Research

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ONCOLOGY

Risk of invasive cervical cancer in relation

to management of abnormal Pap smear results
Lena Silfverdal, MD; Levent Kemetli, MSci; Bengt Andrae, MD; Pr Sparn, PhD; Walter Ryd, MD, PhD;
Joakim Dillner, MD, PhD; Bjrn Strander, MD, PhD; Sven Trnberg, MD, PhD
OBJECTIVE: We sought to evaluate the management of women with

abnormal cytology in terms of subsequent risk of invasive cervical

cancer.
STUDY DESIGN: The screening histories of all invasive cervical cancer

cases diagnosed in Sweden 1999-2001 and of 5 population-based

controls per case were reviewed. In all, 159 patients and 258 control
subjects aged 67 years had an abnormal smear result 0.5-6.5 years
prior to cancer diagnosis. The cervical cancer risk was estimated in
relation to management by calculating odds ratios.
RESULTS: Histologic assessment of low-grade squamous abnormali-

ties strongly reduced the risk compared to repeated cytology (odds

ratio, 0.46; 95% confidence interval, 0.24-0.89). Delaying histologic

assessment was also associated with a higher risk (odds ratio, 5.65;
95% confidence interval, 1.39-23.05). After high-grade squamous
atypia, absence of any cytologic or histologic specimen was a major
determinant of cancer risk (odds ratio, 12.52; 95% confidence interval,
1.42-infinitive).
CONCLUSION: For adequate protection against invasive cervical can-

cer, further assessment with histology must be recommended also for

women with low-grade squamous abnormalities.
Key words: cervical cancer risk, histologic assessment, management
of abnormal Pap smear results, population-based case control study,
repeated cytology

Cite this article as: Silfverdal L, Kemetli L, Andrae B, et al. Risk of invasive cervical cancer in relation to management of abnormal Pap smear results. Am J Obstet
Gynecol 2009;201:188.e1-7.

ervical cancer screening by cytology

aims at detection and removal of
precursor lesions and has been highly effective in reducing the incidence of cervical cancer.1 Although nonparticipaFrom the Department of Obstetrics and
Gynecology (Dr Silfverdal), Ume
University Hospital, Ume; Cancer
Screening Unit, Oncologic Center,
Karolinska University Hospital, Stockholm
(Mr Kemetli and Dr Trnberg); Department
of Obstetrics and Gynecology, Gvle
Hospital, Gvle (Dr Andrae); Department of
Medical Epidemiology and Biostatistics,
Karolinska Institute, Stockholm (Dr
Sparn); Department of Pathology and
Clinical Cytology (Dr Ryd) and Oncologic
Center (Dr Strander), Sahlgrenska
University Hospital, Gteborg; and
Department of Medical Microbiology, Lund
University, Malm University Hospital,
Malm (Dr Dillner), Sweden.
Received Oct. 1, 2008; revised Jan. 24, 2009;
accepted April 10, 2009.
Reprints not available from the authors.
Funded by the Swedish Cancer Society.
0002-9378/$36.00
2009 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2009.04.006

188.e1

tion in screening has been found to be

the major reason for the remaining morbidity and mortality caused by cervical
cancer,2-5 a substantial proportion (3670%) of previously screened women
with invasive cervical cancer are reported to have had abnormal smear findings 6 months prior to the cancer diagnosis.3,6 In a recent nationwide audit
of the Swedish cervical cancer screening
program, 32% of the women with invasive cervical cancer who were screened
within the recommended intervals had a
prediagnosis abnormal smear finding,
and this was associated with a 7-fold increased risk compared to having had
normal cytology.5 Therefore, the question why women still develop invasive
cervical cancer despite having had abnormal smear results detected at screening needs to be investigated. To our
knowledge, there are no other studies on
this issue that have used a nationwide,
population-based study design.
From 4-13% of women with invasive
cervical cancer have been reported to
have had inadequate management of abnormal smear results.2,4 Although there
is a consensus on the management of

American Journal of Obstetrics & Gynecology AUGUST 2009

women with high-grade squamous and

with nonsquamous cytologic lesions, ie,
histologic assessment,7,8 controversies
remain about the most effective way to
manage the larger number of women
with low-grade cytologic abnormalities.9
Cytologic surveillance or colposcopy
and biopsy, possibly conditional on a
positive human papillomavirus test result, are the main strategies. The psychological and physical morbidity of colposcopy and biopsy, the risk of overtreatment,
overloading of colposcopy clinics, and
high costs have been arguments in favor of cytologic surveillance. On the
other hand, concern about the risk of
drop out from cytologic surveillance,
increased risk of invasive cancer and of
underlying high-grade lesion already
existing, as well as increased anxiety
during cytologic surveillance, have favored a policy of colposcopy and
biopsy.
The aim of this study was to evaluate
the management of women with an abnormal Papanicolaou (Pap) smear finding in terms of subsequent risk of invasive cervical cancer using a nationwide
and population-based study design.

Oncology

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FIGURE

Flow chart describing the study groups

Age > 66
y
n = 370

Cases
n = 1,230

Age > 66
y
n = 1,845

Controls
n = 6,124

No Pap
smear
n = 288

Age < 67
y
n = 860

No Pap
smear
n = 710

Age < 67
y
n = 4,279

Benign
smear
n = 413

Pap smear
n = 572

Benign
smear
n = 3,311

Unsatisfactory
for evaluation, n = 22

Atypical
smear
n = 137

Low
grade
n = 64

Nonsquamous
n = 49

High
grade
n = 24

Unsatisfactory
for evaluation, n = 84

Low
grade
n = 110

High
grade
n = 34

Pap smear
n = 3,569

Atypical
smear
n = 174

Nonsquamous
n = 30

Flowchart illustrating data generation process for case subjects having primary epithelial invasive
cervical cancer and their respective control subjects. Study groups are below broken line and
included case and control subjects with first abnormal smear finding being atypical or unsatisfactory
for evaluation 0.5-6.5 years before case subjects cancer diagnosis.
Silfverdal. Risk of invasive cervical cancer in relation to management of abnormal Pap smear results. Am J Obstet Gynecol
2009.

M ATERIALS AND M ETHODS

The study is based on a nationwide audit
of the Swedish cervical cancer screening
program.5 The audit included 1230 patients from the Swedish National Cancer
Registry with a primary epithelial invasive cervical cancer diagnosed between
Jan. 1, 1999, and Dec. 31, 2001, and 6124
age-matched control women, randomly
selected from the national population
register, alive at the date of the patients
cancer diagnosis and without previous
diagnosis of invasive cervical cancer. Details on the identification of patients and
control subjects in the audit have been
reported elsewhere.5
In this study we included the 159 case
women and the 258 control women who

had an abnormal Pap smear finding registered 0.5-6.5 years before the date of the
patients cancer diagnosis and who were
aged 67 years. Age 67 years was chosen to only include the recommended
screening ages plus recently tested women
aged 60 years. The longest time for
which nationwide data were available was
6.5 years. A test that had been taken within
6 months before the date of the cancer diagnosis was not considered as part of the
screening history but rather as a test leading to the detection of invasive cancer. The
Figure illustrates how the study groups
were derived and subdivided into those
with a primary abnormal smear result being low-grade atypia, high-grade atypia,
nonsquamous atypia, or unsatisfactory for

Research

evaluation (for definitions, see the

following).
All 7 regional ethical review boards in
Sweden approved the study.
Data on the cervical cytology and histology were obtained from the National
Cervical Cancer Screening Register for
Quality Control. The register has collected data from all 30 histopathologic/
cytologic laboratories in Sweden, but as
some laboratories had not kept all older
data, the completeness of the registry was
90% for the cytology and the histology in
1991-1993, and 98% for the cytology and
96% for the histology in 1994-2001. The
following data were available: age at cancer diagnosis, cytologic and histologic
history in terms of date, cytologic and
histopathologic diagnoses, and analyzing laboratory 0.5-6.5 years prior to the
cancer diagnosis. All smears were classified into 5 categories, ie, normal, unsatisfactory for evaluation, low-grade
squamous abnormality, high-grade
squamous abnormality, and nonsquamous abnormality. Normal was defined as the absence of atypia, and abnormal as the presence of atypia or
koilocytosis, or being unsatisfactory for
evaluation. The cytologic diagnoses in
the categories low-grade, high-grade,
and nonsquamous are shown in Table 1.
When 1 cytologic diagnosis had been
present the most severe was considered
as the main diagnosis. Severity was
ranked as follows: koilocytosis, atypical
squamous cells of undetermined significance (ASCUS), cervical intraepithelial
neoplasia (CIN) grade 1 (CIN1), atypia
in cells of uncertain origin, glandular cell
atypia, CIN2, CIN3, and adenocarcinoma in situ. Low-grade represented
the diagnoses requiring repeated smears
as a minimum management, and highgrade and nonsquamous represented
those requiring colposcopy and biopsy,
according to guidelines made by the
Swedish Society of Obstetrics and
Gynaecology Working Group for Cervical Cancer Prevention.10
The first abnormal smear finding was
identified, and then all smears within the
following 25 months. All cervical histology
that had been registered within 25 months
after the reported abnormal smear result
was identified, but histology registered

AUGUST 2009 American Journal of Obstetrics & Gynecology

188.e2

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TABLE 1

Odds ratio for invasive cervical cancer in women assessed with cytology only,
or with histology, or having no morphology registered
Diagnosisa

Category

Assessmentb

Case

Koilocytosis

Cytology only

1.00

Reference

Histology

1.88

(0.04-82.80)

No morphology

1.58

(0.03-99.09)

Control

OR

(95% CI)

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

ASCUS

Cytology only

15

20

1.00

Reference

Histology

18

0.68

(0.24-1.96)

No morphology

1.78

(0.34-9.18)

Cytology only

19

23

1.00

Reference

Histology

11

40

0.33

(0.13-0.81)

4.36

(0.45-Infinitive)

Cytology only

35

45

1.00

Reference

Histology

21

59

0.46

(0.24-0.89)

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

CIN1

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................
c

No morphology

................................................................................................................................................................................................................................................................................................................................................................................

Total low-grade squamous

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................

No morphology

1.71

(0.54-5.38)

Cytology only

1.00

Reference

Histology

25

0.29

(0.06-1.44)

No morphology

8.75

(0.94-Infinitive)

Cytology only

1.00

Reference

Histology

No morphology

Cytology only

................................................................................................................................................................................................................................................................................................................................................................................

CIN2

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................
c

................................................................................................................................................................................................................................................................................................................................................................................

CIN3/cancer in situ

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Total high-grade squamous

1.00

Reference

...........................................................................................................................................................................................................

Histology

29

0.39

No morphology

11

12.52

(0.09-1.77)

Cytology only

14

1.00

Reference

1.42

(0.27-7.52)

...........................................................................................................................................................................................................
c

(1.42-Infinitive)

................................................................................................................................................................................................................................................................................................................................................................................

Glandular cell atypia

...........................................................................................................................................................................................................

Histology

...........................................................................................................................................................................................................

No morphology

0.35

(0.08-1.60)

Cytology only

1.00

Reference

Histology

10

0.23

(0.04-1.38)

No morphology

0.76

(0.05-11.97)

1.00

Reference

................................................................................................................................................................................................................................................................................................................................................................................

Atypia in cells of uncertain origin

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Adenocarcinoma/adenocarcinoma in situ

Cytology only

Histology

No morphology

Cytology only

22

Histology

19
8

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Total nonsquamous

1.00

Reference

14

0.50

(0.17-1.46)

0.39

(0.11-1.42)

...........................................................................................................................................................................................................
...........................................................................................................................................................................................................

No morphology

................................................................................................................................................................................................................................................................................................................................................................................

ASCUS, atypical squamous cells of undetermined significance; CI, confidence interval; CIN, cervical intraepithelial neoplasia; H, high-grade squamous abnormality; L, low-grade squamous
abnormality; N, nonsquamous abnormality; OR, odds ratio.
a

Diagnosis of first abnormal smear finding 0.5-6.5 years prior to patient cancer diagnosis; b assessment within 25 months after first abnormal smear finding; c OR and CI estimated using exact
method.

Silfverdal. Risk of invasive cervical cancer in relation to management of abnormal Pap smear results. Am J Obstet Gynecol 2009.

within 60 days prior to the cancer diagnosis was excluded, so as not to include assessments having led to the detection of an
invasive cancer. The initial assessment of
188.e3

the first abnormal smear finding and the

following assessments within 25 months
from the date of the first abnormal smear
finding were investigated. The date of the

American Journal of Obstetrics & Gynecology AUGUST 2009

first repeated cytology, and/or histopathology, was considered as being the first
further assessment visit. If the laboratory
registration dates of cytology and histopa-

Oncology

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Research

TABLE 2

Age at first atypical smear and time from first atypical smear to date of cancer diagnosis among cases
Category low-grade

Category high-grade

Category nonsquamous

Cases
Controls P
Cases
Controls P
Cases
Controls P
(n 64) (n 110) value (n 24) (n 34) value (n 49) (n 30) value
Mean age at first abnormal smear finding (y)

38.1

37.5

.680

38.3

36.6

.469

42.4

45.1

.243

Mean time from first abnormal smear finding (mo) 41.5

47.0

.124

36.1

45.8

.132

30.0

42.0

.015

................................................................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Silfverdal. Risk of invasive cervical cancer in relation to management of abnormal Pap smear results. Am J Obstet Gynecol 2009.

thology were 8 days apart, they were

considered to belong to the same visit. The
date of a following repeated cytology
and/or histopathology was considered as
being the second visit, and so forth.
We analyzed each category of abnormality regarding type of further assessment at each visit, ie, with cytology only
or with histopathology included, or having no further cytology or histology registered (no morphology), and time
from the date of the first abnormal smear
finding to the assessments. A t test was
used for testing equality of means. To assess the risk of cervical cancer for different exposures, odds ratio (OR) with 95%
confidence interval was calculated in logistic regression models, controlling for
age at first abnormal smear result.

R ESULTS
The mean age at the date of the first abnormal smear finding, and the mean
time from first abnormal smear finding
to the date of the cases cancer diagnosis,
are shown in Table 2.

Category low-grade
The ORs for invasive cervical cancer in
women assessed with histology, or with no
morphology registered, compared to re-

peated cytology are presented in Table 1.

Assessment with histology was associated
with a significantly lower risk of invasive
cancer than repeated cytology only (OR,
0.46; 95% confidence interval, 0.24-0.89).
The numbers under each cytologic diagnosis are small and significant correlation
was only found in CIN1.
In the majority of cases and controls
with histology, the specimen had been
taken at first visit (14/21 cases and 44/59
controls). Having had the histology
taken after 7-12 months, compared to
within 6 months, was associated with a
higher risk (Table 3). As an indication of
completeness of follow-up we estimated
the proportion of women who had a
first, second, and third visit with cytology or histology registered, and the proportion of cases with no first-visit morphology was 12.5% (8/64), with no
second-visit morphology was 46.9% (30/
64), and with no third-visit morphology
was 71.9% (46/64) (data not shown).
The corresponding figures for controls
were 5.4% (6/110), 29.1% (32/110), and
59.1% (65/110).
Assessment with repeated cytology
only did not differ significantly from no
morphology at all in terms of cancer risk

(Table 1). Among women under cytologic surveillance only (data not shown),
the mean number of repeated smears
was similar between cases and controls
(1.69 vs 1.78; P .635), and we found no
clear difference regarding the proportions having presented with 2 normal,
and no atypical, smear results: 28.6%
(10/35) vs 37.8% (17/45); (OR, 0.66;
95% confidence interval, 0.25-1.7).

Categories high-grade
and nonsquamous
After a high-grade squamous atypia, the
absence of morphology strongly increased the risk for invasive cancer (Table 1). The decreased risk with histologic
assessment, compared to cytology, was
not statistically significant.
Among nonsquamous abnormalities,
we found a tendency toward decreased risk
with histology, compared to repeated cytology, although not statistically significant
(Table 1). Repeated smear was not associated with a lower risk compared to absence
of morphology.
The majority of the histologically assessed cases and controls with a highgrade or a nonsquamous atypia had the
biopsy specimen taken at the first visit
(21/28 cases and 33/43 controls). The

TABLE 3

Odds ratios for invasive cervical cancer in women assessed with histology at different time periods
Category low-grade
a

Time period for assessment

Case

Control

Histology within 6 mo

Categories high-grade and nonsquamous

OR

(95% CI)

Case

Control

OR

(95% CI)

13

49

1.00

Reference

23

40

1.00

Reference

Histology 7-12 mo

5.65

(1.39-23.05)

2.61

(0.41-16.78)

Histology 13-25 mo

1.26

(0.23-6.97)

3.48

(0.30-40.49)

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

CI, confidence interval; OR, odds ratio.

a

Assessment after first atypical smear 0.5-6.5 years before patient cancer diagnosis.

Silfverdal. Risk of invasive cervical cancer in relation to management of abnormal Pap smear results. Am J Obstet Gynecol 2009.

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Oncology

proportion of cases with no morphological assessment at all was 26.0% (19/73),

with no second-visit morphology was
47.9% (35/73), and with no third-visit
morphology was 74.0% (54/73) (data
not shown) The corresponding figures
for controls were 12.5% (8/64), 28.1%
(18/64), and 45.3% (29/64).

Smears unsatisfactory for evaluation

In this category we found no significant
differences between cases and controls in
the further assessment (data not shown).
Within 13 months 77.3% of cases (17/
22) and 67.9% of controls (57/84) (OR,
1.61; 95% confidence interval, 0.54-4.83)
had been assessed, including 2 cases and
10 controls with histology.

C OMMENT
The main finding in our study was that
histologic assessment was strongly associated with a decreased risk of invasive
cervical cancer compared to repeated cytology in women with a low-grade squamous abnormal smear result. As expected, absence of morphological
assessment strongly increased the risk in
women with a high-grade squamous
atypia.
The study has several strengths. The
cases were identified from a study base
comprising all new cases of invasive cervical cancer that occurred in Sweden
during a 3-year period, and their histopathological specimens had been rereviewed. Both cases and controls come
from the same study base, as defined by
very accurate national population registers.11 The access rate to data from all
eligible cases and controls was estimated
to be least 93%, as the data on cytology
and histopathology were collected from
a national database of high quality, with
data lacking only from some laboratories
and for only half a year or at most a few
years.
Limitations to the study are the fact
that the statistical power was limited,
particularly for some rare diagnoses; our
matching on age at diagnosis rather than
on screening histories; and the lack of
data on colposcopical examination.
However, despite the limited power,
some strong associations were observed.
The age differences between cases and
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www.AJOG.org
controls at first abnormal smear finding
were negligible and adjusted for in the
analysis (Table 2). A difference in time
from first abnormal smear result to diagnosis of cancer among the cases would
make the results less reliable if the controls had shorter intervals than the cases,
because they would then have had less
time to develop invasive cancer. In this
study the time intervals were longer for
the controls (Table 2), which supports
the results indicating a protective effect
by the management of controls. In the
categories low-grade and nonsquamous
abnormality the proportions of the different cytologic diagnoses were equal at
the primary abnormal smear finding
(Table 1). In category high-grade there
was a larger proportion of CIN3 among
the cases, which means that the results in
this category should be interpreted with
caution. No information on whether or
not colposcopies had been done was
available. The occurrence of colposcopical examinations where no biopsy or cytology is taken among the no-morphology subjects might explain the finding
that no morphology and cytology
only were equivalent in terms of risks in
the categories low-grade and nonsquamous. However, colposcopy not accompanied by a repeated smear or a biopsy is
not likely to have occurred to any appreciable extent, as it is not recommended
practice and not in accordance to traditional practice in Sweden. Therefore, it is
likely that there had been no further assessment when no morphology had been
registered.
Differences between cases and controls in the management were expected.
Sasieni et al3 reported that 13% of the
cases and 1% of the controls had encountered inadequate assessment in a
case-control study on smear histories of
women aged 70 years with cervical
cancer. In the same study, no significant
difference was found between the proportions of cases and controls with an
abnormal smear result followed by 2
negative results. This lack of protective
effect even by 2 normal smear results after a low-grade abnormal smear result is
in concordance with our findings. In the
present study we chose a different approach from previous publications, by

American Journal of Obstetrics & Gynecology AUGUST 2009

comparing the management of abnormal smear findings in cases and controls

irrespective of what the adequate management according to approved guidelines would be.
Despite the lack of similar case-control
studies, our results, suggesting biopsy to
be more effective than repeated cytology
in women with low-grade squamous abnormalities, are nevertheless supported
by results from other studies. Highgrade dysplasia has been found in
11-36% of women presenting with a single smear of ASCUS,12,13 and in 31-49%
of women with CIN1,14,15 indicating
that relying on cytology is insufficient.
Soutter and Fletcher16 showed, in a reanalysis of long-term studies, that
women with low-grade abnormal smear
findings who had been surveyed cytologically had a 16-47 times higher incidence
of invasive cancer than the general population. In a Norwegian study, women
with ASCUS followed by a normal smear
finding were at increased risk of invasive
cancer within a 7-year follow-up
period.17
Although randomized trials comparing colposcopy vs cytologic surveillance
of ASCUS and low-grade CIN have demonstrated similar levels of detection of
CIN3 within 2 years,18-21 the high nonattendance rate (20-25%) in women under cytologic surveillance reported from
2 studies,18,19 gave rise to a major concern about the efficiency and the longterm outcome. Our findings, of successive loss to follow-up after each visit
among cases as well as controls, are in
concordance with the results of a recent
metaanalysis of randomized trials, showing that compliance with cytologic surveillance declines over time in women
with low-grade cytologic abnormalities.22 These findings underline the importance of diagnostic assessment with
biopsy at the first visit.
Our results suggest also an increased risk
when the biopsy is delayed 7-12 months
after a first low-grade abnormal smear
finding. This is supported by the results of
others showing a low, but not negligible,
risk of being diagnosed with invasive cancer within 24 months after a low-grade abnormality (ASCUS 0.25%; low-grade
squamous intraepithelial lesion 0.15%).23

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Another important aspect of delayed assessment is the negative psychological side
effect of not knowing whether one is
healthy or ill. It has been shown that the
intermediary period between the notification of an abnormal smear result and the
clarification of the nature and the degree of
the pathological findings is particularly
stressful for many women.24
In the categories high-grade and
nonsquamous abnormalities, the expected management according to guidelines would be histologic assessment,10
and therefore the low rate of biopsy in
controls with a nonsquamous atypia
(47%) was unexpected and indicates a
poor adherence to guideline recommendations. Women presenting with glandular cell atypia have been found to have
underlying invasive disease in 4-16% and
preinvasive disease in 17-40%,25,26 and
therefore colposcopy and histologic investigation has been recommended.7,8,25,26
It is well known that women with highgrade squamous abnormalities in cytology
have a high rate of underlying CIN2-3 (7790%)27 and a substantial risk of developing
an invasive cancer within 24 months
(1.44%).23 The results of the current study
suggest that there is a substantial risk of developing invasive disease when women in
this category are not further assessed. Assessment with cytology only occurred
rarely and only in women with CIN2.
In women having a first nonnormal
smear finding unsatisfactory for evaluation, our finding of no correlation between
further assessment and prevention of invasive disease is in disagreement with the results presented by Nygrd et al,28 something that could be explained by the
smaller numbers in our study. Nygrd et
al28 reported an increased hazard ratio of
invasive cervical cancer for women with an
unsatisfactory smear, which was mostly attributable to women who did not have a
repeated smear within 2 years.
Our finding, showing that cytologic
surveillance of women with low-grade
squamous cytologic abnormalities is less
protective than biopsy, should have implications for guidelines. This means a
need of increased colposcopy resources.
As human papillomavirus-DNA testing
has shown to be efficient in triaging
women with ASCUS, this could be used

to counteract an increased need of colposcopy services.29 The finding of a

highly increased risk for invasive disease
after a high-grade squamous atypia without morphological follow-up implies
that there is a need for a reliable system of
notification of missed cases and of reinvitation to investigation.
In this study, it is unknown to which extent the histologically assessed women also
had received treatment, and if the histologic specimens had been taken as punch
biopsies, endocervical curettages, or cone
biopsies. Neither do we know about the extent and quality of colposcopical evaluations. Further studies are needed to assess
the association between these aspects and
risk of invasive cervical cancer.
In conclusion, the results from the current study indicate that to improve the efficiency of cervical cancer screening, further assessment with histology should also
be recommended for women with lowgrade squamous abnormal smear findings,
and that organized systems of notification
of missed cases and of reinvitation to investigation could have significant cancerpreventive gains.
f
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