Overview
In 1979 the Canadian Task Force on the Periodic
Health Examination found that there was fair justification for the view
that the incidence and mortality of invasive cancer of the cervix could
be reduced by taking cervical smears (B recommendation). The optimum age
and frequency at which smears should be taken was not known but was identified
as a research priority. This basic position has not changed but in 199
1 the evidence was re-examined by the Task Force in response to the publication
of the Report of a National Workshop on Screening for Cancer of the Cervix.<
1>
Examining the ovaries at the time of cervical cancer screening should also be considered for women at high-risk of ovarian cancer (see Chapter 72).
Burden of Suffering
Cervical cancer is the eleventh most common cancer
among women in Canada. In 1993, an estimated 1,300 women developed cervical
cancer and about 400 died of the disease. In 1989, an estimated 10,000
potential years of life were lost due to cervical cancer. The major factors
known to be associated with the occurrence of cervical cancer are age of
first sexual intercourse, number of consorts, number of previous partners
of consorts, smoking, low socio-economic status and possibly infections
such as human papillomavirus. However, note that screening for human papilloma-virus
(Chapter 63) is not recommended as part of cervical cancer screening. Rather
the factors associated with the highest risk are having many sexual partners,
a consort with many sexual partners and an early age of first intercourse.
Most studies show that for each additional partner the risk appears to
increase linearly by a factor ranging from 0.5 to 1, up to a relative risk
of at least 9; for early age of first intercourse (before 17 or 18 years
of age), the relative risk has been reported to range between 2 and 3.
Depending upon the stage at which the disease is detected, five-year survival rates range from 90% for stage 1 to 10-15% for stage 4, suggesting that any screening measure which permits earlier detection will improve survival.
Maneuver
At present only one test is suitable for general
population screening, the Papanicolaou smear test. False positive test
results are not a major concern because a second smear can be taken and
colposcopy done with minimal risk and relatively little expense; however
some needless anxiety will be generated. False negative test results, on
the other hand, allow the disease to escape detection until it reaches
a less treatable stage. Even in well run laboratories estimates for false
negative error rates run as high as 25%. The error can result from failure
of the physician to obtain malignant cells from the cervix or failure of
the laboratory process, including misinterpretation of the slide. Obtaining
an adequate smear can be difficult since cytological abnormalities usually
arise at the squamo-columnar junction and the site of this junction regresses
up the cervical canal as a woman ages. As for laboratory error, the false
negative rate appears to be lower in laboratories that process a large
volume of smears.
Effectiveness of Screening
Although the etiology of cancer of the cervix
has been the subject of much debate and there are still uncertainties concerning
the progression of dysplasia and carcinoma in situ to invasive cancer,
there is evidence from both cohort and case-control studies that participation
in cervical cytology screening programs reduces the incidence of invasive
disease.<2-7> It has been estimated that somewhere between a quarter
and one half of carcinoma in situ progresses; for dysplasia, the proportion
is less. In the majority of cases progression appears to be slow. Models
of screening frequency indicate that even a ten year smear interval would
reduce the incidence of invasive cancer by about two-thirds. Because screening
for this disease is so widespread, a more precise measurement of its benefit,
as assessed by a randomized controlled trial, is not ethically possible.
Recommendations of Others
It is not our purpose to review the cohort and
case-control evidence since this material has been presented in three major
reports produced by the Canadian government during the last 15 years<2,8-9>
dealing exclusively with cervical screening policy. The first, known as
the Walton Report,<8> recommended that all women over the age of 18
who have had sexual intercourse should be screened and that, if the initial
smear showed no atypia, a second smear be taken in a year’s time to affirm
that the first was not a false negative. If both these and later smears
were normal, screening should be carried out every three years, until the
age of 35 and every five years thereafter to age 60.
In 1982 the Walton report was revised<9> because of concerns that the sexual freedom resulting from improvements in contraceptive technology might have induced an "epidemic" of cervical cancer among younger women. The recommendation for women under thiry-five was changed to annual screening. Since that time, however, it has been concluded that for the majority of cases the progression of dysplasia and carcinoma in situ is slow. As a consequence the third report, The National Workshop Report, published in 1991, returned to the original recommendation of screening every three years and, in the interests of simplicity, suggested continuation of this frequency for women over 35. Another change was extension of the surveillance period to the age of 69, since most invasive disease occurs in post-menopausal women, many of whom have never had a smear or have had one taken infrequently. The report also dropped the recommendation for more frequent screening for high-risk women. The Workshop urged the establishment of organized cervical screening programs with a central laboratory in each province, based on the assumption that programs with centralized laboratories would be in place throughout the country.
In 1989, the U.S. Preventive Services Task Force recommended regular papanicolaou testing for all women who are or have been sexually active. Beginning with the onset of sexual activity, the test should be repeated every one to three years at the physicians discretion up to age 65 after which testing may be discontinued if previous smears have been consistently normal. This recommendation is currently under review.<10>
Frequency of Routine Screening
Since no controlled trials have been carried
out, no well grounded scientific evidence exists on which to base recommendations
for the optimum frequency of screening. The recommendations of the most
recent National Workshop<1> are largely based on the report from the
International Agency for Research on Cancer<11> which, in turn, was
based on case-control studies and computer models constructed with parameters
derived from cohort studies. However, Knox<12> has recently published
an analysis showing that estimates of the relative protection of screening
(and therapy) derived from such case-control and cohort studies are potentially
invalid. The estimate depends on the true protective effect of the test
and therapeutic procedures but is also determined by the ratio of the "uptake
rate" of the screening procedure (or proportion being screened) in the
case population and control population. If the uptake is unequal in the
two groups, then the estimate may be biased. The greater the uptake of
screening in the control group, relative to that for the cases, the greater
the apparent protection. Many reports have documented that the women who
are at highest risk of developing cervical cancer have infrequent or no
smears. Therefore estimates of relative risk will be strongly confounded
by the difference in uptake rates between the cases and controls.
Conclusions and Recommendations
In light of the foregoing considerations, it
is difficult to formulate frequency recommendations that have solid scientific
validity. On an observational basis all that can be said is that women
who are presently being screened regularly have a very low rate of developing
cervical cancer, whereas those who are being screened infrequently or not
at all, have a much higher risk of developing the disease. In the British
Columbia cohort study only 4% of cases of carcinomas in situ or worse were
detected by smears subsequent to a third smear.<2>
There is fair evidence to include Papanicolaou smears in the periodic health examination of women who have been sexually active (B Recommendation). The Task Force concurs with the Workshop’s recommendations concerning frequency of smears once central laboratories are operational. Until such time, it recommends that high-risk women be screened more frequently than every 3 years since the false negative rate may run well above 25%, and the disease progression rate is known to vary. Physicians should keep in mind, however, that these high-risk women constitute a small proportion of the population.
Because some social stigma may be attached to being labelled as being at high risk, individual physicians should consider informing a patient of the risk factors and allowing her to make the decision on the appropriate frequency of screening.
The Task Force emphasizes that the largest group of women at greatest risk of dying from cervical cancer are those who have never been screened. The majority of these are women over 50, particularly native women and women who have immigrated from poorer countries. It is more important that these women be screened, even if only once, than that average or low-risk women be screened frequently.
Unanswered Questions (Research
Agenda)
Research into methodologies to reach women who
have never been screened is critical. In future, most women reaching middle-age
will have had many cervical smears and may therefore be at a different
risk than the average middle-aged or older woman is at present. Most will
have had nothing but negative smears. It is important to determine if,
in well tested women, a history of numerous negative smears is associated
with a substantially reduced risk.
Evidence
The evidence used in this review was taken from
the collection of the author. This review was initiated in June 1989 and
the recommendations were finalized by the Task Force in January, 1992.
A technical report with a full reference list dated February 1992 is available
upon request.
Full Citation
Morrison BJ. Screening for cervical cancer. In:
Canadian Task Force on the Periodic Health Examination. Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994; 870-881.