Post-treatment persistence of oral HPV in HNSCC predicts recurrence, death

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.