13. Screening after total hysterectomy

Total hysterectomy involves the removal of the cervix and the uterus and closure of the top of the vaginal canal, creating a vaginal vault. Removal of the cervix eliminates the risk of developing a cervical cancer and the need for cervical cytology. However, cytology of the vaginal vault can enable screening for pre-invasive disease of the vagina such as vaginal intraepithelial neoplasia (VAIN) or recurrence of previously treated cervical or vaginal cancer.

High-grade cervical intraepithelial neoplasia (CIN), prior to or at the time of total hysterectomy, is a known risk factor for the development of secondary VAIN, with reported recurrence rates of 0.9–7.4%.[1] However, VAIN is far less common than CIN and the incidence of vaginal cancer is less than a third of the incidence of cervical cancer, accounting for less than 0.5% of all cancers in Australian women.[2]

Based on an analysis of data from long-term follow-up studies conducted in women treated for high-grade CIN, Soutter et al found that, in the context of cytology follow-up after hysterectomy, the rate of invasive disease remained elevated in comparison with the rate in the general population, until at least 20 years after treatment.[3] Long-term vaginal cytology follow-up of hysterectomised women with a history of high-grade CIN has been recommended, but it should be noted that this recommendation was prior to the introduction of HPV testing.[3] Pre-renewal National Cervical Screening Program (NCSP) guidelines[4] recommended that women undergoing hysterectomy for high-grade CIN should be advised to continue annual cytologic surveillance, and noted the need for further investigation of the role of human papillomavirus (HPV) testing for this group.

Since 2006 under the pre-renewal NCSP, co-testing with HPV testing and cervical cytology has been used in Australia in the follow-up of women treated for high-grade CIN by ablation or excision of the transformation zone (TZ). A negative co-test is defined as a test occasion at which oncogenic HPV is not detected and the cytology report is negative. Women with two consecutive negative co-testing results during annual co-testing were returned to routine 2- yearly screening. This ‘Test of Cure’ approach, is based on the high negative predictive value of co-testing in identifying women at risk of recurrence. Comparison of screening outcomes for this strategy with those under pre-2006 guidelines, has shown this strategy to be safe.[5]

At this time it is uncertain whether a shorter period of surveillance could be recommended in the future. The safety of discharging women back to routine screening after only one occasion on which oncogenic HPV is not detected, or only one negative co-test, has not yet been conclusively established in Australia.

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Structured literature searches were conducted to ascertain the effectiveness of further screening with vaginal vault cytology or HPV tests in hysterectomised women in each of the following groups:

1. women who have never had abnormal cytology or a positive oncogenic HPV test result
2. women with a history of a positive oncogenic HPV test result and cytological prediction of a high-grade lesion (squamous or glandular), or women who have recently completed treatment for a high-grade lesion who are under surveillance or have returned to routine screening after treatment, with no evidence of abnormality on the hysterectomy specimen
3. women who have had a high-grade abnormality treated by total hysterectomy, with complete excision of the lesion in the hysterectomy specimen
4. women who had completed Test of Cure after treatment for CIN2+ before hysterectomy, with no abnormality in the hysterectomy specimen.

Three relevant recent articles were identified that reported data from women who had undergone total hysterectomies for benign conditions. In a prospective study, 4% of women (4 cases out of 102) who had undergone hysterectomy for uterine fibromatosis developed VAIN after a mean latency period of 10 years. All cases tested HPV16 positive at the time of VAIN diagnosis and had a positive cytology test. Two years after treatment for VAIN, two women previously diagnosed with VAIN 3 recurred and tested HPV16 positive at the time of relapse.[6] The presence or absence of any abnormal cytology or HPV history could not be ascertained from the articles.[7][8] Based on aggregated data from studies identified by a systematic review of the literature, Stokes-Lampard et al reported that 1.8% of women who had had a hysterectomy for a benign indication had an abnormal smear and no cancers were detected.[7]

No relevant recent articles were identified that reported outcomes for women with a history of high-grade abnormalities who:

• had been treated and were undergoing surveillance
• had completed a Test of Cure and had returned to routine screening prior to having a total hysterectomy with no evidence of any abnormality in the hysterectomy specimen.

A small number of retrospective studies in women with abnormal vaginal cytology after hysterectomy were identified. Although based on small samples (15–125 women), the results of these studies suggested that women who have had a total hysterectomy for CIN should continue post-treatment surveillance.[9][1][10]

One small prospective study which aimed to identify prognostic factors for the development of VAIN found that oncogenic HPV DNA was identified in seven out of eight women who developed VAIN post-hysterectomy.[11]

Soutter et al [3] performed a meta-analysis of 26 cohorts who had received treatment for CIN, including four cohorts who received hysterectomy treatment. They found that there was no significant difference in the incidence of invasive recurrence between those series in which women were treated with a total hysterectomy and those in which one of the conservative methods of treatment (ablation or excision) was used. The authors concluded that follow-up for women after hysterectomy for CIN should be the same as for women treated conservatively.[3]

Taken together, these findings provide evidence to support ongoing surveillance for hysterectomised women with a history of high grade CIN, but apply to screening and surveillance using cervical cytology alone. These findings are less relevant to the renewed NCSP, which is based on primary HPV testing, and within which post-treatment surveillance is based on co-testing (HPV and LBC).

Women who have had a total hysterectomy do not need further surveillance if both the following conditions apply:

• The woman has been treated for histologically confirmed HSIL and has completed Test of Cure according to pre-renewal NCSP guidelines[4] implemented since 2006.
• No evidence of cervical pathology was detected on the hysterectomy specimen.

Women who have had a total hysterectomy should be advised to complete Test of Cure if they have been treated for histologically confirmed HSIL, but have not completed Test of Cure.

Women who have had a total hysterectomy (for any of the reasons listed in Flowchart 13.1) and who have completed Test of Cure do not need any further surveillance or testing.

Women who have had subtotal hysterectomy (cervix remains in situ) should be screened every 5 years with a HPV test. Any abnormalities should be managed according to the relevant recommendations in these guidelines.

Flowchart 13.1. Vaginal screening after total hysterectomy

Table 13.1. Total hysterectomy

Note: If invasive cervical cancer reported in cervical pathology, patient to be referred to gynaecological oncologist for further management.

Total hysterectomy

Subtotal hysterectomy

For women who have had a total hysterectomy, who have a prior history of histologically confirmed HSIL, there is evidence to support continued surveillance for a limited period of time. For women who have had a hysterectomy with a prior history of AIS there is currently no evidence to inform the decision to discontinue surveillance. The potential harms of surveillance are minimal, especially in relation to the enhanced safety conferred by continuing surveillance.

See Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed NCSP.

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Clinical practice

These recommendations are generally consistent with current clinical practice, apart from the addition of HPV testing, to enhance recommended surveillance.

Resourcing

No material changes to the costs are anticipated.

Barriers to implementation

Women may not understand the importance of follow-up after total hysterectomy, believing that they are now ‘cured’. The treating gynaecologist should be encouraged to provide appropriate information regarding the risk of recurrent disease in the vagina, the need for surveillance and should provide the general practitioner with a management plan outlining the recommended surveillance.

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Unresolved issues

In the future, it is possible that women who have had a total hysterectomy may be discharged after test of cure following only one negative co-test, or a single HPV-only test, but sufficient data to support such management will need to be accrued via the safety monitoring process for the NCSP.

Future research priorities

Currently there is insufficient evidence to determine the most appropriate follow-up for patients who have had AIS and had a total hysterectomy. Research to inform the method and duration of follow up of these women should be given priority.

A prospective audit of a large cohort of women undergoing hysterectomy for benign reasons with a history of high grade CIN (potentially via the safety monitoring of the NCSP) is needed to provide the evidence required to ascertain the appropriate frequency, duration and test modality for follow-up testing from the vaginal vault.

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