Comprehensive Gynecology 12th Ed

Chapter 28: Intraepithelial Neoplasia of the Lower

Genital Tract (Cervix, Vulva):
Etiology, Screening, Diagnostic Techniques, Management
Carcinoma of the Cervix
One of the most common malignancies in women
Second or third most common cause of cancer death
in women worldwide
Screening test, the Pap smear, reduce the incidence
of the disease by at least 70%.
HISTORY, EPIDEMIOLOGY, AND INFECTION
In the early part of the 20th century, epidemiologic studies
demonstrated that the cancer was closely linked to sexual
activity.
Early age at first intercourse and multiple sexual partners
were the most consistent risk factors
Suggested that there might be an infectious agent passed
through sexual activity that causes cervical carcinoma.
Human Papillomavirus (HPV) Infection that the true
cause of cervical cancer was discovered.
In 2008, Professor Harald zur Hausen received the Nobel
Prize in Medicine for his discovery that HPV was the
causative organism.
Papillomaviruses
found in almost all mammalian species
generally species-specific
double-stranded DNA viruses that replicate within epithelial
cells
group that infects humans includes more than 120 types.
Within these types, there is further
grouping, so that the types that commonly are found on
one
anatomic part of the body are not the same as found on
other
parts. For example, plantar warts on the feet are not
caused by
the same HPV types as warts on the hands. In several
locations,
infection with HPV is associated with a clinically evident
lesion,
the wart. Unfortunately, this has led to HPV being labeled
as the
wart virus despite the fact that many infections, indeed
most in
the genital tract, do not form warts.
Approximately 40 types of HPV are known to infect the
genital
tracts of men and women. Of these, at least 13 are
associated
with cancer. The other types are associated with genital
warts or
are unimportant infections with no clinical symptoms.
Because

it is not possible to grow the virus in the laboratory, it has

taken
many years and much indirect evidence to determine that
an
infection with one of the cancer-associated types is a
necessary
precursor to squamous cell carcinoma and most cases of
adenocarcinoma
of the uterine cervix. However, the virus is an incomplete
cause because the vast majority of genital HPV infections
do not result in cancer.
Epidemiologic evidence is conclusive that the virus can be
passed from one individual to another through sexual
activity.
However, HPV DNA can be found on clothing and other
surfaces
and, thus, fomite transmission might be possible. However,
according to Winer and colleagues, it is unlikely. It will not
be
possible to determine whether such material is infective
until a
method of culturing HPV is developed.
Studies of college students and other groups performed by
Wheeler and colleagues in 1996, and Moscicki and
associates
in 1998, 2004, and 2008 have confirmed that most men
and
women acquire a genital HPV infection within a few years
of
the onset of sexual activity. The most common type
identified
in the general U.S. population is type 16, which is also the
type
most highly associated with cancer. Studies by Ho and
associates
in 1998 tested participants for evidence of the virus at
regular
intervals several months apart; most of the detected
infections
cleared within a few months, although some persisted for
as long
as 36 months. Recently, it has been found that many
infections
last only a few weeks, suggesting that the previous studies
underestimated
the cumulative incidence of the disease. Many
investigators
now believe that in sexually active individuals, infection
with HPV at some time is almost universal.
Despite almost uniform infection with HPV, the vast
majority
of women do not develop cervical cancer. That is, of the
millions
and millions of women who are infected with HPV, only a
few will ever develop cervical cancer, even if they are never

screened and/or treated for preinvasive lesions.

Longitudinal
studies have now confirmed this (Fig. 28-1). The search for
a
predictive measure that will distinguish between those
women

who are infected and will clear the disease and those in
whom
the infection will persist and lead eventually to carcinoma
has
653