In the Journals

Persistent HPV DNA may predict progression of certain head and neck cancers

Detection of persistent HPV DNA in oral rinses appeared associated with greater risk for disease recurrence and death among patients with HPV-positive oral and oropharyngeal squamous cell carcinoma, according to study results published in JAMA Oncology.

The results suggest HPV DNA has potential as a biomarker for progression risk and treatment response among this patient population.

“HPV, predominantly high-risk type 16, is estimated to cause approximately 22% of oropharyngeal and 5% of oral cavity squamous cell carcinomas worldwide. Survival rates are significantly higher among patients diagnosed with HPV-positive than HPV-negative oropharyngeal cancer,” Carole Fakhry, MD, MPH, associate professor of otolaryngology-head and neck surgery at Johns Hopkins School of Medicine, and colleagues wrote. “However, approximately 20% of patients diagnosed with HPV-positive oropharyngeal cancer experience cancer progression within 5 years. National Comprehensive Cancer Network guidelines recommend that patients with head and neck squamous cell carcinoma undergo routine clinical surveillance for cancer recurrence.”

In the prospective, two-institution, tertiary referral center study, Fakhry and colleagues investigated associations of HPV DNA — detected through an oral rinse — with disease outcomes among 396 adults (median age, 59 years; range, 19-96; 74.5% men; 89.4% white) with recently diagnosed oropharyngeal (n = 217), oral cavity (n = 170) or unknown primary (n = 9) HNSCC. Slightly more than half of the patients (51%) had HPV-positive HNSCC.

The researchers prospectively acquired oral rinse samples by 30-second rinse and gargle with saline at diagnosis and at the conclusion of primary treatment. They also collected samples weekly during radiotherapy.

The researchers screened DNA from purified tumor and oral rinse samples for 37 HPV types, quantifying viral load by type-specific, real-time polymerase chain reaction. Cancers underwent stratification by tumor HPV status, with HPV classified as tumor type if it matched that identified in the tumor or nontumor type.

Prevalence of HPV DNA before, during and after treatment served as the study’s main outcomes. The study also evaluated associations between tumor-type and nontumor-type oral HPV DNA identification and RFS and OS.

Median follow-up by reverse Kaplan-Meier method was 2.6 years (range, 21 days to 5.5 years).

Results showed patients with HPV-positive disease had a higher prevalence of oral HPV detection at diagnosis than those with HPV-negative disease (24 of 194 [84.2%] vs. 170 of 202 [12.4%]; P < .001).

Oral HPV-16 DNA detected HPV-16-positive HNSCC with a sensitivity of 80.6% (95% CI, 74-86.1) and a specificity of 100% (95% CI, 84.5-100).

The rate of tumor-type HPV DNA detection dropped significantly during primary therapy among patients with HPV-positive tumors (OR = 0.41; 95% CI, 0.33-0.52).

Conversely, the rate of nontumor-type infections remained stable (OR = 1.01; 95% CI, 0.97-1.06). Current smokers had significantly less clearance of tumor-type HPV DNA (HR = 0.54; 95% CI, 0.32-0.93).

HPV-positive patients with ongoing detection of tumor-type HPV after treatment had significantly lower 2-year OS than those without identifiable tumor-type DNA after treatment (68% vs. 95%; adjusted HR = 6.61; 95% CI, 1.86-23.44) and significantly lower rates of RFS (55% vs. 88%; adjusted HR = 3.72; 95% CI, 1.71-8.09). Nontumor-type HPV DNA did not appear to be associated with HPV-positive or HPV-negative HNSCC.

Researchers acknowledged limitations to their study, including the typical follow-up time of about 2 years that may have underestimated associations between HPV persistence and cancer recurrence.
[for] distant metastases. Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.” – by Jennifer Byrne

Disclosures: Fakhry reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Detection of persistent HPV DNA in oral rinses appeared associated with greater risk for disease recurrence and death among patients with HPV-positive oral and oropharyngeal squamous cell carcinoma, according to study results published in JAMA Oncology.

The results suggest HPV DNA has potential as a biomarker for progression risk and treatment response among this patient population.

“HPV, predominantly high-risk type 16, is estimated to cause approximately 22% of oropharyngeal and 5% of oral cavity squamous cell carcinomas worldwide. Survival rates are significantly higher among patients diagnosed with HPV-positive than HPV-negative oropharyngeal cancer,” Carole Fakhry, MD, MPH, associate professor of otolaryngology-head and neck surgery at Johns Hopkins School of Medicine, and colleagues wrote. “However, approximately 20% of patients diagnosed with HPV-positive oropharyngeal cancer experience cancer progression within 5 years. National Comprehensive Cancer Network guidelines recommend that patients with head and neck squamous cell carcinoma undergo routine clinical surveillance for cancer recurrence.”

In the prospective, two-institution, tertiary referral center study, Fakhry and colleagues investigated associations of HPV DNA — detected through an oral rinse — with disease outcomes among 396 adults (median age, 59 years; range, 19-96; 74.5% men; 89.4% white) with recently diagnosed oropharyngeal (n = 217), oral cavity (n = 170) or unknown primary (n = 9) HNSCC. Slightly more than half of the patients (51%) had HPV-positive HNSCC.

The researchers prospectively acquired oral rinse samples by 30-second rinse and gargle with saline at diagnosis and at the conclusion of primary treatment. They also collected samples weekly during radiotherapy.

The researchers screened DNA from purified tumor and oral rinse samples for 37 HPV types, quantifying viral load by type-specific, real-time polymerase chain reaction. Cancers underwent stratification by tumor HPV status, with HPV classified as tumor type if it matched that identified in the tumor or nontumor type.

Prevalence of HPV DNA before, during and after treatment served as the study’s main outcomes. The study also evaluated associations between tumor-type and nontumor-type oral HPV DNA identification and RFS and OS.

Median follow-up by reverse Kaplan-Meier method was 2.6 years (range, 21 days to 5.5 years).

Results showed patients with HPV-positive disease had a higher prevalence of oral HPV detection at diagnosis than those with HPV-negative disease (24 of 194 [84.2%] vs. 170 of 202 [12.4%]; P < .001).

Oral HPV-16 DNA detected HPV-16-positive HNSCC with a sensitivity of 80.6% (95% CI, 74-86.1) and a specificity of 100% (95% CI, 84.5-100).

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The rate of tumor-type HPV DNA detection dropped significantly during primary therapy among patients with HPV-positive tumors (OR = 0.41; 95% CI, 0.33-0.52).

Conversely, the rate of nontumor-type infections remained stable (OR = 1.01; 95% CI, 0.97-1.06). Current smokers had significantly less clearance of tumor-type HPV DNA (HR = 0.54; 95% CI, 0.32-0.93).

HPV-positive patients with ongoing detection of tumor-type HPV after treatment had significantly lower 2-year OS than those without identifiable tumor-type DNA after treatment (68% vs. 95%; adjusted HR = 6.61; 95% CI, 1.86-23.44) and significantly lower rates of RFS (55% vs. 88%; adjusted HR = 3.72; 95% CI, 1.71-8.09). Nontumor-type HPV DNA did not appear to be associated with HPV-positive or HPV-negative HNSCC.

Researchers acknowledged limitations to their study, including the typical follow-up time of about 2 years that may have underestimated associations between HPV persistence and cancer recurrence.
[for] distant metastases. Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.” – by Jennifer Byrne

Disclosures: Fakhry reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.