CERVICAL CANCER -
Information for Practitioners
The prognosis for patients with
cervical cancer is markedly affected by the extent
of disease at the time of diagnosis. Because a vast
majority (>90%) of these cases can and should be
detected early through the use of the Pap smear,[2]
the current death rate is far higher than it should
be and reflects that, even today, Pap smears are not
done on approximately 33% of eligible women.
Among the majorw factors that influence prognosis are
stage, volume and grade of tumor, histologic type,
lymphatic spread, and vascular invasion. In a large
surgicopathologic staging study of patients with clinical
stage IB disease reported by the Gynecologic Oncology
Group (GOG), the factors that predicted most prominently
for lymph node metastases and a decrease in disease-free
survival were capillary-lymphatic space involvement
by tumor, increasing tumor size, and increasing depth
of stromal invasion, with the latter being most important
and reproducible.[3,4] In a study of 1,028 patients
treated with radical surgery, survival rates correlated
more consistently with tumor volume (as determined
by precise volumetry of the tumor) than clinical or
histologic stage.[5]
A multivariate analysis of prognostic variables in
626 patients with locally advanced disease (primarily
stages II, III, and IV) studied by the GOG revealed
that periaortic and pelvic lymph node status, tumor
size, patient age, and performance status were significant
for progression-free interval and survival. The study
confirms the overriding importance of positive periaortic
nodes and suggests further evaluation of these nodes
in locally advanced cervical cancer. The status of
the pelvic nodes was important only if the periaortic
nodes were negative. This was also true for tumor size.
Bilateral disease and clinical stage were also significant
for survival.[6] In a large series of cervical cancer
patients treated by radiation therapy, the incidence
of distant metastases (most frequently to lung, abdominal
cavity, liver, and gastrointestinal tract) was shown
to increase as the stage of disease increased, from
3% in stage IA to 75% in stage IVA. A multivariate
analysis of factors influencing the incidence of distant
metastases showed stage, endometrial extension of tumor,
and pelvic tumor control to be significant indicators
of distant dissemination.[7]
Whether adenocarcinoma of the cervix carries a significantly
worse prognosis than squamous cell carcinoma of the
cervix remains controversial.[8] Reports conflict about
the effect of adenosquamous cell type on outcome.[9,10]
One report showed that approximately 25% of apparent
squamous tumors have demonstrable mucin production
and behave more aggressively than their pure squamous
counterparts, suggesting that any adenomatous differentiation
may confer a negative prognosis.[11] The decreased
survival is mainly the result of more advanced stage
and nodal involvement rather than cell type as an independent
variable. Women with human immunodeficiency virus have
more aggressive and advanced disease and a poorer prognosis.[12]
A study of patients with known invasive squamous carcinoma
of the cervix found that overexpression of the C-myc
oncogene was associated with a poorer prognosis.[13]
The number of cells in S phase may also have prognostic
significance in early cervical carcinoma.[14]
Human papillomavirus infection
and cervical cancer
Molecular techniques for the identification
of human papillomavirus (HPV) DNA are highly sensitive
and specific. More than 6 million women in the United
States are estimated to have HPV infection, and proper
interpretation of these data is important. Epidemiologic
studies convincingly demonstrate that the major risk
factor for development of preinvasive or invasive carcinoma
of the cervix is HPV infection, which far outweighs
other known risk factors such as high parity, increasing
number of sexual partners, young age at first intercourse,
low socioeconomic status, and positive smoking history.[15,16]
Some patients with HPV infection appear to be at minimal
increased risk for development of cervical preinvasive
and invasive malignancies, while others appear to be
at significant risk and are candidates for intensive
screening programs and/or early intervention.
HPV DNA tests are unlikely to separate patients with
low-grade squamous intraepithelial lesions into those
who do and those who do not need further evaluation.
A study of 642 women found that 83% had one or more
tumorigenic HPV types when cervical cytologic specimens
were assayed by a sensitive (hybrid capture) technique.[17]
The authors of the study and of an accompanying editorial
concluded that using HPV DNA testing in this setting
does not add sufficient information to justify its
cost.[17,18] Whether HPV DNA testing will prove useful
in patients with atypical squamous cells of undetermined
significance is being studied by the same group.[17]
Patients with an abnormal cytology of a high-risk type
(Bethesda classification) should be thoroughly evaluated
with colposcopy and biopsy.
Other studies show patients with low-risk cytology
and high-risk HPV infection with types 16, 18, and
31 are more likely to have cervical intraepithelial
neoplasia (CIN) or microinvasive histopathology on
biopsy.[16,19-21] One method has also shown that integration
of HPV types 16 and 18 into the genome, leading to
transcription of viral and cellular messages, may predict
patients who are at greater risk for high-grade dysplasia
and invasive cancer.[22] Studies suggest that acute
infection with HPV types 16 and 18 conferred an 11-
to 16.9-fold risk of rapid development of high-grade
CIN, [16,23] but there are conflicting data requiring
further evaluation before any recommendations may be
made. Patients with low-risk cytology and low-risk
HPV types have not been followed long enough to ascertain
their risk. At present, studies are ongoing to determine
how HPV typing can be used to help stratify women into
follow-up and treatment groups. HPV typing may prove
useful, particularly in patients with low-grade cytology
or cytology of unclear abnormality. At present, how
therapy and follow-up should be altered with low- versus
high-risk HPV type has not been established. For the
reference list please
click here
What do we know about diet
and cervical cancer?
The Expert Panel (WCRF/AICR)
concludes (Chapter 7.13, pages 301-304.To
download the 3 page chapter pdf click
here):
"There is limited evidence
suggesting that carrots protect against cervical cancer.
The evidence is too limited to conclude that any aspect
of food, nutrition, and physical activity directly
modifies the risk of this cancer."
Second Expert Report: Food,
Nutrition, Physical Activity, and the Prevention
of Cancer: a Global Perspective. World Cancer
Research Fund / American Institute for Cancer Research
(WCRF/AICR), Washington DC: AICR, 2007. 537 Pages.
Note: PDF file of the complete report is 12 MB in
size. More about this report can be found on the
“diet” link [or some other name later] of this website.
To download the entire report (pdf 12MB) please
click here.
To download a summary of the report (16 pages, pdf
1.2MB) please
click here
To download the report’s summary
in other languages than English (WCRF website), please
click here
MedlinePlus will direct you
to information to help answer health questions. MedlinePlus
brings together authoritative information from NLM,
the National Institutes of Health (NIH), and other
government agencies and health-related organizations.
MedlinePlus also has extensive information about
drugs, an illustrated medical encyclopedia, interactive
patient tutorials, and latest health news. Please
check the MedlinePlus online for cervical cancer
with an extensive, constantly updated resource list. Please
click here
RESOURCES
FOR PRACTITIONERS
The
resources listed here are organized so you find
the most useful material first. They are published
by well-known organizations working on cervical
cancer prevention and HPV vaccine access. All
PDF files listed can be downloaded from pacificcancer.org
Acknowledgment: This text is
adapted from the CDC website.
