In the JournalsPerspective

HCV increases risk for head and neck cancers

Hepatitis C virus infection appeared associated with an increased risk for certain nonoropharyngeal cancers and human papillomavirus-positive oropharyngeal cancer, according to results of a case–control study.

In 2009, The University of Texas MD Anderson Cancer Center opened the first clinic in the United States to manage HCV infection in patients with cancer.

“To our surprise, we saw a number of head and neck cancer patients who tested positive for the hepatitis C virus,” Harrys A. Torres, MD, associate professor of infectious disease, infection control and employee health at MD Anderson, said in a press release. “Obviously, a hepatitis C infection could impact how patients respond to their cancer therapy. We also realized that many of our hepatitis patients were excluded from clinical trials. Now that many with hepatitis C can be cured, it is important we first address and potentially cure the virus, so that they can have access to necessary cancer therapy."

Torres and colleagues reviewed the medical records of 34,545 patients with cancer tested for HCV antibodies to identify any association between HCV and head and neck cancers. Researchers also reviewed human papillomavirus (HPV) test results from biopsy reports of patients with oropharyngeal cancer.

From the overall cohort, researchers included data from 409 patients with oropharyngeal (n = 164) or nonoropharyngeal (n = 245) cancer, as well as from a control group of 694 patients with smoking-associated cancers — specifically, cancers of the lung (n = 378), esophagus (n = 168) and bladder (n = 148).

Of these 1,103 patients (median age at diagnosis, 62 years), 79.2% were white and 72.4% were men.

The prevalence of HCV seropositivity was higher in patients with oropharyngeal cancer (14%; 95% CI, 8.7-19.4) — especially among those who were HPV–positive (16.9%; 95% CI, 8.7-24.9) — and in patients with nonoropharyngeal head and neck cancer (20%; 95% CI, 14.9-25) than in the control group (6.5%; 95% CI, 4.6-8.3).

Models adjusted for factors, such as age at cancer diagnosis, sex, smoking history and alcohol consumption, showed HCV seropositivity was significantly associated with nonoropharyngeal head and neck cancer (OR = 2.85, 95% CI, 1.38-5.88) and HPV–positive oropharyngeal cancers (OR = 2.97, 95% CI, 1.31-6.76).

However, results showed that nasopharyngeal cancer was an exception to this association (OR = 1.3, 95% CI, 0.22-7.64).

Researchers acknowledged limitations to these results, including that the control group consisted of patients with cancer rather than being a cancer-free population. Torres and colleagues also noted the possibility of Berkson's bias — or different exposure rates in the control group and general population — because the HCV infection prevalence in the control group was 6% compared with 1.5% in the general population.

Although HCV has long been associated with liver cancer and non-Hodgkin lymphoma, these data are the first to show HCV also is associated with certain head and neck cancers.

“Our results add to the growing body of epidemiological evidence that HCV infection has extra-hepatic manifestations and may be associated with non–liver-related cancers,” Torres and colleagues wrote.

“What we are trying to make all understand is that this an infection that has consequences — and it's an infection we can cure,” Torres said. by Nick Andrews

Disclosure: Torres reports consultant roles with Astellas, Genentech, Gilead Science, Janssen Pharmaceuticals, Merck, Novartis, Pfizer, Theravance Biopharma and Vertex Pharmaceuticals. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Hepatitis C virus infection appeared associated with an increased risk for certain nonoropharyngeal cancers and human papillomavirus-positive oropharyngeal cancer, according to results of a case–control study.

In 2009, The University of Texas MD Anderson Cancer Center opened the first clinic in the United States to manage HCV infection in patients with cancer.

“To our surprise, we saw a number of head and neck cancer patients who tested positive for the hepatitis C virus,” Harrys A. Torres, MD, associate professor of infectious disease, infection control and employee health at MD Anderson, said in a press release. “Obviously, a hepatitis C infection could impact how patients respond to their cancer therapy. We also realized that many of our hepatitis patients were excluded from clinical trials. Now that many with hepatitis C can be cured, it is important we first address and potentially cure the virus, so that they can have access to necessary cancer therapy."

Torres and colleagues reviewed the medical records of 34,545 patients with cancer tested for HCV antibodies to identify any association between HCV and head and neck cancers. Researchers also reviewed human papillomavirus (HPV) test results from biopsy reports of patients with oropharyngeal cancer.

From the overall cohort, researchers included data from 409 patients with oropharyngeal (n = 164) or nonoropharyngeal (n = 245) cancer, as well as from a control group of 694 patients with smoking-associated cancers — specifically, cancers of the lung (n = 378), esophagus (n = 168) and bladder (n = 148).

Of these 1,103 patients (median age at diagnosis, 62 years), 79.2% were white and 72.4% were men.

The prevalence of HCV seropositivity was higher in patients with oropharyngeal cancer (14%; 95% CI, 8.7-19.4) — especially among those who were HPV–positive (16.9%; 95% CI, 8.7-24.9) — and in patients with nonoropharyngeal head and neck cancer (20%; 95% CI, 14.9-25) than in the control group (6.5%; 95% CI, 4.6-8.3).

Models adjusted for factors, such as age at cancer diagnosis, sex, smoking history and alcohol consumption, showed HCV seropositivity was significantly associated with nonoropharyngeal head and neck cancer (OR = 2.85, 95% CI, 1.38-5.88) and HPV–positive oropharyngeal cancers (OR = 2.97, 95% CI, 1.31-6.76).

However, results showed that nasopharyngeal cancer was an exception to this association (OR = 1.3, 95% CI, 0.22-7.64).

Researchers acknowledged limitations to these results, including that the control group consisted of patients with cancer rather than being a cancer-free population. Torres and colleagues also noted the possibility of Berkson's bias — or different exposure rates in the control group and general population — because the HCV infection prevalence in the control group was 6% compared with 1.5% in the general population.

Although HCV has long been associated with liver cancer and non-Hodgkin lymphoma, these data are the first to show HCV also is associated with certain head and neck cancers.

“Our results add to the growing body of epidemiological evidence that HCV infection has extra-hepatic manifestations and may be associated with non–liver-related cancers,” Torres and colleagues wrote.

“What we are trying to make all understand is that this an infection that has consequences — and it's an infection we can cure,” Torres said. by Nick Andrews

Disclosure: Torres reports consultant roles with Astellas, Genentech, Gilead Science, Janssen Pharmaceuticals, Merck, Novartis, Pfizer, Theravance Biopharma and Vertex Pharmaceuticals. Please see the full study for a list of all other researchers’ relevant financial disclosures.

    Perspective

    Barbara Ann Burtness, MD

    Barbara Ann Burtness

    Mahale and colleagues conducted a case–control study, drawing on a large population of patients with cancer and hepatitis C virus (HCV) infection followed at The University of Texas MD Anderson Cancer Center. Head and neck cancer cases (n = 409) were separated into oropharynx and nonoropharynx cases, presumably as something of a surrogate for HPV infection. This dichotomization was supported by assays for HPV or with the surrogate biomarker p16 in the 57% of oropharyngeal cancer cases, in which such testing had been performed as part of clinical work-up. Because of the very strong association of HPV–negative head and neck cancer with cumulative tobacco use, the control cases selected were patients with lung, esophageal or bladder cancers, albeit there has been a rise in esophageal adenocarcinoma in nonsmokers in recent decades. Patients with lymphoma were excluded because of the known association of hepatitis C with some forms of lymphoma. The researchers reported a strong association between seropositivity for hepatitis C and head and neck cancer.

    An important consideration is whether hepatitis C seropositivity correlates with head and neck cancer because hepatitis C can play a role in the initiation or progression of these cancers, or whether it is merely a reflection of other exposures that lead to head and neck cancer. Injection drug use remains the most important risk factor for HCV acquisition in the United States, and changes in incidence of HCV infections in younger-birth cohorts in the United States mirror changes in illegal opiate use. Other characteristics associated with HCV infection that overlap with head and neck cancer risk factors for both HPV–associated and HPV–negative head and neck cancer include alcohol use, male sex, black race, low family income, high school education or less, and a history of at least 10 lifetime sexual partners. The results of this study stood up to adjustment for a number of these factors, including birth cohort, as well as tobacco and alcohol exposure.

    Limitations of the study include use of a control group that consisted entirely of individuals with cancer rather than examining hepatitis C prevalence in patients without cancer; conduct in a country with low hepatitis C prevalence, which increases the impact of behavioral risk factors on hepatitis C acquisition and raises the likelihood of confounding when those risk factors independently lead to head and neck cancer; and the fact hepatitis C screening was not done uniformly across patient groups at MD Anderson.

    Nonetheless, this is a provocative publication, and future studies to determine if hepatitis C has a role in head and cancer carcinogenesis are warranted.


    Barbara Ann Burtness, MD
    HemOnc Today Editorial Board member
    Yale Cancer Center

    Disclosure: Burtness reports no relevant financial disclosures.