HPV ANTIBODIES ARE DETECTABLE LONG BEFORE CANCER

About one third of the patients who went on to develop oropharyngeal cancer associated with human papillomavirus type 16 (HPV 16) had antibodies to the virus detectable in their blood years before clinical diagnosis of the tumor, a new study reports. The finding could lead to the development of a screening tool, the researchers suggest.

The study, conducted at the International Agency for Research on Cancer (IARC) and the National Cancer Institute (NCI), waspublished online June 17 in the Journal of Clinical Oncology.

The findings "are particularly important because of the worrying increase in this type of cancer," said Christopher Wild, PhD, director of the IACR. The dramatic increase in HPV 16-related oropharyngeal cancer in recent years is thought to be due to changing sexual practices, in particular an increase in oral sex.

"Our study shows not only that the antibodies are present prior to diagnosis — but that in many cases, the antibodies are there more than a decade before the cancer is clinically detectable," said lead investigator Aimée R. Kreimer, PhD, from the division of cancer epidemiology and genetics at the NCI.

"These results are very encouraging," added senior author Paul Brennan, PhD, head of the genetics section at the IACR.

"If the results are confirmed, future screening tools could be developed for early detection of this disease," he said in a statement. However, he cautioned that although they are "promising, these results should be considered preliminary."

Increase in This Type of Cancer

Oropharyngeal cancer includes cancers of the tonsils, the oropharynx, the soft palate, and the base of the tongue. In the past, it was a relatively uncommon cancer, traditionally associated with heavy tobacco smoking and heavy alcohol consumption, according to an IARC press release.

However, the incidence has increased dramatically over the past few decades in many parts of the world, especially Europe and North America. This increase is thought to be due to the growing number of HPV infections and to changing sexual practices, such as an increase in oral sex, the press release explains.

HPV 16 is now responsible for more than 50% of oropharyngeal cancer in some parts of the world — notably, Australia, Sweden, and the United States, Dr. Kreimer and colleagues report.

Blood Samples Taken Years Ago

For their study, the researchers investigated blood samples taken from people enrolled in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, a cohort of more than 500,000 adults in 10 European countries. These people, originally recruited in the 1990s, gave a blood sample at study enrolment, and have been followed since then.

From this cohort, the researchers identified 135 people who developed oropharyngeal cancer 1 to 13 years later.

They found that 47 of these people (35%) had antibodies against the HPV oncogene E6 in their blood up to 12 years before the onset of the disease.

"The true lead time may be longer," the researchers note. "It is unclear at what point HPV 16 E6 antibodies are generated and are detectable."

In a matched control group of 1599 people without oropharyngeal cancer, only 9 (0.6%) had HPV 16 E6 antibodies in their blood sample.

One of the 9 who tested positive for the HPV 16 E6 antibody subsequently developed anal cancer. This raises the question of whether the 0.6% HPV 16 E6 seropositivity rate in the control group indicates the assay's false-positive rate or that these people are at increased risk of eventually developing HPV-associated cancer, or a combination of the 2, the researchers write.

Specifically Oropharyngeal Cancer

The antibody findings result in a high adjusted odds ratio of 274 for the diagnosis of subsequent oropharyngeal cancer, the researchers report.

HPV 16 was not associated with risk for cancer in the oral cavity, the larynx, or the esophagus, they note.

"The fact that the tonsils are lymphoid organs and rich in antigen-presenting cells may contribute to the relatively long time between seroconversion and cancer diagnosis, making this finding specific to the oropharynx and theoretically unlike other HPV-associated cancer sites," they write.

The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online June 17, 2013. Abstract