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U N I T 1 1
Genitourinary and Reproductive Function
pregnancy and prolonged oral contraceptive use cause
the squamocolumnar junction to “roll out” or evert from
its original position inside the external os to a position
of enlarged cervical surface. Exposure of the columnar
cells to low pH vaginal secretions, irritants, and a chang-
ing hormonal environment lead to a gradual transforma-
tion from columnar to squamous epithelium—a process
called
metaplasia
(see Chapter 2). The area of dynamic
change where metaplasia takes place is called the
trans-
formation zone
.
6,7
The transformation zone is a critical
area for the development of cervical cancer.
Cervicitis
Cervicitis is an acute or chronic inflammation of the
cervix. Acute cervicitis may result from the direct infec-
tion of the cervix or it may occur secondary to a vaginal
or uterine infection. It may be caused by a variety of
infective agents, particularly endogenous vaginal aer-
obes and anaerobes,
Streptococcus
,
Staphlococcus
, and
Enterococcus
.
7
Other specific organisms include
C. albi-
cans
and herpes simplex virus. Some agents are sexually
transmitted, whereas others may be introduced by for-
eign objects such as tampons or pessaries.
7
With acute cervicitis, the cervix becomes reddened
and edematous. Irritation from the infection results
in copious mucopurulent drainage. Depending on the
causative agent, acute cervicitis is treated with appropri-
ate antibiotic therapy.
7
Chronic cervicitis represents a low-grade inflamma
tory process. It is seen most commonly in parous women
and may be sequelae to minute lacerations that occur
during childbirth, instrumentation, or other trauma.
The organisms usually are nonspecific—often staphylo-
coccal, streptococcal, or coliform bacilli. The symptoms
of chronic cervicitis are well defined. The cervix may
be ulcerated or normal in appearance; it may contain
nabothian cysts; the cervical os may be distorted by old
lacerations or everted to expose areas of columnar epi-
thelium; and a mucopurulent drainage may be present.
Untreated cervicitis may extend to include the devel-
opment of pelvic cellulitis, low back pain, dyspareunia,
cervical stenosis, dysmenorrhea, and ascending infection
of the uterus or fallopian tubes. Diagnosis of chronic
cervicitis is based on vaginal examination, colposcopy,
Pap smear cytology, and occasionally biopsy to exclude
malignant changes. Treatment usually involves cryosur-
gery or cauterization, which causes the tissues to slough
and leads to eradication of the infection.
Premalignant Lesions and Cancer
of the Cervix
Cervical cancer is one of the best-understood cancers
and potentially one of the most preventable. In the
1950s cervical cancer was the leading cause of cancer
deaths in women in the United States, but the death rate
has declined steadily over the past several decades due
to prevention and early detection by cancer screening.
6
Worldwide, however, cervical cancer remains the second
most common cancer in women.
7
Pathogenesis and Risk Factors.
The pathogenesis
of cervical cancer has been linked to HPV infection
by a series of epidemiologic, pathologic, and molecu-
lar genetic studies. Of the approximate 100 types of
HPV, about 40 affect the anogenital tract. About 15 of
these types are associated with cancer and are known
as high-risk groups, with subtypes 16 and 18 being the
most important in terms of cervical cancer pathology
(see Chapter 41).
6
HPV 16 accounts for almost 60% of
cervical cancer cases, and HPV 18 for another 10%.
7
By contrast, low-risk types 6 and 11 are associated with
genital warts (condylomata acuminata).
Most cervical cancers begin their development in the
squamous columnar cells of the transformation zone.
The metaplastic cells within this zone represent the
newest and least mature cells in the cervix. HPV infects
immature basal cells of the squamous epithelium, but
not mature superficial cells that cover the exocervix,
vagina, or vulva, explaining the vulnerability of cells
in the transformation zone to malignant transforma-
tion. Even though HPV has been firmly established as a
causative factor in cervical cancer, the evidence does not
implicate HPV as the only risk factor. Most HPV infec-
tions are transient, indicating the host’s defense system
is able to eradicate the virus before it can cause neo-
plastic changes in cervical cells. Other factors such as
cigarette smoking, dietary and nutritional factors, early
age of first sexual intercourse, family history of cervical
cancer, immunodeficiency (e.g., HIV infection), multi-
parity, and hormonal and other factors may play a role
in determining whether a woman with HPV infection
develops cervical cancer.
6,18
Two types of HPV vaccines are currently avail-
able to prevent HPV infection: a quadrivalent vaccine
(Gardasil) to prevent infection by HPV subtypes 16, 18,
6, and 11,
19
and a bivalent vaccine (Cervarix) to prevent
infection by subtypes 16 and 18.
20
The quadrivalent vac-
cine has been approved for females and males between
the ages of 9 and 26 years, optimally before initiation
of sexual activity. Human papillomavirus subtypes 6 and
11 cause the majority of venereal warts, while types
16 and 18 are responsible for over 80% of all cervical
cancers. Because the bivalent vaccine does not protect
again HPV subtypes 6 and 11, which are responsible for
the majority of condyloma acuminiata (genital warts),
it is approved for females between the ages of 9 and
26 years, but not for males.
Premalignant and Malignant Lesions.
One of the
most important advances in the early diagnosis and
treatment of cancer of the cervix was made possible
by the observation that this cancer arises from pre-
cancerous lesions that begin with the development of
atypical cervical cells. There are variations in cell size
and shape and changes in the nuclear and cytoplasmic
parts of the cell, commonly referred to as
dysplasia
(see Chapter 7). These precancerous changes represent
a continuum of morphologic changes with indistinct
boundaries that may gradually progress to cancer in
situ and then to invasive cancer, or they may spontane-
ously regress.
