Increased test sophistication

March 1, 2009

Human papillomavirus
infection continues to slowly burn its way through populations around
the world, not discriminating by gender, race, or age. About 50% of
adults are reported to be infected, and more than 80% of females age 50
and older have had a detectable infection in their lifetimes. The
American Social Health Association reports that HPV is one of the most
common STDs in the United States. According to HPV Vaccine Statement
published by the Centers for Disease Control and Prevention (CDC),
Department of Health and Human Services, on Feb. 2, 2007, approximately
20 million Americans are currently infected, and another 6.2 million
people are newly infected each year.

The good news is that most genital HPV infections
are easily treated and clear up quickly (90% within two to three years),
and the vast majority of HPV infections are not categorized as high
risk. Despite these statistics, sexually transmitted HPV still causes a
major portion of cervical cancer by transforming normal cervical cells
into cancerous ones. The genotyping of HPV subtypes is a critical
component in the ongoing battle against this disease and offers
epidemiological researchers the insight needed for better prevention
strategies including vaccine programs and efficient HPV screening.

Though HPV vaccine is a preventive measure, it still cannot
prevent all types of HPV infections.

Complicating the HPV scenario is the fact that
most people with HPV infections do not develop any noticeable symptoms
or health problems. That is why screening patients for HPV subtypes can
be the single most important step toward slowing the spread of HPV.
Today, HPV screening is the only sure-fire way to detect HPV infections
during the development of HPV-induced cervical cancer that, otherwise,
would lie hidden.

HPV was first discovered in 1949; and, so far,
more than 100 HPV subtypes have been identified and further classified
as high risk and low risk, depending on whether they put a person at
risk for cancer. Counted among the high-risk group and the most common
in cervical-cancer patients are HPV 16 and 18 (which, together, are
associated with more than half of cervical-cancer cases in the United
States and Europe), as well as HPV 31 and 45 (detected in 5% to 10% of
patients, respectively). Currently, two HPV vaccines are on the market.
One (HPV4) targets HPV 16 and 18, along with 6 and 11 (which, together,
cause about 90% of genital warts). The other vaccine targets HPV 16 and
18. Clinical trials show that these vaccines do offer some
cross-reactive protection against virus strains 31 and 45.

Although cervical-cancer screening has improved
significantly since the Food and Drug Administration's (FDA) approval of
HPV DNA detections assays — the Hybrid Capture 2 assay (HC2) and the
SPF10 assay, for the detection of carcinogenic HPV — with cytology for
primary screening, carcinogenic HPV testing has one critical limitation:
poor positive predictive value. Put simply, carcinogenic HPV tests can
only screen for either high-risk or low-risk HPV groups;. it cannot
identify individual HPV subtype. Given the facts that 1) risk for
cervical pre-cancer and cancer varies among carcinogenic HPV genotypes
and 2) genotype-specific persistence is strongly linked to presence or
development of cervical cancers, HPV genotyping tests must be able to
differentiate the higher-risk from the lower-risk strains for effective
monitoring of HPV infection.

In addition, HPV vaccination cannot prevent HPV
infection outside of the vaccine-targeted HPV types. Testing negative
for only the vaccine-targeted types does not rule out past exposure and
persistent monitoring could improve the PPV of HPV screening. HPV
vaccine is proving that it can prevent HPV infections that cause most
cases of cervical cancer in women as well as other less-common genital
cancers (i.e., cancers of the anus, vagina, and vulva). Though HPV
vaccine is a preventive measure, it still cannot prevent all types of
HPV infections.

The United States and European countries
routinely recommend that girls between ages 9 and 12 get vaccinated.
“Catch-up” vaccination is recommended for females between ages 13 and 26
who either have not been vaccinated or completed the vaccine series.
Some countries (e.g., Australia and New Zealand) recommend vaccination
up to age 45. This is solidly grounded policy. According to a study
presented at 24th International Papillomavirus Conference in November
2007 in Beijing, the vaccine targeting the HPV4 types indicated 81%
efficacy against pre-cancerous lesions among 3,800 women ages 24 to 45.
As the trend to expand the recommended age for HPV vaccine continues,
the ability to identify the type of HPV infection is essential prior to
vaccination in order to maximize the effectiveness of HPV vaccine.

To help screen patients for various infection
subtypes, new screening technologies are coming to the fore. One such
method includes vaccine-targeted HPV genotyping product, a “one-time
PCR” that can detect HPV types 16, 18, 11, 6, 31, and 45, all of which
can then be easily prevented with the HPV vaccine. The other test is
designed to genotype HPV 16 and 18, and to screen for 14 high-risk and
five low-risk HPVsubtypes at the same time. Also there is a product
capable of simultaneously detecting 21 types of HPV (16 high-risk and
five low-risk) subtypes. Yet other innovative approaches detect the most
common STD-causing pathogens, Chlamydia trachomatis and
Neisseria gonorrhoeae
, along with HPV infection.

Jong-Kee Kim, PhD, is the CTO of
Seegene Institute of Life Sciences in Rockville, MD, and Seoul, South