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National Toxicology Program

National Toxicology Program

UPDATE NewsletterUPDATE NewsletterJanuary 2016

Five viruses are known human carcinogens, say NTP peer reviewers

By Robin Mackar
Reprinted from Environmental Factor

A panel of experts agreed with the National Toxicology Program (NTP) preliminary recommendations to list five viruses as known to be human carcinogens in the Report on Carcinogens (RoC). All five listings are based on sufficient evidence from human studies associating these viral infections with an increased risk of 1 to 10 different cancers, depending on the virus.

The panel at the December 17 meeting was charged with reviewing the five draft monographs and voting on whether the scientific evidence supported the NTP listing recommendation for each virus. Before the formal presentations for each virus began, Ruth Lunn, Dr.P.H., director of the Office of the RoC, gave an overview of the RoC process, which provides for scientific, public, and peer review input.

“There is great public health concern for this topic, since about 12 percent of cancers worldwide are linked to viruses, and there are no vaccines available for any of these five viruses,” Lunn said. She pointed out that the literature review for these viruses built on International Agency for Research on Cancer monographs on these topics.

For each virus, the panel concurred that there was significant exposure to persons residing in the United States. NTP will consider the panel’s comments and present updated monographs to the NTP Board of Scientific Counselors at its June meeting.

  • The viruses are discussed separately below.
  • Human T-cell lymphotropic virus type 1 — HTLV-1 is a retrovirus that people are exposed through biological tissues, for example, through blood transfusions, breastmilk, or sexual activity. It is most prevalent in Japan, the Caribbean, and the Middle East, with an estimated 15 million to 20 million people infected worldwide. NTP found there was sufficient human evidence for adult T-cell leukemia-lymphoma.
  • Epstein-Barr virus — EBV is a herpes virus, transmitted primarily through saliva. It is a common virus, infecting more than 90 percent of adults worldwide. The peer reviewers agreed with the NTP conclusions of sufficient human evidence for four types of lymphoma, nasopharyngeal cancer and stomach cancer, and limited evidence for another type of lymphoma.
  • Merkel-cell polyomavirus — Transmission for MCV is unknown, but the skin is the primary site for infection, which may be from environmental sources. Gloria Jahnke, D.V.M., health scientist for NTP, presented data from epidemiological, clinical, and molecular studies showing that MCV causes Merkel cell carcinoma. She also presented supporting mechanistic data.

    “This is a really well-written monograph and a very good overview of the research in this area,” commented Paul Lambert, Ph.D., from the University of Wisconsin School of Medicine and Public Health.

  • Kaposi sarcoma-associated herpesvirus  — KSHV is a herpes virus transmitted primarily through saliva. NTP contractor Stanley Atwood, with Integrated Laboratory Systems (ILS), discussed mechanisms likely to lead to cancer, including the strong role that immune suppression plays. He presented the cancer endpoints with sufficient evidence from human studies for Kaposi sarcoma and primary effusion lymphoma.

    Panelist Blossom Damania, Ph.D., from the University of North Carolina (UNC) School of Medicine, an expert on this virus, said there was also sufficient evidence for an HIV-associated disease, known as multicentric Castleman disease (plasmablastic variant). The panel unanimously agreed.

  • Human immunodeficiency virus type 1 — The panel agreed that HIV-1 is a known human carcinogen based on sufficient evidence from human studies. HIV is a retrovirus spread through sexual activity, infected drug needles, in utero from mother to child, and by infected breast milk.

Immunosuppression was discussed as the main mechanism for cancer, because HIV infection can weaken the body’s immune system, making it hard to fight off infections that may lead to cancer.

“There are over 3,900 cancers identified as occurring in HIV-infected persons, and NTP covered endpoints thought to contribute to greater than 90 percent of these cancers in this monograph,” said presenter Pamela Schwingl, Ph.D., an ILS contractor.

The panel agreed that there was sufficient human evidence for many cancer endpoints, including Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, anal and genital cancers, conjunctival cancer, and non-melanoma skin cancer. The panel felt there was limited evidence for liver cancer, oral cancers, and invasive cervical cancer.

(Robin Mackar is the news director in the NIEHS Office of Communications and Public Liaison and a frequent contributor to the Environmental Factor.)

Blossom Damania, Ph.D. Damania shared her knowledge about the molecular pathogenesis of KSHV and other viruses. (Photo courtesy of Steve McCaw)
Gloria Jahnke, D.V.M. Jahnke served as the program lead for the preparing the virus monographs. (Photo courtesy of Steve McCaw)
Rosemary Rochford, Ph.D. Rosemary Rochford, Ph.D., from the University of Colorado and an expert on EBV, provided helpful comments to NTP. (Photo courtesy of Steve McCaw)
Margarete Madeline, M.D. and Fred Hutchinson from the Cancer Research Center Margarete Madeline, M.D., left, from the Fred Hutchinson Cancer Research Center, and Lambert, conferred over epidemiological and mechanistic data. (Photo courtesy of Steve McCaw)
Charles Rabkin, M.D. Charles Rabkin, M.D., from the National Cancer Institute, voted on one of the actions put forward to the panel. (Photo courtesy of Steve McCaw)

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The Update Newsletter is produced by NTP Office of Policy, Review, and Outreach. The text is not copyrighted and can be reprinted without permission. If you use parts of the Update Newsletter in your publication, we ask that you provide us with a copy for our records. We welcome your comments and suggestions.

Director of Office of Policy, Review, and Outreach and Editor-in-Chief: Mary Wolfe | Managing Editor: Anna Lee Mosley