Screen All New Cancer Patients for Hepatitis?

Kristin Jenkins

January 23, 2019

A new study has found "a large reservoir of patients with cancer and undiagnosed hepatitis virus infections" and has reignited the question of whether all newly diagnosed cancer patients should be screened for hepatitis.

The Viral Screening in Newly Diagnosed Cancer Patients (S1204) study involved 3051 patients and found that 6.5% had previously been infected with hepatitis B virus (HBV), 0.6% had chronic HBV infection, 2.4% had hepatitis C (HCV) infection, and 1.1% were infected with HIV.

The study was published online on January 17 in JAMA Oncology.

At enrollment, 87.3% of patients did not know that they had previously been infected with HBV. Similarly, 42.1% of the cases of chronic HBV infection, 31.0% of the cases of HCV infection, and 5.9% of the cases of HIV infection were undiagnosed.

Cancer patients with HBV or HCV infection are at risk for viral reactivation and potentially life-threatening clinical outcomes, say the authors, led by Scott D. Ramsay, MD, PhD, director of the Hutchinson Institute for Cancer Outcomes Research at the Fred Hutchinson Cancer Research Center, in Seattle, Washington.

"Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient," they add.

Universal screening for HBV and HCV prior to cancer therapy "may be warranted," they write.

The investigators conclude, however, that "[t]he low rate of undiagnosed HIV infection may not support universal screening of newly diagnosed cancer patients [for HIV]."

Screening Could Prevent Complications

Universal screening for HBV, HCV, and HIV infection is not routinely performed in patients diagnosed with cancer. What's more, the use of such screening remains controversial among oncologists, the researchers point out.

These results "provide new evidence to inform a discussion in the oncology community about whether we should require hepatitis screenings," said Ramsay in a statement.

Universal screening could prevent complications from hepatitis, such as liver failure and kidney disease, the investigators say. Immunosuppressive cancer drugs such as rituximab (Rituxan, Genentech, Biogen Idec) — used to treat CD20-positive T-cell lymphomas and leukemias — can cause some viruses to reactivate and multiply.

"Because the true risk of severe adverse events associated with most cancer treatments in persons with latent infections is unknown, the putative benefits of delaying or modifying cancer treatment remain speculative...," the authors say.

However, they add, "...the risk that these changes pose to outcomes for patients with newly diagnosed cancer are real."

Study Details

For the study, data were collected from patients enrolled at nine academic and nine community oncology centers affiliated with the SWOG (formerly the Southwest Oncology Group) Cancer Research Network, a National Cancer Institute–sponsored cancer clinical trials cooperative group.

Data were collected between August 29, 2013, and February 15, 2017. The median age of the patients was 60.6 years, 60.4% of the patients were women, 18.1% were African Americans, and 18.3% were of Hispanic ethnicity.

Breast cancer was diagnosed in 34.7% of patients, blood/marrow malignancy in 12.1%, colorectal cancer in 11.9%, and lung cancer in 11.7%.

Of those patients who did not know that they had previously been infected with HBV, 27.4% had no known risk factors. Similarly, 21.1% of patients with chronic HBV, 32.4% of those with HCV, and 20.6% with undiagnosed HIV had no identifiable risk factors. This suggests that current risk-based models for screening may be insufficient, the researchers say.

Universal Screening for All New Cancer Patients

When approached for comment, Harrys A. Torres, MD, associate professor in the Department of Infectious Diseases at the MD Anderson Cancer Center, Houston, Texas, said this 18-center evaluation study was "extremely important."

Torres, who is also associate adjunct professor in the Department of Gastroenterology, Hepatology and Nutrition, is founding director of the HCV clinic — the first in the United States to manage HCV infection in all cancer patients.

"We agree with the authors that all cancer patients should be screened for HBV and HCV," said Torres.

All cancer patients should be screened for HBV and HCV. Dr Harrys Torres

"Now the push for universal screening is coming from a great many academic and community cancer centers, not just one," he told Medscape Medical News.

At MD Anderson, universal screening for HBV, HCV, and HIV has been standard practice in hematologic services since 2007. "This started after rituximab was found to be associated with hepatitis B reactivation," Torres said.

In 2016, screening for HCV infection at MD Anderson was expanded to include all patients with cancer, including those with solid tumors. The vast majority of cases are newly diagnosed, said Torres. The next step is to screen most patients for HBV and HIV as part of a stepwise plan.

Torres partially agreed with the study authors on the matter of universal HIV screening. However, he emphasized that more data are needed before it can be said that universal HIV screening is not warranted, particularly if screening is recommended for HBV and HCV.

Results from a 2014 MD Anderson study supported HIV testing in cancer patients before they started cancer therapy, he noted.

"These three infections can be acquired in the same way, have common risk factors, and can induce other cancers that can present as second primary cancers in patients coming with different underlying malignancies. I see this from an infection perspective, and transmission is going to be an issue. Now that we have the data for HBV and HCV, we have to get the data for HIV."

Torres pointed out that in the current analysis, Ramsay and colleagues found an increased risk for liver cancer as well as cancer of the prostate, lung, and breast.

In a 2018 study, Torres and colleagues reported that 15% of HCV-infected patients who had different primary cancers developed HCV-associated hepatocellular carcinoma as a second primary malignancy. This is an often overlooked presentation of liver cancer, they say.

The current study findings validate those from a 2018 MD Anderson study led by Jessica Hwang, MD, MPH, said Torres. That study demonstrated that universal HBV testing was more efficient than risk-based screening.

The results from the current study also parallel findings from 2017 study and a 2018 study, both of which showed that selective screening practices for HCV were not optimal for identifying all infected cancer patients, he said.

"With the availability of nucleos(t)ide analogues to treat HBV and direct-acting antivirals to treat HCV, infected cancer patients can be treated to prevent viral reactivation, progression of liver disease, and allow access to cancer treatment, including clinical trials," said Torres.

As previously reported by Medscape Medical News, there is evidence of the impact of reactivation of HBV and HCV infection in patients undergoing immunosuppressive chemotherapy. In two separate studies, researchers at MD Anderson concluded that greater surveillance for HBV and safer hematologic-sparing treatments for HCV are required.

In 2015, the American Gastroenterological Association issued a guideline for the prevention and treatment of HBV reactivation during immunosuppressive drug therapy.

Subsequently, a review and meta-analysis of prophylaxis management for HBV reactivation in patients with breast cancer undergoing chemotherapy was published, as reported by Medscape Medical News.

Until more data are available, the US Centers for Disease Control and Prevention and the US Preventive Services Task Force (USPSTF) recommend that universal one-time HIV screening be conducted in patients aged 13 to 65 years and in women who are pregnant, Torres pointed out.

One-time screening for HCV is also recommended for individuals born between 1945 and 1965, Ramsay and colleagues note.

"This is particularly relevant if we want to reduce transmission to uninfected persons and reduce the risk of AIDS-related events, such as development of AIDS-defining cancers," said Torres. The USPSTF is currently reviewing its screening guidelines and is expected to issue new recommendations, he pointed out.

The National Comprehensive Cancer Network recommends HIV screening for persons with newly diagnosed lymphomas, the researchers say. However, the American Society of Clinical Oncology and the National Comprehensive Cancer Network do not have recommendations for universal HCV and HIV screening.

In their article, Ramsay and colleagues acknowledge that universal screening would increase the cost of cancer care. Ramsay is currently conducting an analysis of results from another SWOG study to determine the cost-effectiveness of universal hepatitis and HIV screening. The results are expected later this year.

Torres said that three recently published articles that present cost analyses in the United States and Europe show that universal HCV screening in the community is cost-effective. Similar results are expected in cancer patients, given the significant morbidity and mortality of HCV in this patient population, he added.

The study was funded by the National Cancer Institute of the National Institutes of Health. Ramsey has disclosed no relevant financial relationships. A number of coauthors have disclosed relationships with industry. Torres has relationships with Gilead Sciences, Inc, and Merck & Company Inc, with all funds paid to the University of Texas MD Anderson Cancer Center. He also has financial relationships with Gilead Sciences, Inc, Merck & Company Inc, and Dynavax Technologies.

JAMA Oncol. Published online January 17, 2019. Full text

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