The Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Cytological follow-up after hysterectomy

Objectives: To provide advice on the cytological follow up after hysterectomy. This statement has been developed and reviewed by

the Women’s Health Committee and approved by the RANZCOG Board and Council. Target audience: Health professionals providing gynaecological care, and patients. A list of Women’s Health Committee Members can be found in Appendix A. Values: The evidence was reviewed by the Women’s Health Committee (RANZCOG), and Disclosure statements have been received from all applied to local factors relating to Australia and members of this committee. New Zealand.

Background: This statement was first developed by Disclaimer This information is intended to provide Women’s Health Committee in November 2010 general advice to practitioners. This information and reviewed in November 2015. should not be relied on as a substitute for proper assessment with respect to the particular Funding: The development and review of this circumstances of each case and the needs of any statement was funded by RANZCOG. patient. This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The document has been prepared having regard to general circumstances.

First endorsed by RANZCOG: November 2010 Current: November 2015 Review due: November 2018

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Table of contents

1. Summary of recommendations ...... 3 2. Introduction ...... 4 3. Discussion and recommendations...... 4 3.1 Hysterectomy for benign reason ...... 4 3.2 Indications for continued evaluation...... 4 3.2.1 Sub-total hysterectomy ...... 4 3.2.2 Women for whom the Papanicolaou smear history and/or the histology from the hysterectomy is not known ...... 4 3.2.3 Women with a past history of pre-invasive disease of the cervix………………………………...4 3.2.4 Women previously treated for invasive gynaecological malignancy ...... 5 3.2.5 Women previously treated for vaginal intraepithelial neoplasia (VAIN) ...... 5 3.2.6Women who are severely immunosuppressed as the result of disease or therapy ...... 5 3.2.7 Women who were exposed to DES (diethylstilboestrol) in utero ...... 5 4. References ...... 6 5. Other suggested reading ...... 6 6. Links to other College statements ...... 6 7. Patient information ...... 6 Appendices ...... 7 Appendix A Women’s Health Committee Membership ...... 7 Appendix B Overview of the development and review process for this statement ...... 7 Appendix C Full Disclaimer ...... 9

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1. Summary of recommendations

Recommendation 1 Grade Women who have undergone hysterectomy for benign disease (such as menstrual Reference 1 problems or prolapse), have a history of normal Pap smears, and whose histopathology of the cervix shows no neoplastic or premalignant change are at minimal risk for the development of vaginal cancer. It is therefore recommended that these women need not, have any further screening Pap smears.1

Recommendation 2 Grade Women who have undergone sub-total hysterectomy in the past, that is the cervix has not Consensus-based been removed, should continue to have smears at the recommended interval as a recommendation screening for the prevention of cervical cancer.

Good Practice Point Grade If the woman’s Papanicolaou smear history and/or the histology from the hysterectomy is Consensus-based not available it would be prudent to obtain a base-line Pap smear from the vaginal vault at recommendation the time of consultation. If this is normal then the woman is probably at a very small risk for the development of vaginal cancer and further smears are only required as clinically indicated.

Recommendation 3 Grade When a high grade lesion (CIN2-3/ACIS) has been completely excised at hysterectomy, Consensus-based there may also be an increased risk of VAIN, recurrent VAIN or invasive cancer because of recommendation field change of the lower genital tract. The exact risk of this is difficult to quantify but it seems reasonable that these women should continue to have Pap smears taken from the vaginal vault annually for five years and thereafter revert to the recommended screening interval, as for those with a residual cervix.

Recommendation 4 Grade Women who have previously had a Pap smear or cervical biopsy with LSIL, (Low grade Consensus-based squamous intraepithelial lesion) and who had reverted to normal cervical cytology prior to recommendation hysterectomy do not need vaginal vault smears, unless they are symptomatic.

Recommendation 5 Grade Some women who have previously been treated for invasive gynaecological malignancy Consensus-based are at risk for recurrent disease in the region of the vaginal vault. Women treated for recommendation carcinoma of the cervix and endometrium, have traditionally had vaginal vault smears as part of routine surveillance. Pap smears for these groups should be at the discretion of the treating gynaecological oncologist.

Recommendation 6 Grade Women previously treated for vaginal intraepithelial neoplasia (VAIN) are at risk for Consensus-based development of VAIN in other parts of the vagina as this disease may be multifocal. They recommendation should continue to have Pap smears or vaginal vault cytology every 1-2 years or at the discretion of their treating specialist.

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2. Introduction

Modern gynaecological practice is to perform a total hysterectomy with removal of the cervix whenever feasible. For women who have had a total hysterectomy, the aim of taking Papanicolaou (Pap) smears from the vaginal vault is screening for the prevention of vaginal cancer. In 2003, there were 67 cases of vaginal cancer diagnosed,2 compared with 725 new cases of invasive cervical cancer in Australia. A Guidelines Working Group under the auspices of the Cancer Council Australia and funded by the Commonwealth Department of Health, have begun work on the new Clinical Management Guidelines for the National Cervical Screening Program (NCSP) which is expected to commence in mid-2017.

3. Discussion and recommendations

3.1 Hysterectomy for benign reason Women who have undergone hysterectomy for benign disease (such as menstrual problems or prolapse), have a history of normal Pap smears, and whose histopathology of the cervix shows no neoplastic or premalignant change are at minimal risk for the development of vaginal cancer. It is therefore recommended that these women need not, in the absence of symptoms, have any further Pap smears.1

3.2 Indications for continued evaluation Despite the rarity of vaginal cancer, some women are at a higher risk for the development of vaginal cancer and should continue to have Pap smears taken from the vaginal vault after hysterectomy.

3.2.1 Sub-total hysterectomy Women who have undergone sub-total hysterectomy in the past, that is the cervix has not been removed, should continue to have smears at the recommended interval as a screening for the prevention of cervical cancer.

3.2.2 Women for whom the Papanicolaou smear history and/or the histology from the hysterectomy is not known A significant proportion of women are unaware of their Pap smear results prior to hysterectomy and/or the exact results of any pathology. For many this information has not been readily available, although the presence of state and territory based cervical cytology registries should assist in accessing this information. If the information is not available it would be prudent to obtain a base- line Pap smear from the vaginal vault at the time of consultation. If this is normal then the woman is probably at a very small risk for the development of vaginal cancer and further smears are only required as clinically indicated.

3.2.3 Women with a past history of pre-invasive disease of the cervix The majority of women diagnosed as having vaginal intraepithelial neoplasia (VAIN) or vaginal cancer have had previous abnormal smears or cervical intraepithelial neoplasia (CIN2-3) at hysterectomy. The risk of development of VAIN, adenocarcinoma in situ (AIS) or vaginal cancer is mainly determined by the adequacy of excision of the CIN or ACIS at the time of hysterectomy.

• If the excision margin was involved or not adequately assessed histologically, the woman may be at considerable risk for VAIN or invasive cancer in the region of the vault, which may take years to become manifest. Follow-up should be at the discretion of the gynaecologist. Vault smears should in general be taken annually. There is no evidence to support a change in this policy.

• When a high grade lesion (CIN2-3/ACIS) has been completely excised at hysterectomy, there may also be an increased risk of VAIN, recurrent VAIN or invasive cancer because of field change of the lower genital tract. The exact risk of this is difficult to quantify but it seems reasonable that these Cytological follow up after hysterectomy C-Gyn 8 4

women should continue to have Pap smears taken from the vaginal vault annually for five years and thereafter revert to the recommended screening interval, as for those with a residual cervix. The role of high risk HPV DNA testing in this situation is uncertain and requires further investigation.3

• Women who have previously had a Pap smear or cervical biopsy with LSIL, (Low grade squamous intraepithelial lesion) and who had reverted to normal cervical cytology prior to hysterectomy do not need vaginal vault smears, unless they are symptomatic. This is in accordance with management of women with LSIL as described in the NHMRC guidelines.1

• Women with a past history of high grade squamous intraepithelial lesions of the cervix (CIN2-3), who have been treated and have subsequent normal Pap smears and are negative for high risk HPV DNA (‘test of cure’). These women would have returned 2 yearly cervical screening or in New Zealand 3 yearly. These women may subsequently have a hysterectomy for other reasons with no evidence of residual disease in the histology of the cervix. It seems likely that these women are at no greater risk than women who have not had previous HSIL, and that no further smears are indicated. However, this presumes that women who have cleared HPV from the cervix will also have cleared it from the vagina. There is no evidence to support this presumption and therefore it would seem prudent that women continue to have vaginal vault smears every two years, until further evidence suggests a more conservative approach. This advice will be strengthened by the monitoring reports related to the new guidelines.4

3.2.4 Women previously treated for invasive gynaecological malignancy Some of these women are at risk for recurrent disease in the region of the vaginal vault. Women treated for carcinoma of the cervix and endometrium, have traditionally had vaginal vault smears as part of routine surveillance. Most authorities note limited value of Pap smears in this situation in asymptomatic women particularly in endometrial cancer patients. Most gynaecological treatment centres are not performing Pap smears or vaginal vault cytology for endometrial cancer surveillance, but many continue to do annual smears for cervix cancer patients. Pap smears for these groups should be at the discretion of the treating gynaecological oncologist. Once these patients are discharged from subspecialist care it would be usual to perform annual vault smears indefinitely.

3.2.5 Women previously treated for vaginal intraepithelial neoplasia (VAIN) These women are at risk for development of VAIN in other parts of the vagina as this disease may be multifocal. They should continue to have Pap smears or vaginal vault cytology every 1-2 years or at the discretion of their treating specialist.

3.2.6Women who are severely immunosuppressed as the result of disease or therapy Immune impairment is a predisposing factor for squamous cell malignancy of the lower genital tract. Data in this group of women who have had a hysterectomy for benign disease is limited. It would seem prudent that these women have vault smears every 2 years or in New Zealand 3 yearly.

3.2.7 Women who were exposed to DES (diethylstilboestrol) in utero These women are at increased risk for clear cell cancer of the vagina and cervix. The lifetime risk is very small (1:1000-10000) but in the absence of evidence to the contrary they should continue to have Pap smears from the vaginal vault and careful palpation of the vaginal walls at 1-2 yearly intervals after hysterectomy.

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4. References

1. NHMRC. Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen-detected abnormalities 2005. 2. Welfare AIoHa. Number of new cases and age standardised rates (Australia 2001 and World) for selected cancers by year of registration. 3. Solomon D BN, McNeel T. Cervical cancer screening rates in the United States and the potential impact of implementation of screening guidelines CA. , Cancer J Clin 2007;57:105-11. 4. Australian Institute of Health and Welfare (AIHW) CsiA-CsnCnCCA. Cervical screening in Australia 2011-2012, Cancer series no. 2014;82(no.CAN79).

5. Other suggested reading

Report on monitoring activities of the National Cervical Screening Program Safety Committee, Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129545152

Springer (2015) The Bethesda System for Reporting Cervical Cytology http://www.springer.com/us/book/9783319110738

6. Links to other College statements

Cervical Cancer Screening in Australia (C-Gyn 19) http://www.ranzcog.edu.au/component/docman/doc_download/2029-cervical-cancer-screening-in- australia-c-gyn-19.html?Itemid=946

Guidelines for referral of investigation of intermenstrual and postcoital bleeding (C-Gyn 06) http://www.ranzcog.edu.au/component/docman/doc_download/907-c-gyn-06-investigation-of- intermenstrual-and-postcoital-bleeding-.html

Evidence-based Medicine, Obstetrics and Gynaecology (C-Gen 15) http://www.ranzcog.edu.au/component/docman/doc_download/894-c-gen-15-evidence-based-medicine- obstetrics-and-gynaecology.html?Itemid=341

7. Patient information

A range of RANZCOG Patient Information Pamphlets can be ordered via:

http://www.ranzcog.edu.au/publication/womens-health-publications/patient-information pamphlets.html

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Appendices

Appendix A Women’s Health Committee Membership

Name Position on Committee Professor Stephen Robson Chair and Board Member Dr James Harvey Deputy Chair and Councillor Associate Professor Anusch Yazdani Member and Councillor Associate Professor Ian Pettigrew Member and Councillor Dr Ian Page Member and Councillor

Professor Yee Leung Member of EAC Committee Professor Sue Walker General Member Dr Lisa Hui General Member Dr Joseph Sgroi General Member Dr Marilyn Clarke General Member

Dr Donald Clark General Member Associate Professor Janet Vaughan General Member Dr Benjamin Bopp General Member Associate Professor Kirsten Black General Member Dr Jacqueline Boyle Chair of the ATSIWHC

Dr Martin Byrne GPOAC representative Ms Catherine Whitby Community representative Ms Sherryn Elworthy Midwifery representative Dr Nicola Quirk Trainee representative

Appendix B Overview of the development and review process for this statement i. Steps in developing and updating this statement

This statement was originally developed in November 2010 and was most recently reviewed in November 2015. The Women’s Health Committee carried out the following steps in reviewing this statement:

• Declarations of interest were sought from all members prior to reviewing this statement.

• Structured clinical questions were developed and agreed upon.

• An updated literature search to answer the clinical questions was undertaken.

• At the September 2015 teleconference, the existing consensus-based recommendations were reviewed and updated (where appropriate) based on the available body of evidence and clinical expertise. Recommendations were graded as set out below in Appendix B part iii)

ii. Declaration of interest process and management

Declaring interests is essential in order to prevent any potential conflict between the private interests of members, and their duties as part of the Women’s Health Committee.

A declaration of interest form specific to guidelines and statements was developed by RANZCOG and approved by the RANZCOG Board in September 2012. The Women’s Health Committee members

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were required to declare their relevant interests in writing on this form prior to participating in the review of this statement.

Members were required to update their information as soon as they become aware of any changes to their interests and there was also a standing agenda item at each meeting where declarations of interest were called for and recorded as part of the meeting minutes.

There were no significant real or perceived conflicts of interest that required management during the process of updating this statement. iii. Grading of recommendations

Each recommendation in this College statement is given an overall grade as per the table below, based on the National Health and Medical Research Council (NHMRC) Levels of Evidence and Grades of Recommendations for Developers of Guidelines. Where no robust evidence was available but there was sufficient consensus within the Women’s Health Committee, consensus-based recommendations were developed or existing ones updated and are identifiable as such. Consensus-based recommendations were agreed to by the entire committee. Good Practice Notes are highlighted throughout and provide practical guidance to facilitate implementation. These were also developed through consensus of the entire committee.

Recommendation category Description

Evidence-based A Body of evidence can be trusted to guide practice

B Body of evidence can be trusted to guide practice in most situations

C Body of evidence provides some support for recommendation(s) but care should be taken in its application

D The body of evidence is weak and the recommendation must be applied with caution

Consensus-based Recommendation based on clinical opinion and expertise as insufficient evidence available

Good Practice Note Practical advice and information based on clinical opinion and expertise

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Appendix C Full Disclaimer This information is intended to provide general advice to practitioners, and should not be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of any patient. This information has been prepared having regard to general circumstances. It is the responsibility of each practitioner to have regard to the particular circumstances of each case. Clinical management should be responsive to the needs of the individual patient and the particular circumstances of each case. This information has been prepared having regard to the information available at the time of its preparation, and each practitioner should have regard to relevant information, research or material which may have been published or become available subsequently. Whilst the College endeavours to ensure that information is accurate and current at the time of preparation, it takes no responsibility for matters arising from changed circumstances or information or material that may have become subsequently available.

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