By Shira Klapper, Senior Writer/Editor

A “From the Archives” Exclusive— “From the Archives” series features articles from past issues of the Journal of Clinical Oncology (JCO), selected by the Editor-in-Chief based on their important contribution to oncology research.

In the 1980s, oncologists and researchers took note of an interesting trend in head and neck cancer. While cancers such as laryngeal and oral cavity were declining, another cancer—oropharyngeal squamous cell carcinoma (OPSCC)—saw its numbers increasing. The decrease in the non-OPSCC cancers could be easily explained—those subsets of head and neck cancer were caused by tobacco and alcohol use, and tobacco use had experienced a steep decline since the Surgeon General’s 1964 landmark report linking tobacco use to cancer. To explain the rise in OPSCC, researchers turned to another historic trend—the increase, since the late 1970s, in the number of people carrying human papillomavirus (HPV), an infection known to cause OPSCC.

While the theory linking the rise of HPV to increased rates of OPSCC was widely accepted, it was not until 2006 and 2011 that two different studies directly analyzed the OPSCC tumors to see whether they showed increased rates of HPV infection over time—a trend that, if positive, would show definitive evidence for the causal connection between the infection and the virus. The 2011 study was published in JCO and was the first American study to show that, indeed, from the 1980s through the 2000s, the proportion of tumors that carried HPV rose over time and that the rise tightly paralleled the increase in rates of OPSCC. This observation led to the study’s conclusion: the increase in cases of oropharyngeal cancers in the United States since 1984 is caused by HPV infections.

Anil K. Chaturvedi, PhD

The first American study to directly link HPV and OPSCC

That 2011 study, “Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States,” published in the Journal of Clinical Oncology, online, October 3, 2011, provided concrete numbers for the theory connecting OPSCC and HPV.

“We were able to show that the proportion of tumors that were positive for HPV infection increased significantly over time,” said the study’s lead author, Anil K. Chaturvedi, PhD, a researcher at the National Cancer Institute. “We were able to see that in the late 1980s, about 16% of OPSCC tumors were positive for HPV infection and that in the early 2000s that number rose to about 72%. These numbers show that the prevalence of HPV tumors has significantly increased over time.”

DNA assays showed increased rates of HPV-positive tumors

To carry out the study, the researchers gathered 271 tumors gathered from the three registries—in Hawaii, Illinois, and Los Angeles—that participate in the Surveillance, Epidemiology, and End Results (SEER) Program’s Residual Tissue Repository Program. The tumors, which dated from 1984 to 2004, were then analyzed using DNA assays and divided into two groups: HPV-positive or HPV-negative.

“Basically, what we were able to do was ask the question: how many tumors were HPV-positive in the 1980s, how many of them were positive in the early-1990s, late-1990s, and early 2000s?” said Dr. Chaturvedi. “And then we were able to separately investigate incidence trends over time for the positive and negative counterparts and were able to show that for HPV–negative tumors, the incidence actually declined by 50% during that three-decade period and that HPV-positive tumors actually increased substantially over the same time period.”

Prediction: more OPSCC in the future, with men bearing the burden

The JCO study also made predictions about the future rates of OPSCC in the United States. Using current data from nine SEER registries, the study projected that by 2020, 8,700 people annually will be diagnosed with HPV-positive OPSCC, surpassing the number of people expected to be diagnosed with cervical cancer in that same year. In addition, the study predicted that by 2030, OPSCC will become the most common head and neck cancer.

The rising numbers of OSPCC diagnoses will markedly change the demographics of head and neck cancer patients. For one, OPSCC is skewed heavily towards male patients, a gender imbalance that is relatively higher than that observed for other head and neck cancers. Also, compared to patients whose cancer was brought about by alcohol and tobacco use, patients with OSPCC are younger.

In addition, this study and previous studies have found that patients with HPV-positive OSPCC differ from patients with head and neck cancer in an important way: they live longer. According to Dr. Chaturvedi, this difference in survival has important clinical implications.

“It raises the question that is being addressed in several ongoing studies, which is, do we treat this patient population the same way we have treated OPSCC in the past, or do we come up with targeted therapies for these patients in view of their improved survival and lower age?,” said Dr. Chaturvedi.

And faced with a growing number of patients diagnosed with OPSCC worldwide, the oncology community can expect that questions such as these will only become more important in the years to come.

Anil K. Chaturvedi, PhD, is an investigator at National Cancer Institute in the Division of Cancer Epidemiology and Genetics.

Source

Click here to read the abstract.

Click here to read the PDF.

Chaturvedi, AK, Engels, EA, Pfeiffer, RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the united states. J Clin Oncol. 2011. Published online 10.3.2011.

The Exclusive Coverage series on ASCO.org highlights selected research from JCO with additional perspective provided by the lead or corresponding author.

@ 2014 American Society of Clinical Oncology