SCCUPS) typically has a favorable prognosis. It is suspected that the historical good outcome is a reflection of a high percentage of previously unrecognized HPV (Human papillomavirus) association. It is unknown if the incidence of unknown primary carcinoma of the head and neck is rising at a rate similar to that of HPV-associated oropharynx cancer.Materials/MethodsThe institutional databases of SCCUPS from 1990 - 2013 of two tertiary care cancer centers (Fox Chase Cancer Center, Philadelphia, PA and University of Pittsburgh Medical Center) were combined. To be assigned a diagnosis of unknown primary squamous cell carcinoma all patients were required to have: 1.) pathologically proven squamous cell carcinoma in a neck lymph node, 2.) cross sectional imaging that failed to demonstrate a mucosal primary, and 3.) a negative flexible scope examination +/- directed biopsies and/or tonsillectomy. A subset of patients underwent lingual tonsillectomy, in an effort to identify the primary. HPV status was determined by immunohistochemistry (IHC) using antibody against p16 (G175-405, BD Pharmingen, USA). A positive test was defined as intermediate/strong nuclear and cytoplasmic staining in ≥ 70% of cells. Incidence rates were calculated by linear regression. Prevalence of HPV status as a function of time of diagnosis was calculated.ResultsUnknown primary carcinoma of the head and neck was diagnosed 175 times at the two institutions during the designated time frame. N stage distribution was: N1 (n = 40, 23%); N2 (n = 108, 62%); N3 (n = 27, 15%). An overwhelming majority of cases were diagnosed in the year 2000 or later (n = 144, 83%). Assignment of a diagnosis of squamous carcinoma of unknown primary exhibited linear growth since 1990 at the two institutions, with an average of 6.6 additional cases per additional 10 years, with unabated increases through the last complete year of data in 2012. A total of 126 (72%) of patients have had samples tested for HPV, almost all of which (n = 115, 91%) were treated in 2000 or later. Among those with a known HPV status, 95 (75%) were determined to be HPV associated tumors.ConclusionsThe majority of patient diagnosed with SCCUPS are p16+, indicative of HPV association. Our date demonstrate that the incidence of SCCUPS is increasing at a rate consistent with that of HPV associated oropharynx cancer. Prospective study of toxicity mitigation for this good prognosis disease indicated. Purpose/Objective(s)Unknown primary head and neck squamous cell carcinoma (SCCUPS) typically has a favorable prognosis. It is suspected that the historical good outcome is a reflection of a high percentage of previously unrecognized HPV (Human papillomavirus) association. It is unknown if the incidence of unknown primary carcinoma of the head and neck is rising at a rate similar to that of HPV-associated oropharynx cancer. Unknown primary head and neck squamous cell carcinoma (SCCUPS) typically has a favorable prognosis. It is suspected that the historical good outcome is a reflection of a high percentage of previously unrecognized HPV (Human papillomavirus) association. It is unknown if the incidence of unknown primary carcinoma of the head and neck is rising at a rate similar to that of HPV-associated oropharynx cancer. Materials/MethodsThe institutional databases of SCCUPS from 1990 - 2013 of two tertiary care cancer centers (Fox Chase Cancer Center, Philadelphia, PA and University of Pittsburgh Medical Center) were combined. To be assigned a diagnosis of unknown primary squamous cell carcinoma all patients were required to have: 1.) pathologically proven squamous cell carcinoma in a neck lymph node, 2.) cross sectional imaging that failed to demonstrate a mucosal primary, and 3.) a negative flexible scope examination +/- directed biopsies and/or tonsillectomy. A subset of patients underwent lingual tonsillectomy, in an effort to identify the primary. HPV status was determined by immunohistochemistry (IHC) using antibody against p16 (G175-405, BD Pharmingen, USA). A positive test was defined as intermediate/strong nuclear and cytoplasmic staining in ≥ 70% of cells. Incidence rates were calculated by linear regression. Prevalence of HPV status as a function of time of diagnosis was calculated. The institutional databases of SCCUPS from 1990 - 2013 of two tertiary care cancer centers (Fox Chase Cancer Center, Philadelphia, PA and University of Pittsburgh Medical Center) were combined. To be assigned a diagnosis of unknown primary squamous cell carcinoma all patients were required to have: 1.) pathologically proven squamous cell carcinoma in a neck lymph node, 2.) cross sectional imaging that failed to demonstrate a mucosal primary, and 3.) a negative flexible scope examination +/- directed biopsies and/or tonsillectomy. A subset of patients underwent lingual tonsillectomy, in an effort to identify the primary. HPV status was determined by immunohistochemistry (IHC) using antibody against p16 (G175-405, BD Pharmingen, USA). A positive test was defined as intermediate/strong nuclear and cytoplasmic staining in ≥ 70% of cells. Incidence rates were calculated by linear regression. Prevalence of HPV status as a function of time of diagnosis was calculated. ResultsUnknown primary carcinoma of the head and neck was diagnosed 175 times at the two institutions during the designated time frame. N stage distribution was: N1 (n = 40, 23%); N2 (n = 108, 62%); N3 (n = 27, 15%). An overwhelming majority of cases were diagnosed in the year 2000 or later (n = 144, 83%). Assignment of a diagnosis of squamous carcinoma of unknown primary exhibited linear growth since 1990 at the two institutions, with an average of 6.6 additional cases per additional 10 years, with unabated increases through the last complete year of data in 2012. A total of 126 (72%) of patients have had samples tested for HPV, almost all of which (n = 115, 91%) were treated in 2000 or later. Among those with a known HPV status, 95 (75%) were determined to be HPV associated tumors. Unknown primary carcinoma of the head and neck was diagnosed 175 times at the two institutions during the designated time frame. N stage distribution was: N1 (n = 40, 23%); N2 (n = 108, 62%); N3 (n = 27, 15%). An overwhelming majority of cases were diagnosed in the year 2000 or later (n = 144, 83%). Assignment of a diagnosis of squamous carcinoma of unknown primary exhibited linear growth since 1990 at the two institutions, with an average of 6.6 additional cases per additional 10 years, with unabated increases through the last complete year of data in 2012. A total of 126 (72%) of patients have had samples tested for HPV, almost all of which (n = 115, 91%) were treated in 2000 or later. Among those with a known HPV status, 95 (75%) were determined to be HPV associated tumors. ConclusionsThe majority of patient diagnosed with SCCUPS are p16+, indicative of HPV association. Our date demonstrate that the incidence of SCCUPS is increasing at a rate consistent with that of HPV associated oropharynx cancer. Prospective study of toxicity mitigation for this good prognosis disease indicated. The majority of patient diagnosed with SCCUPS are p16+, indicative of HPV association. Our date demonstrate that the incidence of SCCUPS is increasing at a rate consistent with that of HPV associated oropharynx cancer. Prospective study of toxicity mitigation for this good prognosis disease indicated.