Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy

multicentre randomised controlled trial

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

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Objectives To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy.

Design Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes.

Setting Grampian, Tayside, and Nottingham.

Participants 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.

Interventions Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy.

Main outcome measures Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision.

Results 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge.

Conclusion A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended.

Trial Registration ISRCTN 34841617.
Original languageEnglish
Article numberb2548
Number of pages12
JournalBritish Medical Journal
Volume339
DOIs
Publication statusPublished - 28 Jul 2009

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Colposcopy
Cervical Intraepithelial Neoplasia
Cell Biology
Randomized Controlled Trials
Biopsy
Anxiety
Depression
Therapeutics
Incidence
Ambulatory Care
Outcome Assessment (Health Care)
Confidence Intervals
Hemorrhage
Pain

Keywords

  • squamous intraepithelial lesions
  • directed punch biopsy
  • treatment too soon
  • see-and-treat
  • transformation zone
  • follow-up
  • long-term
  • neoplasia
  • diagnosis
  • metaanalysis

Cite this

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial. / Sharp, Linda (Corresponding Author); Cruickshank, Maggie; Little, Julian; Cotton, Seonaidh; Harrild, Kirsten; Cochran, Claire; Duncan, Ian; Gray, Nicola; Hammond, Rob; Smart, Louise; Thornton, Alison; Waugh, Norman; Woolley, Claire; The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group.

In: British Medical Journal, Vol. 339, b2548, 28.07.2009.

Research output: Contribution to journalArticle

Sharp, L, Cruickshank, M, Little, J, Cotton, S, Harrild, K, Cochran, C, Duncan, I, Gray, N, Hammond, R, Smart, L, Thornton, A, Waugh, N, Woolley, C & The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group 2009, 'Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial', British Medical Journal, vol. 339, b2548. https://doi.org/10.1136/bmj.b2548
Sharp, Linda ; Cruickshank, Maggie ; Little, Julian ; Cotton, Seonaidh ; Harrild, Kirsten ; Cochran, Claire ; Duncan, Ian ; Gray, Nicola ; Hammond, Rob ; Smart, Louise ; Thornton, Alison ; Waugh, Norman ; Woolley, Claire ; The TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group. / Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial. In: British Medical Journal. 2009 ; Vol. 339.
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abstract = "Objectives To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy.Design Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes.Setting Grampian, Tayside, and Nottingham.Participants 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.Interventions Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy.Main outcome measures Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision.Results 879 women (44{\%}) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60{\%}) in the biopsy and selective recall group; 501 (51{\%}) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16{\%}) required a second clinic visit for treatment. Specimens from almost 60{\%} (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31{\%}; n=156) or showed cervical intraepithelial neoplasia grade I (28{\%}; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22{\%} (n=216) in the biopsy and recall arm and 23{\%} (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95{\%} confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge.Conclusion A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended.Trial Registration ISRCTN 34841617.",
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author = "Linda Sharp and Maggie Cruickshank and Julian Little and Seonaidh Cotton and Kirsten Harrild and Claire Cochran and Ian Duncan and Nicola Gray and Rob Hammond and Louise Smart and Alison Thornton and Norman Waugh 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 - Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy

T2 - multicentre randomised controlled trial

AU - Sharp, Linda

AU - Cruickshank, Maggie

AU - Little, Julian

AU - Cotton, Seonaidh

AU - Harrild, Kirsten

AU - Cochran, Claire

AU - Duncan, Ian

AU - Gray, Nicola

AU - Hammond, Rob

AU - Smart, Louise

AU - Thornton, Alison

AU - Waugh, Norman

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 compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy.Design Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes.Setting Grampian, Tayside, and Nottingham.Participants 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.Interventions Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy.Main outcome measures Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision.Results 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge.Conclusion A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended.Trial Registration ISRCTN 34841617.

AB - Objectives To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy.Design Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes.Setting Grampian, Tayside, and Nottingham.Participants 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.Interventions Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy.Main outcome measures Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision.Results 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge.Conclusion A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended.Trial Registration ISRCTN 34841617.

KW - squamous intraepithelial lesions

KW - directed punch biopsy

KW - treatment too soon

KW - see-and-treat

KW - transformation zone

KW - follow-up

KW - long-term

KW - neoplasia

KW - diagnosis

KW - metaanalysis

U2 - 10.1136/bmj.b2548

DO - 10.1136/bmj.b2548

M3 - Article

VL - 339

JO - BMJ

JF - BMJ

SN - 0959-8146

M1 - b2548

ER -