April 10, 2016
2 min read

Increased frequency of unknown primary SCC linked to HPV–positive disease

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The occurrence of HPV–positive unknown primary squamous cell carcinoma of the head and neck has significantly increased in recent years, according to the results of a retrospective study.

HPV–positive unknown primary squamous cell carcinoma (UPSCC) appeared most prevalent among younger men.

UPSCC of the head and neck is comparatively rare, accounting for approximately 4% of squamous cell carcinomas. Trends, frequency and detection rates of UPSCCs have not been studied in the context of HPV tumor status.

Carole Fakhry, MD, MPH
Carole Fakhry

Carole Fakhry, MD, MPH, associate professor of oncology and otolaryngology–head and neck surgery at Johns Hopkins School of Medicine, and colleagues conducted a retrospective study to observe the frequency of UPSCC over time, and to evaluate the proportion of UPSCCs that are HPV positive.

Researchers accessed a case series of 84 patients (mean age, 57.3 years; range, 29-80; 88.1% men) with UPSCC treated at Johns Hopkins Hospital between January 2005 and June 2014. They determined HPV tumor status through p16 immunohistochemical analysis or through high-risk HPV DNA in situ hybridization, when clinically available.

The researchers observed an increase in the frequency of UPSCC over time (P for trend = .01). The trend appeared significantly higher during the most recent calendar periods (14 cases during 2005-2008 vs. 39 cases during 2012-2014; P = .03).

A total of 90.7% of patients (n = 69) had HPV–positive tumors. These patients appeared more likely to be men (91% vs. 42.9%; P = .005) and younger (56.1 years vs. 67.7 years; P = .002) than patients with HPV–negative tumors.

The researchers detected the primary tumor site in over half the patients (59.3%), 95.7% of whom were HPV positive. All of the primary tumors were found in the oropharynx.

When researchers evaluated the trends in detection of the primary tumor over time, they observed an insignificant increase in the detection rate from 50% in 2005 to 2008 to 64.9% in 2012 to 2014.

The researchers then calculated the proportion of primary tumors identified before and after transoral robotic surgery (TORS) lingual tonsillectomy became available in 2011. Fewer primary tumor sites were identified prior to the availability of TORS (53.8% vs. 64.3%); however, this difference did not reach statistical significance.

“The findings of this study indicate an increasing frequency of UPSCCs and that most of these cases are HPV positive,” Fakhry and colleagues wrote. “It is likely that the increase in HPV–related tumors is driving the increase in UPSCC. HPV–positive UPSCCs differ from HPV–negative UPSCCs by clinicodemographic characteristics.” – by Cameron Kelsall


Motz K, et al. JAMA Otolaryngol Head Neck Surg. 2016;doi:10.1001/jamaoto.2015.3228.

Disclosure: The researchers report no relevant financial disclosures.