Q&a attempts to provide balanced answers to those curly-yet-common questions in obstetrics and gynaecology for the broader O&G Magazine readership, including Diplomates, Trainees, medical students and other health professionals.
‘What is the role of vaginal cytology after hysterectomy?’
Pap smears of the vaginal vault aim to detect invasive or pre-invasive disease of the vagina in women who no longer have a cervix. Vaginal intraepithelial neoplasia (VAIN) is much less common than cervical intraepithelial neoplasia (CIN), with an incidence of 0.2 to 0.3 per 100 000 women.1 Vaginal cancer has an incidence of 0.7 per 100 000 women2, making it a rare gynaecological malignancy.
A recent study on vaginal cytology in women who underwent a hysterectomy owing to gynecological malignancy, CIN 3 or benign gynecological diseases, indicated that VAIN lesions occurred in these groups at a rate of 7.1 per cent, 3.0 per cent, and 0.5 per cent, respectively.3 Given the low prevalence of VAIN and vaginal cancer, available evidence indicates a low positive predictive value for vaginal cytology when used as a screening tool in the absence of symptoms or clinical signs.3,4
Hysterectomy for benign disease
Abnormal cytology is found in less than two per cent of vaginal cuff smears after hysterectomy for benign disease.1,2,3 Collating data from more than 6000 women, Stokes-Lampard et al reported that subsequent to hysterectomy for benign indications, 1.8 per cent of women had an abnormal vaginal vault smear, 0.12 per cent had an abnormal biopsy and no cancers were identified.2
Current recommendations are that women who have undergone hysterectomy for benign conditions at any age, who have a history of normal Pap smears and whose cervical histology shows no dysplasia or malignant change, should not be screened for VAIN or vaginal cancer using any modality as they are at minimal risk. In women where a normal Pap smear history is not available or where histology of the hysterectomy specimen is not available, a baseline Pap smear of the vaginal vault can be performed. If this is negative, further smears are only required as indicated by symptoms.5
Women who have had a subtotal hysterectomy where the cervix remains in situ require ongoing cervical cytology as per national screening guidelines for the prevention of cervical cancer.5
Hysterectomy for cervical dysplasia
Hysterectomy for CIN is a known risk factor for the subsequent development of VAIN, with reported rates ranging from 0.9 to 6.8 per cent.6 In a systematic review, women who underwent hysterectomy for CIN 3 had an incidence of abnormal vault smears of 14 per cent. However, less than two per cent of patients had an abnormal biopsy and only a single case of vaginal cancer was detected (0.03 per cent). 86 per cent of abnormal smears occurred within two years of hysterectomy.2 Shockaert et al detected VAIN 2+ in 7.4 per cent of women who had Pap smears after hysterectomy for CIN 2/3 or Stage 1A 1 cervical carcinoma.6 Women who developed VAIN 2+ after hysterectomy were significantly older than women that did not. The median interval between hysterectomy and biopsy proven VAIN 2+ was 35 months.6 These data would indicate that these women remain at risk of VAIN following hysterectomy for high-grade cervical dysplasia, particularly in the first two years.
This risk of developing subsequent VAIN is largely determined by the adequacy of excision of the CIN or ACIS at the time of hysterectomy. If excision margins are involved with high-grade dysplasia or not adequately assessed by histology of the hysterectomy specimen, there is an increased risk of VAIN or invasive cancer in the region of the vault. Vaginal vault smears and vaginal colposcopy should continue to be performed annually, with directed biopsies if required.5 When a high-grade lesion (CIN 2/3 or adenocarcinoma in situ) has been completely excised at hysterectomy it is reasonable for women to undergo annual vault cytology for five years and if results are normal, thereafter revert to the recommended screening interval.5
Women with previously treated CIN 2/3 who have subsequent normal Pap smears, negative high-risk human papillomavirus (HPV) DNA testing and have no residual disease on histology of the cervix, should continue to have vaginal cytology at the recommended screening interval until such evidence is available to indicate that clearing the HPV virus from the cervix also indicates its clearance from the vagina.5
Women with a history of low-grade CIN who have reverted to normal cervical cytology prior to hysterectomy do not need vaginal vault smears, unless symptomatic.
Hysterectomy for invasive cervical cancer
The vagina is a common site for recurrent cervical and the early detection of these recurrences is aimed at treating patients with potentially curative salvage therapy.
Although most guidelines suggest vaginal cytology after hysterectomy for cervical carcinoma at each follow-up visit7,8, the effectiveness of Pap smears in this context is not well studied. Clinical symptoms and physical examination will detect the majority of recurrences with few cervical cancer recurrences being detected by vaginal cytology alone.9,10,11 Furthermore, the interpretation of cytology can be problematic in those patients who have been treated with adjuvant radiotherapy.
In a review of 13 trials on follow up of cervical cancer, asymptomatic recurrent disease was detected using vaginal vault cytology in 0–17 per cent of cases.12 Injumpa et al showed that the detection rate of vaginal recurrences by vaginal cytology was only 2.4 per cent, with the test having poor sensitivity.13
The majority of cervical cancer recurrences occur in the first two-to-three years after treatment3 and >90 per cent have occurred by five years.12 Li et al in their cohort of women with cervical squamous cell carcinoma, treated with hysterectomy, found that all vaginal high-grade dysplasia and recurrent squamous cell cancers were detected in the first two years of follow up.1
Current surveillance recommendations for women following treatment for cervical cancer include annual vaginal cytology and thorough examination of the vaginal vault to detect local recurrence and pre-invasive disease in the vagina.
The role of high-risk HPV DNA testing in women treated for invasive cervical cancer or high-grade cervical dysplasia after hysterectomy is not clear and requires further investigation.5 With the introduction of new cervical cancer screening guidelines, based on primary HPV testing, due to take place in Australia and New Zealand, we await further monitoring data to advise on the utility of HPV-based testing in the post-hysterectomy population.
Hysterectomy for endometrial cancer
Following treatment of endometrial cancer, approximately three-to-five per cent of patients will experience a local recurrence of disease confined to the vagina and central pelvis11,14 that may be salvaged with curative therapy. More than 80 per cent of these women will present with vaginal bleeding or have a clinically apparent lesion in the vagina.14 Hence, a history of vaginal bleeding and careful visual examination and palpation of the vaginal vault will identify the vast majority of patients that need further evaluation for recurrent disease.
Vaginal cytology alone is ineffective at identifying vaginal recurrences in asymptomatic patients, with less than one per cent of asymptomatic vaginal recurrences are detected by routine vaginal cytology.14,15 Finally, a significant survival advantage has not been demonstrated for patients whose recurrences are detected during routine follow-up visits compared with patients who present for internal examinations owing to the onset of symptoms.14,15
Hence, routine vaginal cytology in asymptomatic women under surveillance after hysterectomy for endometrial adenocarcinoma is no longer recommended.
Other high-risk populations
Women previously treated for VAIN remain at risk and should continue to have vaginal cytology post hysterectomy, every one-to-two years, dependent on patient risk factors, extent of VAIN and completeness of excision. Women with a past history of HPV-related vulval or anal dysplasia or malignancy should also continue to have vaginal cytology at one-to-two yearly intervals.
Similarly, immunocompromised women are predisposed to squamous cell malignancy of the lower genital tract and should be followed up with vaginal cytology every two years and annually if they have a past history of lower genital tract dysplasia.
Women who were exposed to diethylstilboestrol (DES) in utero are at increased risk for clear cell cancer of the vagina and cervix and should continue to have vaginal Pap smears and careful palpation of the vaginal walls at one-to-two yearly intervals after hysterectomy.
In conclusion, vaginal cytology for vaginal cancer screening is advisable for women who have undergone total hysterectomy if they have the following characteristics:
- prior vaginal high-grade dysplasia or cancer;
- prior cervical, vulval and anal dysplasia or cancer;
- CIN 2/3 or cervical adenocarcinoma in situ diagnosed at hysterectomy;
- in utero exposure to DES; or
- immunosuppression (for example, HIV, history of solid organ orhaematopoietic cell transplant).
Routine vaginal cytology is no longer recommended in asymptomatic women after hysterectomy for benign conditions or treatment of endometrial adenocarcinoma.