Postcolposcopy Management of

Women With Histologically Proven

CIN 1: Results From TOMBOLA

Mahalakshmi Gurumurthy, MRCOG,1 Seonaidh C. Cotton, BSc, MLitt, PhD,2

Linda Sharp, BSc(Hons), MSc, PhD,3 Louise Smart, MD, FRCPath,4
Julian Little, MA PhD,5 Norman Waugh, MCRP(UK), MPH, FFPHM,6
and Margaret E. Cruickshank, MD, FRCOG2
1
Gynaecological Oncology, University Hospital of Llandough, Wales; and 2University of
Aberdeen, Aberdeen, United Kingdom; 3National Cancer Registry Ireland, Cork, Ireland;
4
Aberdeen Royal Infirmary, Aberdeen, United Kingdom; 5Department of Epidemiology and
Community Medicine, University of Ottawa, Ottawa, Canada; and 6Warwick Medical School,
Coventry, United Kingdom

h Abstract Materials and Methods. This is an ad hoc analysis of

Objectives. This study aimed to determine during
36 months of follow-up the (1) clinical outcomes and (2)
influence of high-risk human papillomavirus (HPV) status on
the risk of progression to cervical intraepithelial neoplasia
2+ (CIN 2+), among women with histologically proven CIN 1.
The authors have declared they have no conflicts of interest.
The work was supported by the Medical Research Council (G9700808)
and the NHS in England and Scotland.
Institutions where study was carried out: Aberdeen, Nottingham, and
Dundee in the United Kingdom.
Reprint requests to: Mahalakshmi Gurumurthy, University Hospital of
Llandough, Penlan Rd, Penarth, CF64 2XX. E-mail: m.gurumurthy@nhs.net
M.G. contributed in the critical review of the literature and writing of
the article.
S.C. contributed in the collection and analysis of the data with statistical
input and critical analysis of the article.
L.Sh. contributed in the analysis of the data, statistical input, and critical
analysis of the article.
L.Sm. contributed in the critical analysis and writing of the article.
J.L. contributed in the data interpretation and critical revision of the
manuscript.
N.W. provided comments on the drafts and was also the chief investi-
gator for TOMBOLA 2003Y2010.
M.E.C. conceived the original design, advised on the analysis and in-
terpretation of the data, and wrote the article.
All authors approved the final version of the article.
Ethical approval was obtained from the Joint Research Ethics Committee
of NHS Grampian and the University of Aberdeen (Reference 970072), the
Tayside Committee on Medical Research Ethics (170/99) and the Nottingham
Research Ethics Committee (PA129701).
Trial registration: ISRCTN 34841617 (http://www.isrctn.org/).
women with CIN 1 within TOMBOLA, a randomized trial of
the management of women with low-grade cervical cy-
tology. Women from the colposcopy arm with CIN 1 con-
firmed on punch biopsies and managed conservatively by
cytology every 6 months in primary care were included.
Sociodemographic data and a sample for HPV testing were
collected at recruitment. Data on the sample women were
extracted to calculate the cumulative incidence of CIN 2+
and the performance characteristics of the baseline HPV
test. Detection of CIN 2 or worse (CIN 2+) during follow-up
or at exit colposcopy was analyzed.
Results. A total of 171 women were included. Their me-
dian age was 29 years. Fifty-two percent were high-risk HPV
positive, 17% were HPV-16 positive, and 11% were HPV-18
positive. Overall, 21 women (12%) developed CIN 2+, with a
median time to detection of 25 months. Factors associated
with progression to CIN 2+ were presence of HPV-18 (relative
risk = 3.04; 95% CI = 1.09Y8.44) and HPV-16 and/or HPV-18 at
recruitment (relative risk = 3.98; 95% CI = 1.60Y9.90). The
sensitivity and specificity of a combined HPV-16/HPV-18 test
for the detection of CIN 2+ during 3 years were 58% and
78%, respectively.
Conclusions. Our results suggest that women with
confirmed CIN 1 have low rates of progression to high-
grade CIN within 3 years. Because the median time to
progression was 25 months, conservative management
could recommend the next repeat cytology at 2 years. h

Ó 2014, American Society for Colposcopy and Cervical Pathology Key Words: cervical intraepithelial neoplasia, CIN, low-grade
Journal of Lower Genital Tract Disease, Volume 18, Number 3, 2014, 203Y209 abnormalities, colposcopy, human papillomavirus (HPV)

Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
204 & GURUMURTHY ET AL.
H igh-grade cervical intraepithelial neoplasia (CIN)
has a significant risk of progressing to invasive
cancer, but the natural history of low-grade CIN (CIN 1)
is less well understood. Although the risk of progression
to cancer seems to be low, most studies have been based
on women with low-grade abnormal cytological finding
rather than histologically confirmed CIN 1 [1, 2], and
these results have been extrapolated to support conser-
vative management of CIN 1 with cervical cytology
every 6 months. Current National Health Service (NHS)
Cervical Screening Programme guidelines advocate that
women with CIN 1 do not require treatment and can be
followed up by cytological surveillance until regression
is confirmed or treatment is undertaken for persistence
or progression [3]. However, there is limited published
evidence confined to women with histologically proven
CIN 1. Small cohort studies support conservative man-
agement of CIN 1 because the risk of progression to
high-grade CIN or cancer is low [4Y6]. In the United
States, the ASCUS LSIL Triage Study (ALTS) reported
that 12% of women with CIN 1 or less developed high-
grade CIN by 2 years of follow-up [7, 8].
Detection of high-risk (HR) human papillomavirus
(HPV) DNA status for women with low-grade cytology
could provide a means of predicting progression or
regression and could be used to determine intensity of
follow-up. In this article, we use data from the UK
TOMBOLA trial to examine the relationship between
HR HPV and progression of cervical changes in women
with histologically confirmed CIN 1 during a 3-year
period and to assess the properties of a single HPV test in
the management of these women.
MATERIALS AND METHODS
TOMBOLA was a prospective randomized trial of
the management of women with borderline or mildly
dyskaryotic cytology nested within the UK cervical
screening programs. The TOMBOLA trial design is de-
scribed in detail elsewhere [9]. Brief details specific to
this analysis are described here.
Women aged 20 to 59 years with a recent cervical cy-
tology test showing mild dyskaryosis or borderline nu-
clear abnormalities (BNA) and up to 1 additional BNA
smear in the previous 3 years were eligible to take part in
TOMBOLA. They were invited to attend a recruitment
appointment and, after informed consent was obtained,
provided a cervical swab for HPV testing and completed a
brief sociodemographic and lifestyle questionnaire. The
cervical swab taken at recruitment was subject to testing
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
for 14 HR HPV types using GP5+/6+ methodology and
also for HPV-16 and HPV-18 individually using type-
specific primers [10].
Women were subsequently randomized to a policy of
cytological surveillance or initial colposcopy. Women
who attended for colposcopy were further randomized
to a policy of immediate treatment or punch biopsy, with
2 to 4 punch biopsies, and recalled for treatment only if
these showed CIN 2 or more severe disease (CIN 2+).
This analysis includes women who had punch biopsy
with histologically confirmed CIN 1. This group was
subsequently managed by cytology tests every 6 months
in primary care, with referral back to colposcopy if sub-
sequent cytology was reported as high-grade dyskaryosis.
Approximately 3 years after recruitment, women were
invited to attend an exit colposcopy examination and had
treatment using large loop excision of transformation
zone if an abnormal transformation zone was identified
colposcopically.
In line with the pragmatic nature of TOMBOLA,
all histology samples were read in NHS histopathology
laboratories, which participated in national Quality As-
surance schemes. In addition, 1 or 2 independent pa-
thologists centrally reviewed histology samples from a
random sample of 272 participants. The review diagnosis
was identical to the original diagnosis in 252 cases. The
J was 0.9, indicating good agreement.
We computed the cumulative incidence of CIN 2+
during follow-up and at the exit examination, to provide
a measure of the absolute risk of progression. In the
calculation of cumulative incidence, to take account of
variation between women in the length of follow-up,
each woman accrued person years from the date of the
punch biopsy showing CIN 1 until the date of their exit
examination for those who attended or, for others, the
date the exit appointment was scheduled, they requested
to leave the trial, they had a hysterectomy, they died, or
they moved out of the area.
We compared cumulative incidence between groups
(defined by HPV status at recruitment and a range of
sociodemographic [including age, smoking status, etc.]
and cytology-based [e.g., smear history] factors) by
calculating relative risks using Poisson regression.
The performance characteristics of a single HPV test
at baseline (sensitivity, specificity, positive [PPV] and
negative [NPV] predictive values) for the prediction of
progression to CIN 2+ during 3 years were also calcu-
lated. This was done separately for a test for (a) multiple
(i.e., 14) HR HPV types; (b) HPV-16; (c) HPV-18; and
(d) a combination of HPV-16 and HPV-18.
 Postcolposcopy Management of CIN 1 & 205

A sensitivity analysis was conducted, which included Table 2. HPV Status at Recruitment
women who had either attended their exit examination Negative Positive
and/or had had CIN 2+ detected during follow-up.
HR HPV types 75 (48.4%) 80 (51.6%)
HPV-16 129 (83.2%) 26 (16.8%)
HPV-18 138 (89.0%) 17 (11.0%)
HPV-16 and HPV-18 153 (98.7%) 2 (1.3%)
RESULTS HPV-16 and/or HPV-18 114 (73.5%) 41 (26.5%)
This analysis includes 171 women with histologically
HPV indicates human papillomavirus; HR, high risk.
confirmed CIN 1 on punch biopsy. Just more than half
of the women were aged 20 to 29 years, one quarter
Default
were aged 30 to 39 years, and the reminder were aged
40 to 59 years (see Table 1). At recruitment, 47% of Ten percent of the women (17/166 with more than
women had BNA cytology, and the reminder had mild 1 year of follow-up) were classified as defaulters. We
dyskaryosis. Forty-five percent had never smoked, 42% defined persistent defaulters as women who failed to
were current smokers, and 13% were ex-smokers. Ap- attend for 2 consecutive cytology tests.
proximately one third of women were oral contraceptive
pill users. CIN 2+ During Follow-up or at Exit Colposcopy
Twenty-one women (cumulative incidence 4.8 per 100
person years) developed CIN 2+ during follow-up in-
HPV Status at Recruitment cluding the exit colposcopy examination (13 cases of
Table 2 shows the HPV status of women at recruitment. CIN 2+ were detected during follow-up and 8 cases at
Sixteen women (9%) either declined to provide a sample the exit examination). Thirteen women developed CIN
for HPV testing or had inadequate sample for the anal- 2, and the remaining 8 developed CIN 3. There were no
ysis. Of the remainder, just more than half tested positive cases of invasive cancer. The median time to diagnosis
for HR HPV types. Seventeen percent of the women of CIN 2+ (from the date of biopsy showing CIN 1 to
tested positive for HPV-16, and 11% tested positive for date of CIN 2+) was 25 months (749 days; interquartile
HPV-18. Two women were positive for both HPV-16 range = 554Y1,014 days). The median time to diagnosis
and HPV-18 at recruitment. of CIN 3 (from the date of biopsy showing CIN 1 to
date of CIN 3) was 19 months (577 days; interquartile
range = 474Y763 days).
Table 1. Sociodemographic Characteristics of Sample Of the 21 women with CIN 2+, the HPV status at
n % recruitment was unknown for 2. Thirteen were HR HPV
positive, and 6 were HR HPV negative; 6 were positive
Age, y
20Y29 86 50.3 for HPV-16, and 5 were positive for HPV-18.
30Y39 42 24.6 Of the eight women who developed CIN 3 disease, all
40Y49 33 19.3
50Y59 10 5.9
but one was detected before the exit colposcopy exam-
Median age, y 29 (interquartile ination. Of these 8 women, the HPV status at recruit-
range = 23Y40)
ment was unknown for 2. Of the remainder, 5 were HR
Smear status
Single mild 82 48.0 HPV positive at recruitment, and 1 was HR HPV neg-
Mild with previous BNA (including BNA/mild 9 5.3 ative; 3 were positive for HPV-16, and 1 was positive
and mild with history)
Single BNA 57 33.3 for HPV-18.
BNA with previous BNA (including BNA/BNA 23 13.5
and BNA with history)
Smoking status Factors Associated With Progression to CIN 2+
Never smoker 77 45.3
Ex-smoker 22 12.9 The only factors significantly associated with an increased
Current smoker 71 41.8 risk of CIN 2+ during follow-up was infection with HPV-
Missing 1 -
Current use of hormonal contraception
18 (relative risk = 3.04; 95% CI = 1.09Y8.44) and HPV-16
No 98 57.3 and/or HPV-18 at recruitment (relative risk = 3.98; 95%
Injection, implants, intrauterine system 19 11.1
CI = 1.60Y9.90; see Table 3). Infection with HPV-16 alone
Oral contraceptives 54 31.6
was associated with a 2.3-fold raised risk, but this did not
BNA indicates borderline nuclear abnormalities. reach statistical significance. Other factors (age, smoking

Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
206 & GURUMURTHY ET AL.

status, recruitment cytology, use of hormonal contra- have a low rate of progression to CIN 2+. During
ception, and reproductive history) were not significantly 3 years, 12% of women developed CIN 2+ (cumulative
associated with progression. incidence 4.8 per 100 person years). Although women
who were HPV-16 or HPV-18 positive at recruitment
Performance Characteristics of HPV Tests for were at higher risk of progression to CIN 2+ compared
Detection of CIN 2+ with women who were negative for those HPV types,
The tests for individual HPV types had high specificity most women who were HR HPV positive regressed to
(85%Y91%) but low sensitivity for the detection of normal cytology without treatment. In addition, some
progression to CIN 2+ (see Table 4). A combined HPV-16/ women who were HR HPV negative at recruitment
HPV-18 test showed a sensitivity of 58% and a specificity progressed to CIN 2+; in fact, almost one third of women
of 78%. The test for 14 HR HPV types had the highest who progressed to CIN 2+ were HR HPV negative, al-
sensitivity (68%) and lowest specificity (51%). Positive though our numbers are small. The properties of a single
(PPV) and negative (NPV) predictive values were similar HPV test around the time of diagnosis of CIN 1 were not
for all test options, with PPV ranging between 16% and sufficient to recommend its use for postcolposcopy man-
29% and NPV ranging between 90% and 93%. In the agement of CIN 1.
sensitivity analysis (restricted to the 109 women who had A particular strength of this study is that it included
either attended for the exit examination and/or who had an exit colposcopic examination to capture any disease
had CIN 2+ detected during follow-up) for each test not previously identified by cytology alone. Thirteen
option, sensitivity was unchanged, specificity was similar cases of CIN 2 were detected during follow-up and
to the primary analysis, and PPV was slightly higher at 7 cases at the exit colposcopy. Only 1 of the 8 cases of
the expense of lower NPV. CIN 3 was not detected until the exit colposcopy
examination.
The low rate of progression to CIN 2+ (12% at
DISCUSSION
3 years and 6% at 2 years) from our study is similar to
Our principal finding is that women with low-grade the results published from the ALTS group (12%) [7, 8],
cytological changes and histologically confirmed CIN 1 although the follow-up period was shorter, 24 months in
ALTS compared with 36 months in TOMBOLA. This
TABLE 3. Incidence Rates of CIN 2+ and Unadjusted
Relative Risks by HPV Infection, Age, and Smoking Status reflects the time within which most women with CIN 2+
are identified. There could have been various factors
Person years Incidence rate per Relative risk that could have contributed to the lower percentage of
Characteristic n at risk 100 person years (95% CI)
women developing CIN 2+ in our study group, including
HR HPV infection a larger proportion of high-grade CIN cases detected at
Negative 6 191.9 3.1 1 (reference)
Positive 13 202.1 6.4 2.06 (0.78Y.41) the initial colposcopy in TOMBOLA. We are aware of
Missing 2 one randomized controlled trial of alternative manage-
HPV-16 infection
Negative 13 328.9 4.0 1 (reference)
ment policies for women with biopsy-proven CIN 1.
Positive 6 65.1 9.2 2.33 (0.89Y6.14) This compared immediate treatment with conserva-
Missing 2
HPV-18 infection
tive colposcopy follow-up among 415 women across
Negative 14 352.5 4.0 1 (reference) 8 Canadian and 2 Brazilian colposcopy clinics [11]. The
Positive 5 41.4 12.1 3.04 (1.09Y8.44) rates of progression to CIN 2+ in each trial arm were
Missing 2
HPV-16 and/or not significantly different during 18 months of follow-
HPV-18 infection up (1.7% in the immediate treatment arm, 4.4% in the
Negative 8 292.8 2.7 1 (reference)
Positive 11 101.1 10.9 3.98 (1.60Y9.90) colposcopic follow-up arm) [11]. The rate of progres-
Missing 2 sion observed in the colposcopy arm of this study was
Age, y
20Y29 12 215.5 5.6 1 (reference)
lower than we observed, in part a function of the length
30Y39 7 108.0 6.5 1.16 (0.46Y2.96) of follow-up and also perhaps because of a difference in
40Y59 2 112.1 1.8 0.32 (0.07Y1.43)
Smoking status
underlying HPV prevalence.
Never smoker 10 190.6 5.2 1 (reference) We considered the effect of sociodemographic factors.
Ex-smoker 2 53.3 3.8 0.72 (0.16Y3.27) The majority of women were younger than 40 years
Current smokers 9 189.0 4.8 0.91 (0.37Y2.23)
(median age = 29 years). This reflects the transient nature
CIN indicates cervical intraepithelial neoplasia; HR, high risk; HPV, human papillomavirus. of most CIN 1 lesions, often related to HPV infection

Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
 Postcolposcopy Management of CIN 1 & 207

Table 4. Properties of HPV Tests in Predicting Progression to CIN 2+ by 3 Years of Follow-up

Sensitivity Specificity PPV NPV

(95% CI) (95% CI) (95% CI) (95% CI)

HR HPV test 68 (43.4Y87.4) 51 (42.0Y59.4) 16 (8.9Y26.2) 92 (83.3Y97.0)

HPV-16 test 32 (12.6Y56.6) 85 (78.2Y90.8) 23 (9.0Y43.6) 90 (83.4Y94.5)
HPV-18 test 26 (9.1Y51.2) 91 (85.1Y95.4) 29 (10.3Y56.0) 90 (83.6Y94.3)
Combined HPV-16 and 18 testa 58 (33.5Y79.7) 78 (70.0Y84.6) 27 (14.2Y42.9) 93 (86.6Y96.9)

a
A positive test result is defined as positive for HPV-16 and/or HPV-18. A negative test result is defined as negative for both HPV-16 and HPV-18.

whose prevalence is highest in younger women with a recall, similar to the UK Sentinel site study [7, 14]. The
high rate of subsequent regression. In the ALTS, smokers protocol for the sentinel sites study advocated cytology
had a 2-fold increased in progression to CIN 3 compared with or without colposcopy at 12 months for women
with women who were nonsmokers [12]. We did not find with CIN 1 who initially tested positive for HPV [14].
any association between smoking and risk of CIN 2+, and Based on the regression rates and the median time to
our numbers were insufficient to examine the risk of CIN progression (25 months) from our study, we would rec-
3 specifically. ommend conservative management with the first follow-
The only factors significantly associated with pro- up test at 24 months.
gression to CIN 2+ in our study were testing positive for (i)
HPV-18 infection, which increased the risk 3-fold, and (ii) Limitations
HPV-16 and/or HPV-18 infection, which increased the
Although the number of women included in this study
risk 4-fold. It is interesting to note that approximately
was small, the population basis and pragmatic nature of
half of the women with CIN 1 were HR HPV positive.
the TOMBOLA trial suggest that the results are likely
This is in contrast to the small percentage of women
to be generalizable, at least across the NHS Cervical
positive for type-specific HPV-16 (17%) and HPV-18
Screening Programmes. We have deliberately not un-
(11%). In the ALTS, women who tested positive for HPV-
dertaken post hoc power calculations because this
16 at the same time as they had the initial smear for
would not assist in the interpretation of our findings. We
atypical squamous cells of undetermined significance or
only included CIN 1 associated with low-grade cytology.
low-grade squamous intraepithelial lesion had a 5-fold
CIN 1 associated with high-grade cytology may reflect
increase in progression to CIN 3 or greater compared with
undetected high-grade CIN. It is possible that risk of
women who were not HPV-16 positive after 2 years of
progression would be greater in this group and HR HPV
follow-up [13].
testing may be of greater value in this context. More-
Despite the association between HPV-18 and HPV-16
over, we investigated the properties of a single HPV test
and/or HPV-18 and progression to CIN 2+, a single
at the time of trial recruitment (approximately 8 weeks,
HPV test around the time of detection of CIN 1 was not
on average, after the index smear that made the women
sufficient to recommend its use in clinical practice to de-
eligible to take part and 8 weeks before the biopsy, which
termine postcolposcopy management. The HPV tests as
confirmed presence of CIN 1). A follow-up HPV test after
used in this study lacked sensitivity and had low PPVs.
a histological diagnosis of CIN 1 may be more useful, but
Moreover, 6 of the women who developed CIN 2+ did not
we were not able to investigate this.
test positive for the 14 HR HPV types. In contrast, Elit
There were few defaulters in our study (10%), and this
et al. [11] showed that disease progression was identified
could be attributed to the fact that women had already
only in women who were positive for oncogenic HPV
agreed to participate in the TOMBOLA trial and may
types by Hybrid Capture II at baseline. This may be re-
therefore be more willing to participate in follow-up
lated to the shorter follow-up period.
compared with the wider colposcopy population.
The authors of the ALTS recommended a single HPV
test at 12 months as a reasonable follow-up for women
with CIN 1 or less [7]. This management strategy would Implications for Practice
improve sensitivity (92%) of an HPV test for detection of Our findings suggest that negative HPV test results in
CIN 2+ and lowered the colposcopy referral rates, po- women with CIN 1 should not be used to classify them
tentially allowing a third of women to return to routine as low risk and suitable for return to routine follow-up.

Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
208 & GURUMURTHY ET AL.
They are at lower risk compared with women who are
HPV positive but not at no risk. Although HPV-16/
HPV-18 positivity has an increased relative risk for high-
grade CIN being detected within 3 years of follow-up,
many will regress, so increased intervention does not
benefit this group either. This also implies that whether
CIN 1 is detected in systems where referral to colposcopy
depends on HPV cotesting and/or triage or neither, the
recommendation for postcolposcopy management does
not change.
CONCLUSIONS
Women with CIN 1 have a low rate of progression to
high-grade disease during 3 years. A single HPV DNA
test, around the time of the CIN 1 diagnosis, lacks
sensitivity and specificity and hence is not sufficient for
determining management. In policy circles, the value of
HPV testing in follow-up of women with CIN 1 may
have been overestimated. As the median time to pro-
gression was 25 months, conservative management for
women with CIN 1 could recommend next repeat cy-
tology at 2 years without intervening cytology or col-
poscopy review.
Acknowledgments
The authors are grateful for the cooperation and assistance
that they received from NHS staff in the coordinating centers
and clinical sites. They also thank the women who participated
in TOMBOLA.
The TOMBOLA Group is composed of the following:
Grant holders:
From the University of Aberdeen and NHS Grampian, Aber-
deen, Scotland: Maggie Cruickshank, Graeme Murray, David
Parkin, Louise Smart, Eric Walker, Norman Waugh (Principal
Investigator 2004Y2008);
From the University of Nottingham and Nottingham NHS,
Nottingham, England: Mark Avis, Claire Chilvers, Katherine
Fielding, Rob Hammond, David Jenkins, Jane Johnson, Keith
Neal, Ian Russell, Rashmi Seth, Dave Whynes;
From the University of Dundee and NHS Tayside, Dundee,
Tayside: Ian Duncan, Alistair Robertson (deceased);
From the University of Ottawa, Ottawa, Canada: Julian
Little (Principal Investigator 1999Y2004);
From the National Cancer Registry, Cork, Ireland: Linda
Sharp;
From the Bangor University, Bangor, Wales: Ian Russell;
From the University of Hull, Hull, England: Leslie Walker
Staff in clinical sites and coordinating centers
Grampian: Breda Anthony, Sarah Bell, Adrienne Bowie, Katrina
Brown (deceased), Joe Brown, Kheng Chew, Claire Cochran,
Seonaidh Cotton, Jeannie Dean, Kate Dunn, Jane Edwards,
David Evans, Julie Fenty, Al Finlayson, Marie Gallagher, Nicola
Gray, Maureen Heddle, Alison Innes, Debbie Jobson, Mandy
Copyright © 2014 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
Keillor, Jayne MacGregor, Sheona Mackenzie, Amanda Mackie,
Gladys McPherson, Ike Okorocha, Morag Reilly, Joan Rodgers,
Alison Thornton, Rachel Yeats;
Tayside: Lindyanne Alexander, Lindsey Buchanan, Susan
Henderson, Tine Iterbeke, Susanneke Lucas, Gillian Manderson,
Sheila Nicol, Gael Reid, Carol Robinson, Trish Sandilands;
Nottingham: Marg Adrian, Ahmed Al-Sahab, Elaine Bentley,
Hazel Brook, Claire Bushby, Rita Cannon, Brenda Cooper,
Ruth Dowell, Mark Dunderdale, Dr Gabrawi, Li Guo, Lisa
Heideman, Steve Jones, Salli Lawson, Zoë Philips, Christopher
Platt, Shakuntala Prabhakaran, John Rippin, Rose Thompson,
Elizabeth Williams, Claire Woolley;
Statistical analysis: Seonaidh Cotton, Kirsten Harrild, John
Norrie, Linda Sharp;
External Trial Steering Committee: Nicholas Day (chair,
1999Y2004), Theresa Marteau (chair, 2004 to present), Mahesh
Parmar, Julietta Patnick and Ciaran Woodman;
External Data Monitoring and Ethics Committee: Doug Altman
(chair), Sue Moss, Michael Wells.
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