Second Primary Malignancy Risk Doubled After Head and Neck Cancer

By Will Boggs MD

NEW YORK (Reuters Health) - The risk of second primary malignant neoplasm (SPMN) doubles after a first head and neck squamous cell carcinoma (HNSCC), especially when the site of the first cancer is not typically associated with malignancies due to human papillomavirus (HPV), according to a retrospective study.

"SPMN incidence is high among all HNSCC patients, but the incidence is more pronounced among those with smoking-related HNSCCs," Dr. Eric Adjei Boakye from Saint Louis University Center for Health Outcomes Research in Missouri told Reuters Health by email.

"Even though HNSCCs from HPV have been increasing at a higher rate (about 225% over the last three decades) and HNSCCs from smoking have been decreasing due to a decrease in smoking prevalence in the U.S., patients with smoking-related HNSCCs still develop SPMNs at higher rates," he said. "This indicates that smoking may be the driver of the second cancers among HNSCC patients."

Previous studies have found an elevated risk of developing a SPMN of the lung, esophagus, and head and neck sites after a first HNSCC, but they have not examined the incidents and sites of SPMNs stratified by HNSCC etiology.

Dr. Boakye's team used data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) 18 database to quantify the risk of SPMN among patients with a first HPV-associated HNSCC versus a first non-HPV-associated HNSCC.

Among 109,512 patients with first HNSCC, 12.3% developed SPMN, including 9.6% of patients with a first potentially HPV-associated HNSCC and 14.0% of patients with a first non-HPV-associated HNSCC, according to the July 19 JAMA Otolaryngology-Head and Neck Surgery online report.

This corresponds to a 2.07-fold increased risk, compared with the general population, and an excess of 164.3 cases per 10,000 patient-years.

Both the magnitude of the increased risk and the excess absolute risk were significantly greater among patients with non-HPV-associated HNSCC (2.16-fold increased risk and 193.9 excess cases per 10,000 patient-years) than among patients with HPV-associated HNSCC (88% increased risk and 116.1 excess cases per 10,000 patient-years).

"The lower relative risk and absolute excess among patients with a first potentially HPV-associated HNSCC could be explained by the fact that most patients with HPV-positive SCC tend to have better prognosis and are less likely to use tobacco and alcohol," the researchers note.

Among patients with HPV-associated and non-HPV-associated HNSCC, the excess burden of disease was highest for lung and bronchus, followed by tongue, gum and other oral sites, and esophagus.

Both were also associated with an increased risk of thyroid cancer, and first non-HPV-associated HNSCC was also associated with an increased risk of colorectal cancer and cancers of the liver, stomach, and bladder.

"These findings could be helpful when deciding whether or not to offer smoking cessation," Dr. Boakye said. "Healthcare providers, especially oncologists should actively discuss smoking-cessation programs with their patients if they have had a history of smoking. Some patients have the mindset that since they have already developed cancer, it is okay to keep smoking! So, it is not uncommon (and this has been shown even in one of our previous studies) that many patients continue to smoke even after being diagnosed with the index HNSCC."

"HNSCC survivors should be educated that smoking not only causes the first or primary cancer, but not quitting could predispose to second and perhaps (not assessed in study) more cancers," he said. "In addition, providers should continue to screen HNSCC patients for SPMNs since the incidence is very high, especially if a patient has had a history of tobacco use. I think smoking cessation in general (not only for patients already with cancer) could be cost-effective in reducing both primary and subsequent cancers in the country."

"Future studies should use data with actual HPV status and smoking status to replicate this study," Dr. Boakye said. "This is because we used the SEER cancer database which does not provide information about smoking/tobacco history or HPV-tumor status. As a result, we used anatomic subsites that are well established for HPV-associated tumors to designate HPV status. This means that our incidence among HPV-related HNSCC may be overestimated, since many of those patients categorized as HPV-related might have had a history of smoking also."

Dr. Stefania Boccia from Universita Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli, Rome, Italy, who recently reviewed clinical features and prognostic factors in patients with HNSCC, told Reuters Health by email, "I found most interesting the fact that patients with HPV-associated head and neck cancer (HNC) seem to have a lower risk of developing a second primary malignant neoplasm, compared to patients with non-HPV-associated HNC."

"The main findings of this study are helpful in order to identify the anatomical sites of HNC that are at higher risk of developing a second primary cancer, which is the leading cause of death in patients with primary HNC," she said. "Close monitoring of these patients is necessary in order to detect the second primary cancer early."

SOURCE: https://bit.ly/2Lrq08g

JAMA Otolaryngol Head Neck Surg 2018.

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