HPV: Prevention of Cervical Cancer Through Vaccination

   has been hailed by gynecologists
as the most significant breakthrough
in Women’s Health of the century. The first
HPV Vaccine has been approved by the
FDA. HPV is a DNA virus that infects skin
and mucosal tissues and causes cell changes
that lead to what is known as cell proliferation
(overgrowth) and conversion to neoplastic
changes (premalignant and malignant).
These vaccines have the ability to prevent
the majority of cervical cancers, a cancer
thought to be virtually 100% preventable.
Two vaccines are: one, the newlyapproved
Merck quadrivalent vaccine Gardasil
®, targets four types of the HPV virus:
16, 18, 6, 11. It is a vaccine that gives the
individual a fairly rapid immunity to one of
four types of the HPV virus. Merck has targeted
the HPV 16 and HPV 18 viruses
because they together are the responsible for
70+% of cervical cancer cases. They included
6, 11 because they cause genital warts
and abnormal pap smears, and the vaccine
has the ability to prevent 90% of those.
There are over 100 identified types of the
HPV virus. Asecond vaccine was developed
to target only HPV 16 and 18, called Cervarix
®. FDA approval is still being sought.
The quadrivalent vaccine that has been
approved is a series of three shots, with the
second shot administered two months after
the first, followed by a final shot four
months later. The injection is not that of a
live virus, but that of the proteins of the
outer shell that are called VLPs or virus
like particles, that are perceived as the virus
by the body, and robust antibodies are
formed to that particle. With this antibody
formation, for at least the few years that the
vaccine has been studied, there is virtually
complete immunity formed against HPV.
The immunity means that persistent infections
are absent. There is almost complete
protection against the virus acquisition in
those not infected, even in those that didn’t
adhere completely to the study protocol.
Cervical cancer has been a world wide
epidemic for generations. Over 500,000
cases are diagnosed world-wide; over
250,000 women die. They die in the midst
of America too, but the numbers pale, and
fewer than 4,000 American women die each
year here of this disease. This is due to the
wide availability of pap smears, accurate
tests to diagnose the primary causative
agent, referral to gynecological treatment
and effective elimination of most pre-invasive
cervical disease. We in the United
States also do fairly well at preventing the
diseases of anal cancer, vaginal cancer, vulvar
cancers, the rare penile cancer and
laryngeal papillomous growths as well. Yet,
even with our medical system of track and
triage the burden of genital warts has continued
to grow: 20 million infected Americans,
and most unknowingly. Since only
4,000 die and 20M are infected, its not cancer
that is the real American Tragedy of the
disease here. It is the ever increasing numbers
of young women who have contracted
the virus and have to deal with the consequences:
financial, emotional, physical and
mental. Take the medical scenario of the
only treatments of pre-invasive disease
being surgical excision. There are legions of
young women who have had large areas of
the cervix permanently removed in
an attempt to ward off the
cancer. Genital warts are
treated in much the
same way, removing
the affected tissue.
Since elimination
of the wart is not
always accompanied
by elimination
of the
viral infection
causing the wart,
recurrences are
common and resistance
to treatment
common as well. Other
consequences of infection
are depression, lower sex drive,
lower self esteem, anxiety, and the issues of
“pre-existing” i.e. “not-covered” conditions
on your next insurance policy, which causes
economic burdens for those in treatment.
A focus group of girls and women with
the HPV disease might have a 17 year-old
who’s had abnormal pap smears for many
years, has had two procedures to remove the
dysplastic tissue, and is at risk for consequences
such as cervical incompetence in
pregnancy resulting in miscarriage; a 40
year-old with multiple excisional procedures
of the vulva to remove abnormal tissue
who is at risk for sexual dysfunction; a
52 year-old with cervical cancer; a 26 yearold
with multiple genital warts, who will
likely require at least 3-4 visits just to
remove this round of the infection, and a 28
year-old pregnant woman with an abnormal
pap smear. In addition to the numbers of
young women with the infection, we now
estimate 80+% of us will acquire the HPV
infection by age 50, and 20% of women
who have contracted the disease have had
only one partner. This group will ask where
they got the infection: unable to say, as tests
for HPV are so newly available we can’t say
how long an individual has harbored her
infection; how likely they will resolve the
infection. About 70% will clear sometime
after 6 months, closer to 90% of infections
clear by 2 years, and by 5 years if it’s going
to clear at all. Questions remain: when is
sex safe again and what should I tell my
partner? Disclosure issues are troublesome
since there’s no real test for the men.
Who will need the vaccine? We know
that about 50% of adolescent women will
contract HPV within three years of becoming
sexually active, so the vaccine is most
likely to help those women prior to their
debut into sexuality. Administering an STD
vaccine to a child, in a sheltered life, with
monogamous parents who married when
they were virgins, is looking to be a very
hard sell politically. No one has
an emotional problem preventing
small pox, or
mumps, or whooping
cough, or polio, but
when it comes to
the S word topic,
apparently that is
a NIMBY discussion.
Abstinence
has been
called 100%
effective 100% of
the time, and for
the straight genitalto-
genital contact disease
that is probably
true, but for variations in
sexuality, not so good. So young
people of both sexes probably need vaccinations.
The Merck vaccine has been tested
in girls and women from 9-26.
Condoms don’t work effectively to protect
against HPV disease. They aren’t used
consistently, aren’t used with appropriate
microbicial concentrations of spermicide,
and plain and simply do not cover the potential
odd wart or two that sits on the male
body instead of the shaft, or the rectum, or
the skin of the scrotum, or the rectal areas, or
the female perineal areas. Latex condoms do
help to block transmission, but if any skinto-
skin contact occurs in an affected area
transmission will occur. Suffice it to say,
even a body bag wouldn’t do it, because
slippage, breakage, and plain old holes let
alone the lax application of said bag would
not work, does not work. Now those of us in
the business do need to add they do drastically
reduce the rates of other infections:
gonorrhea, Chlamydia (a cofactor in the cervical
cancer cases), herpes (another cofactor
of cervical cancer) and the rates of HIV
infection, and by the way, are very effective
at preventing unwanted pregnancy. Yet in
the midst of an STD epidemic the Congress
has been set on legislation designed to highlight
condom’s failures rather than on strategies
that would increase their use.
Vaccines, if effective, are the only way
to go when preventing a case of a sexually
transmitted disease, or an outbreak, or an
epidemic, or a pandemic. Years ago our
CDC decided that it’s only logical, that if
gonorrhea is spread through sex, and you
find an individual with said case, treat the
partner who gave it to him or her and you’ll
stop the chain of events. With rules, regulations,
laws, troops of more-or-lessinformed
public health workers, and a
patchwork of policies and procedures,
where has it gotten us? We see pretty stable
rates of most of the common sexually transmitted
diseases within the US. In the year
2000 we had over 19 million new infections
reported. We have done a good job of
decreasing syphilis by the way, but still
HPV itself is responsible for about 50% of
new STDs. And we forge ahead with these
policies, as it still ‘seems prudent’, but
there’s not a single well done prospective
study to say this is effective.
The HPV vaccines have the ability to
prevent disease, save money, and save
lives. This is not debatable. Many of the
available vaccines we do take are for diseases
that are frankly rare; this one is not.
What is debatable is how to overcome the
significant political and social obstacles to
accepting the vaccine. Is getting vaccinated
a ticket to loose or so-called unsafe sexual
behavior? Moral extremists have been
heard to say that STDs are just payment for
out-of-wedlock sexuality. Both sexes will
need to be vaccinated, but will public distrust
of vaccine safety allow boys to be vaccinated
to prevent diseases in women? Will
vaccinated women stop getting pap smears
when we know this will not prevent every
HPV infection or every cervical cancer?
Will the vaccine reduce condom use and
inadvertently increase unwanted pregnancies?
We’ll need to be administering more
of those morning after pills if condoms
decline and that will be another topic for
future discussion.
It is unlikely that legislation is going to
rubberstamp HPV vaccination policies or
protocols. It is most likely that the vaccine’s
acceptance will rest largely with
individual providers, patient education and
discussion and maximal understanding of
the disease’s serious consequences, the
consequences of avoidance of vaccination.
Dr. Trupin is a paid research consultant
for Merck & Co., Inc. and other women’s
health companies.