Proposed New Guidelines for the Management of Women with Abnormal Cervical Smears DRAFT FOR COMMENT

Transcription

1 Proposed New Guidelines for the Management of Women with Abnormal Cervical Smears DRAFT FOR COMMENT National Cervical Screening Programme National Screening Unit Ministry of Health October 2006

2 Table of Contents Table of Contents Introduction Summary Questions and comment Proposed New Guideline Management of women with previously normal cervical smears Management of women with unsatisfactory cervical smears Management of women with low-grade squamous abnormalities Colposcopic assessment of women with LSIL / ASC-US Management of women with histologically confirmed LSIL Management of women with high-grade squamous abnormalities Management of women with histologically confirmed HSIL Management of women previously treated for HSIL Management of women with cervical glandular abnormalities Colposcopic assessment and treatment of women with glandular abnormalities Management of women in special clinical circumstances Summary of indications and cases for cytological review Tables...18 Table 1: Management of women with low grade squamous abnormalities...18 Table 2: Management of women with high grade abnormalities...19 Table 3: Management of women with glandular abnormalities...20 Appendix A: Guideline Development Team...21 Appendix B: Guideline Development Process...22 Appendix C: AGREE Tool...25 Appendix D: Rigor Score...26 Appendix E: New Zealand Grading System...27 Appendix F: NCSP Register Data Analysis...28 Abbreviations...34 Glossary...35 References...38 International Guidelines...38 Low grade squamous abnormalities (LSIL / ASC-US)...38 High grade squamous abnormalities (HSIL / ASC-H)...41 Glandular abnormalities (AGC / AIS)...43 Unsatisfactory Cervical Smears...44 Women in special clinical circumstances...45 Human Papilloma Virus (HPV)

3 1. Introduction This document summarises the recommendations and draft guidelines developed by the 2005 Guidelines Development Team. The National Screening Unit (NSU) of the Ministry of Health in association with this multidisciplinary team has reviewed the 1999 Guidelines for the management of women with abnormal cervical smears and is proposing these draft new guidelines for wider health sector review and comment. The Guidelines Development Team (GDT) was established in 2005 to review and update the current guidelines published in The New Zealand Guidelines Group (NZGG) were contracted to assist and support NSU representatives and the multidisciplinary GDT, who consisted of one general practitioner, two epidemiologists, one consumer, two gynaecological oncologists, two pathologists and three experienced colposcopists, one of whom represented the rural sector. The GDT members are listed in Appendix A. The development of these proposed new guidelines is in accordance with an evidence based methodology, including an extensive review of the literature, as detailed in Appendices B to E. The recently published Australian guidelines, Guidelines for the management of asymptomatic women with screen detected abnormalities, (National Health and Research Council (NHMRC) 2005) were used as a major resource and its recommendations considered in the New Zealand context. Approval to use the Australian Guidelines was received from the Department of Health and Aging, Commonwealth of Australia, in June The Australian guidelines are referenced throughout this document. 2. Summary These proposed new Guidelines for the Management of Women with Abnormal Cervical Smears are presented in summary table format for review and comment. Three table flow charts summarising management are also included for review and comment. Any comments and feedback will be reviewed and assessed by the GDT before the final guidelines document is completed, with full discussion of the evidence, for publication in Implementation of the new guidelines is anticipated to be from 1 July 2007 following the implementation of changes to the National Cervical Screening Programme (NCSP) Register. The 1999 Guidelines for the Management of Women with Abnormal Cervical Smears was used as a basis for looking at new evidence that had become available since its publication. The NSU and the GDT acknowledge the work of the 1998 Working Party chaired by Mr Ron Jones, and the proposed new guidelines have built upon and extended many of the 1999 recommendations. The NZGG critically appraised five of the most evidence based international guidelines on management of women with abnormal smears, using the AGREE Tool in Appendix C. The five guidelines used were from Australia, United Kingdom, Ontario, the American Society of Colposcopy and Cervical Pathology (ASCCP), and 3

4 the Institute of Clinical Systems Improvement (ICSI). These international guideline recommendations were also compared to the 1999 New Zealand guideline. Clinical questions were developed for use with identified relevant studies that were appraised for quality. Evidence tables were prepared for each of the clinical questions along with summaries and considered judgement forms. The GDT then developed recommendations that are the basis of this proposed new guideline document. The most significant proposed changes for the new guidelines include: 1. Options for changes to the follow up time interval for women with low grade cytological abnormalities of both atypical squamous cells of undetermined significance (ASC-US) and low grade squamous intraepithelial lesions (LSIL). Ongoing management options are proposed for consideration depending on the clinical situation. 2. The potential use of HPV testing. These recommendations are dependant on the findings of an economic evaluation of the costs and benefits for women and the health sector and this work is currently being undertaken by the NCSP. HPV testing is being investigated and / or proposed for the following scenarios: o Post treatment follow up of women with HSIL (test of cure) to enable women to return to three yearly screening instead of annual screening until the age of 70 years. o Triage of women with ASC-US to reduce the need for colposcopy referral The management of women with normal cervical smears is recommended in section 4.1, followed by proposed new guidelines for: Management of women with unsatisfactory cervical smears Management of women with low-grade squamous abnormalities Colposcopic assessment of women with LSIL / ASC-US Management of women with histologically confirmed LSIL Management of women with high-grade squamous abnormalities Management of women with histologically confirmed high grade squamous intraepithelial lesions (HSIL) Management of women previously treated for HSIL Management of women with cervical glandular abnormalities Colposcopic assessment and treatment of women with glandular abnormalities Management of women in special clinical circumstances Summary of indications and cases for cytological review. 4

5 3. Questions and comment Your comment is invited on these proposed new guidelines. This feedback will assist in the development of the final published guideline. Any questions can be addressed to: Dr Hazel Lewis, Clinical Leader, NCSP Phone (04) Please send comments to: Diane Casey by: Monday 11 December 2006 via , fax or in writing to: Diane Casey, Senior Analyst, National Screening Unit. Private Bag Wellesley Street Auckland Phone (09) Fax (09) We look forward to receiving your comments 5

6 4. Proposed New Guideline These proposed new Guidelines for the Management of Women with Abnormal Cervical Smears are presented in summary table format with columns for evidence grading as per Appendix E, and 1999 guideline changes to enable review and comparison. The first table (4.1) covers management of women with previously normal cervical smears as a baseline, followed by the proposed new guidelines for the management of women with: unsatisfactory cervical smears low-grade squamous abnormalities high-grade squamous abnormalities glandular abnormalities special clinical circumstances 4.1 Management of women with previously normal cervical smears CERVICAL SMEAR REPORT Negative for squamous or glandular epithelial lesion or malignancy Negative for squamous or glandular epithelial lesion or malignancy, but this is the first smear, or more than 5 years has elapsed since previous smear 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES Recall in 3 years for cervical smear unless falls into category below. (IARC 2005, WHO 2006) Recall in 12 months for cervical smear. (IARC 2005, WHO 2006) 4.2 Management of women with unsatisfactory cervical smears Unsatisfactory Repeat cervical smear at 3 months. Referral for colposcopy should be considered after three unsatisfactory smear reports. Note: LBC Policy Statement (2006) There may be situations where liquid based cytology (LBC) offers some advantage over conventional smears, such as women with: excessive cervical mucus, discharge or blood recurrent inflammatory smears recurrent unsatisfactory smears The introduction of ancillary tests, for example HPV, and automated screening devices is evolving rapidly. These developments together with long-term workforce issues may become deciding factors in the future for the wider use of LBC. LBC expert working group (NCSP Policy Statement 2006) Change 6

7 4.3 Management of women with low-grade squamous abnormalities CERVICAL SMEAR REPORT Index smear report of low grade squamous intraepithelial lesions (LSIL) or atypical squamous cells of undetermined significance (ASC-US) 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES Repeat cervical smear at 12 months unless the women falls into the category below. Note: An economic evaluation of HPV testing for ASC-US is being undertaken. This work will inform NCSP policy due for completion in mid (NCSP-R analysis, NHMRC 2005) Change Index smear report of LSIL / ASC-US in woman aged 30 years and over A woman aged 30 years and over with a history of abnormal smears in the preceding 3 years should be offered either immediate colposcopy or a repeat smear within 6 months. NHMRC 2005) Change Twelve month repeat smear report after index LSIL / ASC-US If the 12-month repeat smear is reported as showing high-grade changes (or atypical squamous cells cannot exclude high grade, ASC-H), the woman should be referred for colposcopic assessment. If the 12 month repeat smear is reported as LSIL / ASC-US the woman should be referred for colposcopic assessment. Change Note: Women with persistent low-grade abnormalities should receive colposcopy within 26 weeks of receipt of referral (OPQS Standard 602). (This standard may require review given the above proposed change to the recall interval following a first LSIL / ASCUS.) If the 12-month repeat smear is reported as negative, the woman should have a further repeat smear in 12 months (ie 24 months after the index smear). Change Fluctuating repeat smear reports with two LSIL / ASC-US smear reports within 3 years A woman with fluctuating repeat smear reports should be referred for colposcopy regardless of intervening negative smear reports. I.e. If a woman has had two LSIL/ASCUS reports (at least 12 months apart within a 3 year time frame), regardless of normal cytology reports, she should be referred for colposcopy. Change 7

8 4.4 Colposcopic assessment of women with LSIL / ASC-US COLPOSCOPIC ASSESSMENT Satisfactory and normal 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES The woman should be referred back to the smear taker for annual cytological surveillance until two (RANZCOG Change normal consecutive smear results are obtained when 2001, NHMRC she should resume routine (3 yearly) screening. 2005) Satisfactory with low grade lesion suspected or seen Target biopsy should be performed to confirm this diagnosis. A biopsy is recommended for any abnormality of transformation zone. (RANZCOG 2001, NHMRC 2005) Satisfactory with high grade lesion suspected or seen Unsatisfactory colposcopic assessment Targeted biopsy should be performed for histological confirmation before definitive therapy. 1. Cytology review is recommended. 2. Consider repeat cytology and / HPV test if woman aged over 30 years. 3. If abnormal cytology or positive HPV, repeat colposcopy is recommended. (RANZCOG 2001, NHMRC 2005) (Good practice point) (RANZCOG 2001, NHMRC 2005) Change 4. Further diagnostic procedures not indicated unless abnormality is persistent. Note: An economic evaluation of HPV testing is being undertaken. This work will inform NCSP policy due for completion in mid

9 4.5 Management of women with histologically confirmed LSIL HISTOLOGY REPORT 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES Histologically confirmed low grade squamous abnormalities Treatment is not recommended, as such lesions are considered to be an expression of a productive HPV infection. Change Repeat cytology at 12 and 24 months. If both smears are negative, it is recommended that the woman return to routine 3 yearly screening. Options 1. If either repeat smear shows ASC-US / LSIL then the woman should be referred back to colposcopy. OR 2. If either repeat smear shows ASC-US / LSIL, the woman should be advised to continue having annual smears until at least two are negative, at which time she can return to routine screening. OR 3. If either repeat smear shows ASC-H / HSIL the woman should be referred back to colposcopy as per management of women with high grade squamous abnormalities. In asymptomatic women and in the absence of colposcopic, cytologic or histologic suggestion of high grade disease, further diagnostic procedures such as cone biopsy or loop excision are not indicated. Note: An economic evaluation of HPV testing is being undertaken. This work will inform NCSP policy due for completion in mid (RANZCOG 2001, NHMRC 2005) (RANZCOG 2001, NHMRC 2005) (RANZCOG 2001, NHMRC 2005) 9

10 4.6 Management of women with high-grade squamous abnormalities CERVICAL SMEAR REPORT Index smear report of atypical squamous cells possible high grade (ASC-H) Index smear report of high grade squamous intraepithelial lesions (HSIL) 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES A woman with a smear report of possible high grade squamous lesion should be referred for colposcopic assessment and targeted biopsy where indicated. Note: Women with high-grade smear abnormalities should receive colposcopy within 4 weeks of receipt of referral (OPQS Standard 602). A woman with a smear report of HSIL should be referred to a gynaecologist for colposcopic assessment and targeted biopsy where indicated. Note: Women with high-grade smear abnormalities should receive colposcopy within four weeks of receipt of referral (OPQS Standard 602). Histological confirmation of abnormality is recommended prior to treatment and is required before ablative therapy or hysterectomy is undertaken. Index smear report of HSIL with normal colposcopy / negative histology Note: See and treat should only be considered if it is thought this may be the only opportunity to undertake treatment and: Circumstances are appropriate or immediate treatment is necessary. The colposcopic examination is consistent with the referral. The limits of the lesion are visible. The whole abnormality can be excised. There is no suspicion of invasion. There is an excisional specimen available for histological examination (OPQS Page 6.27). Cytology review is recommended for normal colposcopy. Multidisciplinary case review is recommended for cyto-histo correlation. (Good practice point) HPV testing in combination with cytology may allow a woman to return to three yearly screening if both are negative. Change Smear report of HSIL with suspected invasion Note: An economic evaluation of HPV testing is being undertaken. This work will inform NCSP policy due for completion in mid A woman with a smear report of HSIL with additional features suggestive of an invasive component should be seen by a gynaecological colposcopist or a gynaecologic oncologist within one week of receipt of referral. Smear report of squamous cell carcinoma (SCC) A woman with a smear report of SCC should be referred to a gynaecological colposcopist or gynaecological oncologist for urgent evaluation within one week of receipt of referral. 10

11 4.7 Management of women with histologically confirmed HSIL HISTOLOGY REPORT HSIL 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES A woman with a histological diagnosis of CIN2 or CIN3 should be treated in order to reduce the risk of developing invasive cervical carcinoma. Special circumstances see below 1. Women aged under 20 years 2. Fertility sparing treatments Grade A HSIL in women aged under 20 years The Guideline Development Team considered that in some circumstances there may be a role for the short term (6 12 months) observation of high-grade lesions that have been histologically confirmed (CIN2). Grade I Change It is strongly recommended that women under 20 years are not screened. Multidisciplinary review of histology and cytology is recommended (Good practice point) HSIL in women who wish to have children Local ablative or excisional treatments should destroy or remove abnormal tissue to a depth of at least 7mm. There is no clearly superior method of fertility sparing treatment of CIN 2 and 3. Grade A HSIL TREATMENT Ablative therapy Ablative therapy may be considered, provided: 1. The cervix has been assessed by an experienced colposcopist. 2. A targeted biopsy has confirmed the diagnosis. 3. There is no evidence of an invasive cancer on cytology, colposcopic assessment or biopsy. 4. There is no evidence of a glandular lesion on cytology or biopsy or colposcopy. 5. The entire lesion needs to be visualised. Cryotherapy for treatment of CIN 3 It is advisable that women with CIN 3 are not treated with cryotherapy. Loop electro-excisional procedure (LEEP), (LLETZ) Excess diathermy artifact should be avoided when using diathermy loops in order to allow comprehensive pathological examination, including margin status. 11

12 Cone Biopsy Cone biopsy may be necessary to treat women with high grade squamous lesions. Indications include: 1. Failure to visualise the upper limit of the cervical transformation zone in a woman with high grade squamous abnormality on her referral cervical smear (ie unsatisfactory colposcopy). Cone Biopsy (continued) 2. Suspicion of an early invasive cancer on cytology, biopsy or colposcopic assessment. 3. The suspected presence of an additional glandular abnormality (e.g. adenocarcinoma in situ) on cytology or biopsy (ie a mixed lesion). Careful attention should be paid to tailoring treatment to the individual woman, taking into account size, extent, situation and severity of the lesion. 4.8 Management of women previously treated for HSIL FOLLOW UP 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES Routine follow up A woman previously treated for HSIL should be examined colposcopically and have a smear taken six months after treatment. A repeat smear should then also be carried out at 12 months after treatment and annually thereafter until the age of 70 years. Change Any symptoms should be appropriately managed. HPV testing in combination with cytology may allow a woman to return to 3 yearly screening after treatment for HSIL. If a woman tests negative on cytology and HPV testing on two consecutive tests 12 months apart she can return to 3 yearly screening. The first HPV test should not be taken earlier than 12 months after treatment. Change Surveillance (long term follow up) post treatment for women with CIN2/3 Note: An economic evaluation of HPV testing is being undertaken. This work will inform NCSP policy due for completion in mid Continue annual cytology until aged 70 years. A woman already undergoing annual cytological review because of previously treated HSIL, may be offered HPV testing as described above. Once she has tested negative by both cytology and HPV on two consecutive occasions, she should be screened 3 yearly. (See note above re HPV testing) Change 12

13 4.9 Management of women with cervical glandular abnormalities CERVICAL SMEAR REPORT Smear report of adenocarcinoma 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES A woman with a smear report of adenocarcinoma of endometrial origin should be referred to a gynaecological colposcopist or to a gynaecological oncologist. A woman with a smear report of adenocarcinoma of either endocervical, extrauterine or unspecified origin should be referred to a gynaecological colposcopist or to a gynaecological oncologist. Smear report of endocervical adenocarcinoma in situ (AIS). A woman with a smear report of AIS should be referred to a gynaecological colposcopist or to a gynaecological oncologist. Note: Women who have evidence of clinical suspicion of invasive carcinoma, or a suspicion of invasive disease, receive colposcopy or a gynaecological assessment within one week of receipt of referral. (OPQS Standard 602). Smear report of atypical glandular or atypical endocervical cells of undetermined significance (AGUS) A woman with a smear report of atypical glandular or atypical endocervical cells should be referred to a gynaecological colposcopist or to a gynaecological oncologist. Note: There is a risk of cancer in this group. A second opinion should be considered. Change 13

14 4.10 Colposcopic assessment and treatment of women with glandular abnormalities ASSESSMENT / TREATMENT Assessment 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES Colposcopic assessment is mandatory in the presence of cervical cytology suggesting glandular abnormalities. Cone biopsy Cold knife cone biopsy should be considered the gold standard for the assessment of glandular abnormalities. Referral for women with adenocarcinoma on cone or punch biopsy Management of women with a smear report of AIS Management of women with a cone biopsy report of AIS Women found to have adenocarcinoma on cone or punch biopsy should be referred to a gynaecological oncologist or a gynaecological oncology unit for subsequent management. If invasive carcinoma is not identified at colposcopic assessment, a cone biopsy should be undertaken. Hysterectomy should not be undertaken without prior cone biopsy to exclude invasive carcinoma. The management of women diagnosed with AIS on cone biopsy will be dependant upon the age and fertility expectations of the woman and the status of the excision margins. NHMRC 2005) AIS treatment (with cone) follow up Hysterectomy should be discussed, and may be recommended for women who have completed childbearing because of the difficulties of reliable cytological follow up, a high recurrence rate and the reported multifocal nature of the disease. 1. Follow up colposcopy and cytology taken by endocervical brush 6 months after treatment. Change 2. Repeat cytology at 12 months then annual cytology. 3. Early follow up of symptoms is recommended. 4. If the cone biopsy has positive margins, on receipt of results, consideration should be given to further treatment. 14

15 4.11 Management of women in special clinical circumstances SPECIAL CIRCUMSTANCES Evaluation of an abnormal cervical smear result during pregnancy 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES Women who are pregnant with low-grade cytologic lesions should be managed in the same way as any woman with a low grade squamous abnormality, with a repeat smear after 12 months. Change Women with high-grade lesions should be referred for colposcopic evaluation. A second opinion should be considered. Colposcopy during pregnancy The aims of colposcopy in the pregnant woman are to exclude the presence of invasive cancer and to reassure the woman that her pregnancy will not be affected by an abnormal cervical smear result. Change Biopsy of the cervix in pregnancy is only indicated if invasion is suspected colposcopically. Treatment of a high grade lesion during pregnancy Definitive treatment of a high-grade lesion, with the exception of invasive cancer, may be safely deferred until after the pregnancy. Change Immunosupressed women An immunosuppressed woman with a screendetected abnormality should be referred for colposcopy, even for a low-grade lesion, as cytological surveillance alone may be inadequate. Grade A Assessment and treatment should be by a gynaecological colposcopist. The whole of the lower genital tract will need evaluation, as the same risk factors apply for cervical, vaginal, vulval and perianal lesions. Treatment of the cervix should be by excisional methods. Follow up after treatment should include colposcopy as well as cytology. Follow up should be annual and indefinite. Post menopausal women with normal endometrial cells Endometrial cells in women over 40 years can be a normal finding and is rarely associated with endometrial pathology, such as endometrial carcinoma. It is recommended that this finding be correlated with symptoms of uterine pathology e.g. abnormal bleeding. Grade A A symptomatic postmenopausal woman requires investigation regardless of her cervical smear results. Note: Atypical endometrial cells have high correlation with endometrial pathology. Urgent referral to a gynaecological colposcopist is recommended. Grade A (RANZCOG 2002, NHMRC 2005) 15

16 SPECIAL CIRCUMSTANCES Women exposed in utero to diethylstilboestrol (DES) 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES DES exposed women should be offered annual cytological screening and colposcopic examination of both the cervix and vagina. Screening should begin any time at the woman s request and continue indefinitely. A balanced perspective should be maintained. (Paul 2006) DES exposed women who have a screen detected abnormality should be managed in a specialist centre by a gynaecological colposcopist. Women with previous total hysterectomy Women who have undergone a total hysterectomy for documented benign reasons and have a normal smear history, are not recommended to require routine vaginal vault cytology. Women who have an unknown smear history should have baseline vaginal vault cytology. If this is normal, no further vaginal vault cytology is required. Women with previous sub total hysterectomy Women with histological evidence of CIN1 at any time in the past should have 3 yearly vaginal vault cytology until aged 70 years. Women who have had a sub total hysterectomy require routine screening as per the guidelines. Women with previous total hysterectomy for CIN 2 or 3 Guidelines for high grade abnormality shall apply Women with histological evidence of a high grade lesion at any time in the past should have annual vaginal vault smears until aged 70 years. Women with hysterectomy for genital malignancy HPV testing may be carried out at 12 months after treatment i.e. follow up with cytology and HPV testing annually until the woman has tested negative by both tests on two consecutive occasions. Note: An economic evaluation of HPV testing is being undertaken. This work will inform NCSP policy due for completion in mid These women should be under ongoing surveillance from a gynaecological oncologist. Therefore, they will be guided by this specialist about appropriate surveillance and care and will automatically no longer be the subject of these guidelines. Change Change 16

17 4.12 Summary of indications and cases for cytological review CASE REVIEW 2006 DRAFT GUIDELINE EVIDENCE 1999 GUIDELINES Cytology / case review Some cases may require cytology review or cytohisto correlation at multidisciplinary case review (Good Change meetings. practice point) Multidisciplinary case review is recommended in the following situations: HSIL in women aged under 20 years HSIL cytology and normal findings at colposcopic assessment. Abnormal glandular cytology and normal findings at colposcopic assessment. Persistent LSIL and normal findings at colposcopic assessment. Unsatisfactory colposcopic assessment of women with suggested high-grade disease. Note: For further information on cyto-histo correlations please refer to Standard 521, Page Chapter 5 Providing a Laboratory Service (OPQS). Three table flow charts follow on pages to summarise the proposed management of low grade, high grade and glandular abnormalities. 17

18 5. Tables Table 1: Management of women with low grade squamous abnormalities NEGATIVE INDEX SMEAR LSIL/ASCUS All Ages Repeat cytology 12/12 LSIL or ASCUS HSIL / ASC H If the woman is aged 30 years and over with a history of abnormal smears in the preceding 3 years, she should be offered immediate colposcopy or a repeat smear in 6 months HPV Testing: An economic evaluation of HPV testing is being undertaken. This work will inform NCSP policy due for completion in mid Repeat cytology 12/12 COLPOSCOPY NEGATIVE UNSATISFACTORY SATISFACTORY Routine Screening Review cytology lower genital tract examination NORMAL refer to Smear Taker for annual smears ABNORMAL target biopsy HSIL HISTOLOGY refer to management of high grade abnormalities LSIL Histology Options depending on clinical situation Cytology review is recommended. Consider repeat cytology. If atrophic consider course of vaginal oestrogen prior to repeat colposcopy. Observation with colposcopy and cytology / histology no later than 12 months. Repeat cytology 12/12 NEGATIVE Repeat cytology 12/12 NEGATIVE NEGATIVE Repeat cytology 12/12 NEGATIVE Repeat cytology 12/12 LSIL / ASCUS HSIL/ASC H refer to management of high grade abnormalities Routine 3 yearly Screening Routine 3 yearly Screening OPTIONS: 1) Colposcopy OR 2) Annual Cytology until at least 2 are negative. (RANZCOGS 2001) REFERENCES: NHMRC (2005). Screening to Prevent Cervical Cancer: Guidelines for the Management of Asymptomatic Women with Screen Detected Abnormalities. NHMRC, Canberra. Histologicaly confirmed low grade squamous abnormalities can be safely managed by repeat cytology at 12 and 24 months. (Pg. 48) Treatment of histologicaly confirmed low grade squamous lesions is not recommended, as such lesions are considered to be an expression of a productive HPV infection. (Pg.48) In asymptomatic women and in the absence of colposcopic, cytologic or histologic suggestion of high grade disease, further diagnostic procedures such as cone biopsy or loop excision are not indicated. RANZCOG (Royal Australian and New Zealand College of Obstetricians and Gynaecologists) (2001) RANZCOG Standards in Colposcopy and Treatment. Report of a RANZCOG and Austalian Society of Colposcopy and Cervical Pathology working party. 18

19 Table 2: Management of women with high grade abnormalities INDEX SMEAR HSIL or ASC H COLPOSCOPY UNSATISFACTORY TZ not visible SATISFACTORY TZ fully visible Cytopathological Review Normal TZ Abnormal TZ Targeted Punch Biopsy AIS refer to management of cervical glandular abnormalities Cytopathological review and confirmed high grade cytology NEGATIVE / LSIL HSIL (CIN 2 / 3) Possible high grade Confirmed high grade cytology Repeat colpscopy and cytology within 6/12 Cytopathological review ABNORMAL NORMAL OPTIONS: Consider Cone Biospy Repeat Colposcopy and Cytology in 3/12 Consider second opinion Treatment Targeted Biopsy or Treatment Repeat Cytology 12/12 Definitive Treatment HPV TESTING (TEST OF CURE): An economic evaluation of HPV testing is being undertaken. This work will inform NCSP policy due for completion in mid 2007 REFERENCES: NHMRC (2005). Screening to Prevent Cervical Cancer: Guidelines for the Management of Asymptomatic Women with Screen Detected Abnormalities. NHMRC, Canberra. Histological confirmation of abnormality is recommended prior to treatment and is required before ablative therapy or hysterectomy is undertaken. There is no clearly superior method of fertility sparing treatment of CIN 2 and 3. 19

20 Table 3: Management of women with glandular abnormalities Women with cervical cytology report of Atypical glandular abnormalities Adenocarcinoma in situ (AIS) Adenocarcinoma COLPOSCOPY Normal TZ TZ Not Visible Assess TZ (for coexisting CIN) Cytopathologic Review Cytopathologic Review High Grade intraepithelial abnormality Overt Cancer CONE BIOPSY & D&C (except if pregnant)* OPTIONS: Observe Repeat cytology 3/12 & colposcopy Consider 2nd Opinion CONE BIOPSY & D&C (except if pregnant)* CONE BIOPSY & D&C (except if pregnant)* *See women in special circumstances (pregnancy). TARGET BIOPSY Adenocarcinoma CONSIDERATIONS: Type of excision Extent of excision Aim for assessable and negative margins Refer to gynaecological oncologist or gynaecological oncology unit for subsequent management 20

21 Appendix A: Guideline Development Team Mr Gary Fentiman (Chairman) Barbara Beckford Naomi Brewer Dr Alison Denyer Dr Peter Fitzgerald Dr Donna Hardie Mr Torben Iversen Dr Mona Jeffreys Obstetrician & Gynaecologist RANZCOG Consumer Representative Epidemiologist General Practitioner RNZCGP Cytopathologist RCPA (NZ) Obstetrician & Gynaecologist RANZCOG Obstetrician & Gynaecologist RANZCOG Epidemiologist Mr Peter Sykes Dr Ailing Tan Dr Mee-ling Yeong Gynaecological Oncologist RANZCOG Gynaecological Oncologist RANZCOG Cytopathologist RCPA (NZ) NSU Representatives Dr Hazel Lewis Jane McEntee Clinical leader, NCSP Manager, NCSP Dr Debbie Holdsworth Project Manager (until end December 2005) Diane Casey Senior Analyst (from November 2005) Project Manager (from January 2006) New Zealand Guidelines Group (NZGG) Anne Lethaby Jane Marjoribanks Project Administration Michelle Sampson Celina Prokopetz 21

22 Appendix B: Guideline Development Process In February 2005, the National Cervical Screening Programme (NCSP) of the Ministry of Health invited the New Zealand Guidelines Group (NZGG) to assist with the update of the Guidelines for the management of women with abnormal smears, published in The NZGG recommended a specific evidence-based methodology for the development of updated Guidelines. ( Guideline Development Team A multidisciplinary guidelines development group was established by the National Screening Unit (NSU) to update the current guideline. The group consisted of NSU representatives, one general practitioner, two epidemiologists, one consumer, two gynaecological oncologists, two pathologists and three experienced colposcopists, one of whom represented the rural sector. Mr Gary Fentiman chaired the group. Process The first meeting of the guideline development team (GDT) was held on 26 April The purpose of the meeting was to provide training on guideline development processes for members of the GDT and agree on the scope of the guideline. The group members made decisions on inclusion and exclusion of relevant topics to be covered by the guideline. Potential clinical questions were sent out to GDT members prior to the meeting and these were discussed and added to. These preliminary questions were posted on a secure NSU website for further discussion over the following two weeks before being finalised. The GDT decided to use the 1999 New Zealand guideline document as a basis for looking at new evidence that had become available since its publication. The recently published Australian guideline, Guidelines for the management of asymptomatic women with screendetected abnormalities (June 2005), was used as a major resource and its recommendations considered in the New Zealand context. During this scoping phase, a comprehensive search was made for all guidelines addressing the management of abnormal smears. The guidelines were critically appraised using the AGREE tool (Appendix C) and documents were prepared comparing their recommendations with the recommendations from the 1999 NZ guideline. Research In order to identify studies relevant to the questions of interest the NZGG comprehensively searched the following electronic databases: MEDLINE, MEDLINE-in process, EMBASE, the specialised trials register maintained by the Cochrane Gynaecological Cancer Group, the Cochrane Central Register of Controlled trials (CENTRAL), the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effectiveness (DARE), Cancerlit, HealthSTAR, CINAHL and the Health Technology Assessment (HTA) database. The databases were searched up to August 2005 for studies published in the English language. No unpublished literature was considered relevant because of concerns about quality. NZGG used the following medical subject headings (MESH) in Ovid databases: Vaginal smears, Cervix neoplasms, Cervical intraepithelial neoplasia, Papillomavirus, human Cervix dysplasia 22

23 The above MESH terms were combined with the following text words: Pap, smear, cervical, cytology, atypia, atypical, abnormality, dyskaryosis, dyskaryotic, dysplasia, dysplastic, ASCUS, AGUS, AGC, ASC-H, borderline, squamous, LBC, CIN, HSIL, HGSIL, LGSIL, LSIL, low-grade, high-grade, HGSIL, HSIL, epithelial, HPV, papilloma virus, HC2, Hybrid Capture, pregnant, pregnancy, immunosuppressed, immunosuppression, immunocompromised, immunodeficient, HIV, hysterectomy, hysterectomized Additionally, potential relevant studies were identified from the references of studies identified by the search, the references of review articles and the references of guidelines for the management of abnormal cervical smears produced in Australia, the United States of America, the United Kingdom and Canada. In-press publications were sought by personal contact with the authors. The identified studies were checked against the clinical questions, and studies that answered the specific questions were considered eligible for retrieval and included in the development of the evidence tables. In general studies published before 1998 were excluded as previous evidence is incorporated in the 1999 guidelines. However studies published before 1998 were considered where more recent evidence was unavailable. Critical appraisal The abstracts of potentially relevant studies were reviewed by NZGG staff for relevance to the questions and quality criteria. Full copies of the papers were retrieved where the inclusion criteria were met. Articles that did not address the questions were excluded from the review process and a list was made of these studies and the reasons for their exclusion. All included studies, except for case series, were appraised for quality using relevant checklists developed by the Scottish Intercollegiate Guidelines Network (SIGN) ( These were modified to incorporate summary levels of evidence for validity, precision and applicability. In addition, an overall summary level of evidence was assigned to each study. Evidence tables were then prepared for each of the clinical questions. The standard format for these tables includes columns covering the following descriptive data in addition to identification of the study, its type, and its methodological quality: Number of patients included in the study Characteristics of the patient population Intervention, risk factor, etc. being investigated in the study Comparisons made in the study Length of follow-up Outcome measures used Effect size, including statistical measures such as p values or confidence intervals Specific issues raised by the study that are relevant to the question being addressed. Summaries and considered judgement forms were prepared from the evidence tables to provide a basis for the development of recommendations. The considered Judgment form process has been developed by SIGN and has been modified by NZGG for New Zealand use ( These forms provide a format for considering the totality of evidence that has been identified to answer the questions. Issues such as quantity and consistency of the evidence, applicability and clinical impact are considered as a basis for the development of 23

24 recommendations. The evidence tables, considered judgment forms and summaries were sent out to GDT members prior to the 2 nd, 3 rd and 4th meetings. Development of Recommendations Three meetings were held for the development of recommendations based on the evidence tables, summaries and considered judgment forms. These took place on 21 September, 11 October and 29 November The GDT members considered the summary of evidence statements for each question and developed recommendations based on these summaries. For many questions, there was insufficient or inconsistent external evidence to provide direct answers. Some questions required extrapolation as there was no clear guidance from the evidence. In such situations, recommendations were developed by discussion, considered judgment and consensus. Subjective judgments were made but the likelihood of bias was minimised by requiring the consensus of the entire multidisciplinary group. Grading of the recommendations was based on the strength of the evidence ( entid=24&articleid=69), which should not be confused with importance. When there was no evidence to answer a specific question and recommendations were based on the consensus of the GDT, these recommendations were classified as Good Practice Points. The NZGG Grading system is found in Appendix E. The NSU undertook an analysis of data from the National Cervical Screening Programme Register. These analyses were to ensure that the updated guideline recommendations are relevant to the New Zealand situation see Appendix F. 24

25 Appendix C: AGREE Tool This tool was used for the appraisal of 5 evidence-based guidelines on the management of cervical abnormalities. UK ICSI Aus ASCCP Ontario 1. The overall objectives of the guideline are specifically **** ** **** **** ** described 2. The clinical questions covered by the guideline are *** *** **** ** **** specifically described 3. The patients to whom the guideline is meant to apply *** **** **** **** **** are specifically described 4. The guideline development group includes individuals ** **** **** **** *** from all the relevant professional groups 5. The patients' views and preferences have been sought * * *** * * 6. The target users of the guideline are clearly defined *** *** *** *** *** 7. The guideline has been piloted among target users * * **** ** * 8. Systematic methods were used to search for evidence * * **** *** **** 9. The criteria for selecting the evidence are clearly * * **** **** **** described 10. The methods used for formulating the * * ** **** ** recommendations are clearly described 11. The health benefits, side effects and risks have been *** *** *** *** *** considered in formulating the recommendations 12. There is an explicit link between the recommendations **** *** *** *** *** and the supporting evidence 13. The guidelines has been externally reviewed by * * **** **** **** experts prior to its publication 14. A procedure for updating the guideline is provided NR **** **** NR NR 15. The recommendations are specific and unambiguous **** *** **** *** **** 16. The different options for management of the condition **** *** **** **** ** are clearly presented 17. Key recommendations are easily identifiable **** *** **** **** **** 18. The guideline is supported with tools for application * * ** * * 19. The potential organisational barriers in applying the recommendations have been discussed 20. The potential cost implications of applying the recommendations have been considered 21. The guideline presents key review criteria for monitoring and/or audit purposes 22. The guideline is editorially independent from the funding body 23. Conflicts of interest of guideline development members have been recorded * *** *** * * * * *** * * **** **** **** * * NR NR NR NR NR * **** * **** **** The scoring system ranges from 1 to 4, with 1 being strongly disagree and 4 being strongly agree. The document uses stars that correspond to the numbers. AGREE questions 8-14 represent the Rigour of Development domain and the percentage scores for each guideline have been graphed for Appendix D: Rigor Score. 25

26 Appendix D: Rigor Score The Rigor Score below shows a graphed summary of questions 8 to 14 from the AGREE Tool. Note that the Australian Guideline scored highest. Rigour Score - Cervical Cancer Screening Guidelines Percentage UK ICSI AUS ASCCP Ontario Evidence based guidelines 26

27 Appendix E: New Zealand Grading System Grade A B C I Details The recommendation is supported by GOOD evidence (there are a number of studies that are valid, consistent, applicable and clinically relevant) The recommendation is supported by FAIR evidence (based on studies that are valid, but there are some concerns about the volume, consistency, applicability and/or clinical relevance of the evidence that may cause some uncertainty, but are not likely to be overturned by other evidence) The recommendation is supported by EXPERT OPINION only (from external opinion, published or unpublished, e.g. consensus guidelines) No recommendation can be made The evidence is lacking, of poor quality or conflicting and the balance of benefits and harms cannot be determined. Good practice point Where no external evidence is available, best practice recommendations are made by consensus, based on the experience of the Guideline Development Team, or feedback from consultation within New Zealand 27

28 Appendix F: NCSP Register Data Analysis Analysis of NCSP-R data relating to the Management of Women with Abnormal Smears National Cervical Screening Programme 28 November 2005 Contents 1. Background 2. Risk of HSIL in the 24 months following a first LSIL smear in Risk of HSIL in the 24 months following a first ASCUS smear in Estimated number of additional cancers per year resulting from change in recall interval from 6 to 12 months 5. Conclusion 28

29 1. Background This analysis was undertaken at the request of the NCSP Guideline Development Team and is intended to contribute to the development of the guideline for the management of women with abnormal smears. It addresses the issue of the optimal timing of recall in relation to a first abnormal smear. That is, it asks the question: can the NCSP safely extend the recommended time interval (currently 6 months) for recalling women following a first low grade smear (LSIL or ASCUS)? The analysis is based on the data held in the NCSP-R (extracted by Rosalyn Braganza). The analysis was carried out by Mona Jeffreys (Centre for Population Health Research, Massey University) except for the calculation of incremental cancers expected from a change in average recall interval, which was done by Martin Tobias (Public Health Intelligence). The data extraction and analysis were independently peer reviewed by Craig Wright (Public Health Intelligence). The final report was collated by Hazel Lewis (NSU). 2. Risk of HSIL in the 24 months following a first ASCUS smear in 2001 Key Points From analysis of women with a normal smear history and a first ASCUS in 2001, the following results were found: The two year risk of HSIL or worse histology was 16.4%. The longer the period between the ASCUS smear and the histology being taken, the higher the risk of HSIL. If colposcopy is delayed, the relative effect will be the same in young and older women, but the absolute risk of HSIL or worse will be greater in younger women, due to the higher underlying risk in this age group. Methods All women who had a previous normal smear history followed by an ASCUS smear in 2001 were identified through the NSCP-Register. The colposcopy outcomes for these women over the following 24 months were then examined. Outcome was classified as HSIL or worse or other. Results In 2001, 2,930 women who had an ASCUS smear following a previous normal smear history were identified. Of these, the time to next contact (smear or colposcopy) is shown in Table 1. Younger women (<30 years) were less likely to be followed up within nine months than older women (>=30 years), 25% vs. 14%, P<0.001, see Table 2. Table 1: Time to next contact following an ASCUS smear n Percent 0 to 8 months 2, to 15 months to 23 months or more months Total 2,

30 Table 2: Time to next contact following an ASCUS smear by age group <30 years >=30 years 0 to 8 months 913 (74.6%) 1,459 (85.5%) 9 to 15 months 221 (18.1%) 193 (11.3%) 16 to 23 months 65 (5.3%) 34 (2.0%) 24 or more months 25 (2.0%) 20 (1.2%) Risk of HSIL histology or worse Of the 2,930 women, 647 (22%) who did not have colposcopy within the subsequent 24 months were excluded from subsequent analysis. Of the remaining 2,283 women, the risk of having an HSIL or worse outcome on histology in a 24 month period was 16.4%. Younger women (age < 30) were much more likely to develop a HSIL or worse abnormality in the two year follow up than older women (24.1% vs. 11.0%, p<0.001). The longer the period between the ASCUS smear and the histology being taken, the higher the risk of HSIL (Table 3). Every extra month that the histology was delayed over the two year period was associated with a 9% higher risk of having a HSIL or worse outcome (odds ratio 1.09, 95% confidence interval 1.06 to 1.12, p<0.001). The same pattern of higher risk with delayed colposcopy was evident in younger and older women, although the numbers were small. Although the relative risk of HSIL or worse outcome for women who waited 16 to 23 months compared with those who waited under 9 months were similar in younger and older women, the absolute numbers of HSIL or worse will be greater in younger women, due to the higher underlying risk in this group. Table 3: Risk of developing HSIL or worse histology in the two years following an ASCUS smear by time delay between smear and colposcopy All women Age < 30 Age 30+ n Risk n Risk n Risk 0 to 8 months % % % 9 to 15 months % % % 16 to 23 months % % % Total % % % 3. Risk of HSIL in the 24 months following a first LSIL smear in 2001 Key Points From analysis of women with a normal smear history and a first LSIL in 2001, the following results were found: The two year risk of HSIL or worse histology was 22.7%. The longer the period between the LSIL smear and the histology being taken, the higher the risk of HSIL. If colposcopy is delayed, the relative effect will be the same in young and older women, but the absolute risk of HSIL or worse will be greater in younger women, due to the higher underlying risk in this group. 30