Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial

Julian Little, Linda Sharp, Seonaidh Cotton, Maggie Cruickshank, Ian Duncan, Kirsten Harrild, David Jenkins, Louise Smart, Norman Waugh, Claire Cochran, Nicola Gray, Rob Hammond, Keith Neal, Alison J Thornton, Claire Woolley, The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group

Research output: Contribution to journalArticle

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Abstract

Objectives To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests.

Design Multicentre individually randomised controlled trial.

Setting NHS cervical screening programmes in Grampian, Tayside, and Nottingham.

Participants 4439 women, aged 20-59, with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.

Interventions Cytological screening every six months in primary care (n=2223) or referral for colposcopy and related interventions (n=2216). All women were followed for three years, concluding with an exit appointment at which colposcopic examination was undertaken. Colposcopists assessing outcome at this appointment were blinded to randomisation.

Main outcome measures Primary end point: cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease. Other end points: cervical intraepithelial neoplasia grade III or worse, clinically significant anxiety and depression, other self reported after effects, and rates of non-attendance. Analysis was by intention to treat; all those randomised were included.

Results The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm (relative risk 1.37, 95% confidence interval 1.19 to 1.57). This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease, but the incidence was still higher in the colposcopy arm (relative risk 1.26, 1.04 to 1.53). Among women randomised to immediate colposcopy, 79% (74.9% to 82.5%) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy, while among women randomised to cytological surveillance, 77% (72.1% to 81.2%) of cases were detected by surveillance cytology and related interventions. Similar proportions of women were anxious or depressed in the two arms. A higher proportion of women in the colposcopy arm reported after effects, and these were of longer duration and more severe. Non-attendance was low in both arms.

Conclusion The more marked difference between the arms in the occurrence of cervical intraepithelial neoplasia grade II or worse than in the occurrence of grade III or worse can probably be accounted for by the spontaneous regression of some cases of grade II neoplasia. Compared with cytological surveillance, a policy of immediate colposcopy detects more cervical intraepithelial neoplasia grade II or worse, and some more grade III or worse, but might lead to overtreatment. Such a policy is associated with a higher rate of reported after effects, which are more severe and of longer duration than those associated with cytological surveillance.

Original languageEnglish
Article numberb2546
Number of pages11
JournalBritish Medical Journal
Volume339
DOIs
Publication statusPublished - 28 Jul 2009

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Colposcopy
Cervical Intraepithelial Neoplasia
Referral and Consultation
Randomized Controlled Trials
Cell Biology
Primary Health Care
Incidence
Appointments and Schedules
Intention to Treat Analysis
Random Allocation
Anxiety
Outcome Assessment (Health Care)
Confidence Intervals
Depression

Keywords

  • adult
  • anxiety
  • cervical intraepithelial neoplasia
  • colposcopy
  • depression
  • female
  • follow-up studies
  • humans
  • incidence
  • mass screening
  • middle aged
  • quality assurance, health care
  • referral and consultation
  • uterine cervical dysplasia
  • uterine cervical neoplasms
  • young adult
  • squamous intraepithelial lesions
  • metaanalysis
  • participation
  • mild
  • smears
  • cancer
  • follow-up
  • cell carcinoma
  • human-papillomavirus
  • undetermined significance

Cite this

Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities : multicentre randomised controlled trial. / Little, Julian; Sharp, Linda; Cotton, Seonaidh; Cruickshank, Maggie; Duncan, Ian; Harrild, Kirsten; Jenkins, David; Smart, Louise; Waugh, Norman; Cochran, Claire; Gray, Nicola; Hammond, Rob; Neal, Keith; Thornton, Alison J; Woolley, Claire; The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group.

In: British Medical Journal, Vol. 339, b2546, 28.07.2009.

Research output: Contribution to journalArticle

Little, J, Sharp, L, Cotton, S, Cruickshank, M, Duncan, I, Harrild, K, Jenkins, D, Smart, L, Waugh, N, Cochran, C, Gray, N, Hammond, R, Neal, K, Thornton, AJ, Woolley, C & The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group 2009, 'Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial' British Medical Journal, vol. 339, b2546. https://doi.org/10.1136/bmj.b2546
Little, Julian ; Sharp, Linda ; Cotton, Seonaidh ; Cruickshank, Maggie ; Duncan, Ian ; Harrild, Kirsten ; Jenkins, David ; Smart, Louise ; Waugh, Norman ; Cochran, Claire ; Gray, Nicola ; Hammond, Rob ; Neal, Keith ; Thornton, Alison J ; Woolley, Claire ; The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group. / Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities : multicentre randomised controlled trial. In: British Medical Journal. 2009 ; Vol. 339.
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abstract = "Objectives To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests.Design Multicentre individually randomised controlled trial.Setting NHS cervical screening programmes in Grampian, Tayside, and Nottingham.Participants 4439 women, aged 20-59, with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.Interventions Cytological screening every six months in primary care (n=2223) or referral for colposcopy and related interventions (n=2216). All women were followed for three years, concluding with an exit appointment at which colposcopic examination was undertaken. Colposcopists assessing outcome at this appointment were blinded to randomisation.Main outcome measures Primary end point: cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease. Other end points: cervical intraepithelial neoplasia grade III or worse, clinically significant anxiety and depression, other self reported after effects, and rates of non-attendance. Analysis was by intention to treat; all those randomised were included.Results The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm (relative risk 1.37, 95{\%} confidence interval 1.19 to 1.57). This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease, but the incidence was still higher in the colposcopy arm (relative risk 1.26, 1.04 to 1.53). Among women randomised to immediate colposcopy, 79{\%} (74.9{\%} to 82.5{\%}) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy, while among women randomised to cytological surveillance, 77{\%} (72.1{\%} to 81.2{\%}) of cases were detected by surveillance cytology and related interventions. Similar proportions of women were anxious or depressed in the two arms. A higher proportion of women in the colposcopy arm reported after effects, and these were of longer duration and more severe. Non-attendance was low in both arms.Conclusion The more marked difference between the arms in the occurrence of cervical intraepithelial neoplasia grade II or worse than in the occurrence of grade III or worse can probably be accounted for by the spontaneous regression of some cases of grade II neoplasia. Compared with cytological surveillance, a policy of immediate colposcopy detects more cervical intraepithelial neoplasia grade II or worse, and some more grade III or worse, but might lead to overtreatment. Such a policy is associated with a higher rate of reported after effects, which are more severe and of longer duration than those associated with cytological surveillance.",
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author = "Julian Little and Linda Sharp and Seonaidh Cotton and Maggie Cruickshank and Ian Duncan and Kirsten Harrild and David Jenkins and Louise Smart and Norman Waugh and Claire Cochran and Nicola Gray and Rob Hammond and Keith Neal and Thornton, {Alison J} and Claire Woolley and {The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group}",
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TY - JOUR

T1 - Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities

T2 - multicentre randomised controlled trial

AU - Little, Julian

AU - Sharp, Linda

AU - Cotton, Seonaidh

AU - Cruickshank, Maggie

AU - Duncan, Ian

AU - Harrild, Kirsten

AU - Jenkins, David

AU - Smart, Louise

AU - Waugh, Norman

AU - Cochran, Claire

AU - Gray, Nicola

AU - Hammond, Rob

AU - Neal, Keith

AU - Thornton, Alison J

AU - Woolley, Claire

AU - The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group

PY - 2009/7/28

Y1 - 2009/7/28

N2 - Objectives To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests.Design Multicentre individually randomised controlled trial.Setting NHS cervical screening programmes in Grampian, Tayside, and Nottingham.Participants 4439 women, aged 20-59, with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.Interventions Cytological screening every six months in primary care (n=2223) or referral for colposcopy and related interventions (n=2216). All women were followed for three years, concluding with an exit appointment at which colposcopic examination was undertaken. Colposcopists assessing outcome at this appointment were blinded to randomisation.Main outcome measures Primary end point: cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease. Other end points: cervical intraepithelial neoplasia grade III or worse, clinically significant anxiety and depression, other self reported after effects, and rates of non-attendance. Analysis was by intention to treat; all those randomised were included.Results The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm (relative risk 1.37, 95% confidence interval 1.19 to 1.57). This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease, but the incidence was still higher in the colposcopy arm (relative risk 1.26, 1.04 to 1.53). Among women randomised to immediate colposcopy, 79% (74.9% to 82.5%) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy, while among women randomised to cytological surveillance, 77% (72.1% to 81.2%) of cases were detected by surveillance cytology and related interventions. Similar proportions of women were anxious or depressed in the two arms. A higher proportion of women in the colposcopy arm reported after effects, and these were of longer duration and more severe. Non-attendance was low in both arms.Conclusion The more marked difference between the arms in the occurrence of cervical intraepithelial neoplasia grade II or worse than in the occurrence of grade III or worse can probably be accounted for by the spontaneous regression of some cases of grade II neoplasia. Compared with cytological surveillance, a policy of immediate colposcopy detects more cervical intraepithelial neoplasia grade II or worse, and some more grade III or worse, but might lead to overtreatment. Such a policy is associated with a higher rate of reported after effects, which are more severe and of longer duration than those associated with cytological surveillance.

AB - Objectives To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests.Design Multicentre individually randomised controlled trial.Setting NHS cervical screening programmes in Grampian, Tayside, and Nottingham.Participants 4439 women, aged 20-59, with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.Interventions Cytological screening every six months in primary care (n=2223) or referral for colposcopy and related interventions (n=2216). All women were followed for three years, concluding with an exit appointment at which colposcopic examination was undertaken. Colposcopists assessing outcome at this appointment were blinded to randomisation.Main outcome measures Primary end point: cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease. Other end points: cervical intraepithelial neoplasia grade III or worse, clinically significant anxiety and depression, other self reported after effects, and rates of non-attendance. Analysis was by intention to treat; all those randomised were included.Results The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm (relative risk 1.37, 95% confidence interval 1.19 to 1.57). This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease, but the incidence was still higher in the colposcopy arm (relative risk 1.26, 1.04 to 1.53). Among women randomised to immediate colposcopy, 79% (74.9% to 82.5%) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy, while among women randomised to cytological surveillance, 77% (72.1% to 81.2%) of cases were detected by surveillance cytology and related interventions. Similar proportions of women were anxious or depressed in the two arms. A higher proportion of women in the colposcopy arm reported after effects, and these were of longer duration and more severe. Non-attendance was low in both arms.Conclusion The more marked difference between the arms in the occurrence of cervical intraepithelial neoplasia grade II or worse than in the occurrence of grade III or worse can probably be accounted for by the spontaneous regression of some cases of grade II neoplasia. Compared with cytological surveillance, a policy of immediate colposcopy detects more cervical intraepithelial neoplasia grade II or worse, and some more grade III or worse, but might lead to overtreatment. Such a policy is associated with a higher rate of reported after effects, which are more severe and of longer duration than those associated with cytological surveillance.

KW - adult

KW - anxiety

KW - cervical intraepithelial neoplasia

KW - colposcopy

KW - depression

KW - female

KW - follow-up studies

KW - humans

KW - incidence

KW - mass screening

KW - middle aged

KW - quality assurance, health care

KW - referral and consultation

KW - uterine cervical dysplasia

KW - uterine cervical neoplasms

KW - young adult

KW - squamous intraepithelial lesions

KW - metaanalysis

KW - participation

KW - mild

KW - smears

KW - cancer

KW - follow-up

KW - cell carcinoma

KW - human-papillomavirus

KW - undetermined significance

U2 - 10.1136/bmj.b2546

DO - 10.1136/bmj.b2546

M3 - Article

VL - 339

JO - BMJ

JF - BMJ

SN - 0959-8146

M1 - b2546

ER -