A call to explore a broader use of human
papillomavirus vaccines and the validation of a simple
oral screening test for HPV-caused oral cancers are
reported in two studies by an investigator at the
Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins.
Leading HPV expert Maura Gillison, the first to
identify HPV infection as the cause of certain
oral cancers and who identified multiple sex partners as
the most important risk factor for these
cancers, reports her latest work Nov. 3 in the journal
Clinical Cancer Research and in a Centers for
Disease Control and Prevention monograph. The CDC report on
HPV-associated cancers appears online
Nov. 3 and in the Nov. 15 supplement edition of
Cancer.
In the CDC report, believed to be the first and most
comprehensive assessment of HPV-associated cancer data in
the United States, investigators analyzed cancer registry
data from 1998 to
2003 and found 25,000 cancer cases each year occurred at
cancer sites associated with HPV
infection. In additional analysis, Gillison and colleagues
at the National Cancer Institute identified HPV
infection as the underlying cause of approximately 20,000
of these cancers.
Gillison and her team found that approximately 20,000
cases of cancer in the United States
each year are caused by HPV infection. Oral cancers are the
second most common type of HPV-
associated cancers and are increasing in incidence in the
United States, particularly among men. Add
to that anal, penile, vaginal and vulvar cancers that are
also linked to HPV infection, and Gillison says
that these cancers, when combined, equal the number of
cervical cancers, the most common and well
known of the cancers caused by HPV.
While about one-quarter of HPV-linked cancers occur in
men, vaccines are currently approved
for use only in girls and young women for cervical cancer
prevention. "We need to have a more
comprehensive discussion of the potential impact the HPV
vaccine could have on cancer rates among
men and women in this country," said Gillison, an associate
professor of oncology at Johns Hopkins.
"Currently available HPV vaccines have the potential to
reduce the rates of HPV-associated cancers,
like oral and anal cancers, that are currently on the rise
and for which there are no effective or
widely applied screening programs." Gillison said, however,
that studies are needed to confirm that the
vaccine effectively prevents HPV infections that lead to
oral and anal cancers.
Gillison's findings were part of a project known as
ABHACUS, for Assessing the Burden of HPV-
Associated Cancers in the United States. The data studied
came from the CDC's National Program of
Cancer Registries and the National Cancer Institute's
Surveillance, Epidemiology and End Results
program. More than 80 investigators from across the country
participated in the project, which
addressed a variety of HPV cancerŠassociated issues,
including racial disparity, economic impact,
behavioral risk factors and cancer mortality.
Other than prevention, early detection is held by
cancer experts as the best way to control
cancer. In the Clinical Cancer Research study, the first to
track the disease and related oral
infections over an extended period, Gillison found that
simple "swish and spit" oral rinses can
successfully track oral HPV infection over time. These
findings open the door to a potential
noninvasive screening test to detect the disease and
monitor for tumor recurrence. Head and neck
cancer is the broad term for a variety of cancers of the
oral cavity, including the tonsils, base of the
tongue and the side and back walls of the throat.
The study found that oral rinses successfully detected
high-risk HPV infections in patients with
HPV 16Špositive head and neck cancers for up to five years
after treatment for their cancer. Gillison
said that the findings indicate a high rate of persistent
infection and reaffirm the connection
between high-risk types of HPV and HPV-positive head and
neck cancers.
In the study, the researchers used oral rinses to
collect cells shed from inside the mouths of
135 head and neck cancer patients. The researchers
genetically sequenced the DNA obtained from
the rinses and tumor samples to identify those with
HPV-positive cancers and determine the HPV
type. There are approximately 120 types of HPV, but HPV 16
is one of the two most common
associated with cancer.
The analysis revealed 44 patients with HPV 16-positive
tumors and found that these patients
were more likely to have continuing oral HPV 16 infections
both before and after cancer treatment.
While this study did not link the continued post-treatment
infections to tumor recurrence, it was
noted that patients with high-risk oral HPV infections
prior to therapy maintained high rates of
infection after completing therapy. The team plans further
long-term research to determine if this
continued infection leads to cancer recurrence.
In 2000, Gillison identified HPV-positive head and
neck cancer as a distinct subtype of the
disease and linked it to improved survival.
"There is no question of cause," Gillison said. "It
has now become a question of tracking the
infection over time to identify those at risk of developing
cancer or cancer recurrence."
Other researchers participating in the study were Yuri
Agrawal, Wayne M. Koch, Weihong Xiao,
William H. Westra and Anna L. Trivett, all of Johns
Hopkins; and David E. Symer, of NCI.
The research was funded by the Oral Cancer Foundation,
the National Institute of Dental and
Craniofacial Research and the National Cancer Institute.