13. Screening after total hysterectomy

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Background

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 (VAINVaginal intra-epithelial neoplasia) or recurrence of previously treated cervical or vaginal cancer.

High-grade cervical intraepithelial neoplasia (CINCervical Intraepithelial NeoplasiaRefers to abnormal changes in the cells on the surface of the cervix that are seen using a microscope (i.e. histologically-confirmed).CIN 1 – Mild dysplasiaCIN 2 – Moderate dysplasiaCIN 3 – Severe dysplasia to carcinoma in situ(The term CIN 2+ refers to CIN 2, 3, or invasive cervical cancer; CIN3+ refers to CIN 3 or invasive cervical cancer)CIN 2/3 refers to CIN 2 or CIN 3.), prior to or at the time of total hysterectomy, is a known risk factor for the development of secondary VAINVaginal intra-epithelial neoplasia, with reported recurrence rates of 0.9–7.4%.[1] However, VAINVaginal intra-epithelial neoplasia 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 CINCervical Intraepithelial NeoplasiaRefers to abnormal changes in the cells on the surface of the cervix that are seen using a microscope (i.e. histologically-confirmed).CIN 1 – Mild dysplasiaCIN 2 – Moderate dysplasiaCIN 3 – Severe dysplasia to carcinoma in situ(The term CIN 2+ refers to CIN 2, 3, or invasive cervical cancer; CIN3+ refers to CIN 3 or invasive cervical cancer)CIN 2/3 refers to CIN 2 or CIN 3., 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 (NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.) 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 (HPVHuman papillomavirus) testing for this group.

Since 2006 under the pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., co-testingHPV test and LBC both requested and performed on a cervical sample. 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 (TZTransformation zoneThis region of the cervix where the columnar epithelium has been replaced and/or is being replaced by the new metaplastic squamous epithelium is referred to as the transformation zone. It corresponds to the area of cervix bound by the original squamocolumnar junction at the distal end and proximally by the furthest extent that squamous metaplasia has occurred as defined by the new squamocolumnar junction. In premenopausal women, the transformation zone is fully located on the ectocervix. After menopause through old age, the cervix shrinks with the decreasing levels of estrogen. Consequently, the transformation zone may move partially, and later fully, into the cervical canal.The transformation zone may be described as normal when it is composed of immature and/or mature squamous metaplasia along with intervening areas or islands of columnar epithelium, with no signs of cervical carcinogenesis. It is termed an abnormal or atypical transformation zone (ATZ) when evidence of cervical carcinogenesis such as dysplastic change is observed in the transformation zone. Identifying the transformation zone is of great importance in colposcopy, as almost all manifestations of cervical carcinogenesis occur in this zone.). A negative co-testHPV test and LBC both requested and performed on a cervical sample. 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-testingHPV test and LBC both requested and performed on a cervical sample. results during annual co-testingHPV test and LBC both requested and performed on a cervical sample. were returned to routine 2-yearly screening. This ‘Test of Cure’ approach, is based on the high negative predictive value of co-testingHPV test and LBC both requested and performed on a cervical sample. 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-testHPV test and LBC both requested and performed on a cervical sample., has not yet been conclusively established in Australia.

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General literature review evidence

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 VAINVaginal intra-epithelial neoplasia after a mean latency period of 10 years. All cases tested HPV16 positive at the time of VAINVaginal intra-epithelial neoplasia diagnosis and had a positive cytology test. Two years after treatment for VAINVaginal intra-epithelial neoplasia, two women previously diagnosed with VAINVaginal intra-epithelial neoplasia 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 VAINVaginal intra-epithelial neoplasia found that oncogenic HPV DNA was identified in seven out of eight women who developed VAINVaginal intra-epithelial neoplasia post-hysterectomy.[11]

Soutter et al[3] performed a meta-analysis of 26 cohorts who had received treatment for CINCervical Intraepithelial NeoplasiaRefers to abnormal changes in the cells on the surface of the cervix that are seen using a microscope (i.e. histologically-confirmed).CIN 1 – Mild dysplasiaCIN 2 – Moderate dysplasiaCIN 3 – Severe dysplasia to carcinoma in situ(The term CIN 2+ refers to CIN 2, 3, or invasive cervical cancer; CIN3+ refers to CIN 3 or invasive cervical cancer)CIN 2/3 refers to CIN 2 or CIN 3., 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 CINCervical Intraepithelial NeoplasiaRefers to abnormal changes in the cells on the surface of the cervix that are seen using a microscope (i.e. histologically-confirmed).CIN 1 – Mild dysplasiaCIN 2 – Moderate dysplasiaCIN 3 – Severe dysplasia to carcinoma in situ(The term CIN 2+ refers to CIN 2, 3, or invasive cervical cancer; CIN3+ refers to CIN 3 or invasive cervical cancer)CIN 2/3 refers to CIN 2 or CIN 3., but apply to screening and surveillance using cervical cytology alone. These findings are less relevant to the renewed NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears., which is based on primary HPV testing, and within which post-treatment surveillance is based on co-testingHPV test and LBC both requested and performed on a cervical sample. (HPV and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.).


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Recommendations

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 HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). and has completed Test of Cure according to pre-renewal NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears. 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 HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., 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

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Table 13.1. Total hysterectomy

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


Total hysterectomy

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REC13.1: Total hysterectomy for benign disease
Women with a normal cervical screening history, who have undergone hysterectomy for benign disease (e.g. menorrhagia, uterine fibroids or utero-vaginal prolapse), and have no cervical pathology at the time of hysterectomy, do not require further screening or follow up.

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REC13.2: Total hysterectomy after completed Test of Cure
Women who have had a total hysterectomy with no evidence of cervical pathology, have previously been successfully treated for histologically confirmed HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). and have completed Test of Cure, do not require further follow-up. These women should be considered as having the same risk for vaginal neoplasia as the general population who have never had histologically confirmed HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). and have a total hysterectomy.

If unexpected LSILLow-grade squamous intraepithelial lesionThe low-grade squamous intraepithelial lesion (LSIL) category is the morphological correlate of productive viral infection. It is to be used when the scientist/pathologist observes changes that would have been described as ‘HPV effect’ or ‘CIN 1’ in the previous Australian terminology and represents part of the previous ‘low-grade squamous epithelial abnormality’ category. or HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). is identified in the cervix at the time of hysterectomy, then these women require follow-up with an annual co-testHPV test and LBC both requested and performed on a cervical sample. on a specimen from the vaginal vault until they have a negative co-testHPV test and LBC both requested and performed on a cervical sample. on two consecutive occasions.

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REC13.3: Total hysterectomy after adenocarcinoma in situ (AISAdenocarcinoma in situ)
Women who have had a total hysterectomy, have been treated for AISAdenocarcinoma in situ, and are under surveillance, should have a co-testHPV test and LBC both requested and performed on a cervical sample. on a specimen from the vaginal vault at 12 months and annually thereafter, indefinitely.

Women who have a total hysterectomy, as completion therapy or following incomplete excision of AISAdenocarcinoma in situ at cold-knife cone biopsy or diathermy excision, should have a co-testHPV test and LBC both requested and performed on a cervical sample. on a specimen from the vaginal vault at 12 months and annually thereafter, indefinitely.

Until sufficient data become available to support cessation of testing

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REC13.4: Total hysterectomy for treatment of high-grade CIN in the presence of benign gynaecological disease
Women who have had a total hysterectomy as definitive treatment for histologically confirmed HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). in the presence of benign gynaecological disease, irrespective of cervical margins, should have a co-testHPV test and LBC both requested and performed on a cervical sample. on a specimen from the vaginal vault at 12 months after treatment and annually thereafter until the woman has tested negative by both tests on two consecutive occasions.

After two annual consecutive negative co-tests, the woman can be advised that no further testing is required.

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REC13.5: Total hysterectomy after histologically confirmed HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology). without Test of Cure
Women who have been treated for histologically confirmed HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., are under surveillance or have returned to routine screening without Test of Cure, and have had a total hysterectomy with no evidence of cervical pathology, should have a co-testHPV test and LBC both requested and performed on a cervical sample. on a specimen from the vaginal vault at 12 months and annually until the woman has tested negative on two consecutive occasions.

After two annual consecutive negative co-tests, the woman can be advised that no further testing is required.

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REC13.6: Total hysterectomy and no screening history
Women who have had a total hysterectomy with no evidence of cervical pathology, and whose cervical screening history is not available, should have a HPV test on a specimen from the vaginal vault at 12 months and annually thereafter until they have a negative HPV test on two consecutive occasions.

After two annual consecutive negative HPV tests, women can be advised that no further testing is required.

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REC13.7: ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. referral for any positive co-testHPV test and LBC both requested and performed on a cervical sample. result following total hysterectomy
Women who have had a total hysterectomy and are under surveillance with co-testingHPV test and LBC both requested and performed on a cervical sample., and have a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result and/or any cytological abnormality, should be referred for colposcopic assessment.

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REC13.8: Vaginal bleeding following total hysterectomy
Women who have vaginal bleeding following total hysterectomy should be assessed by their GP or gynaecologist, regardless of the results of any surveillance tests.

Vaginal bleeding is quite common in the early weeks following hysterectomy and, where appropriate, should be investigated by the treating gynaecologist.

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REC13.9: Total hysterectomy after genital tract cancer
Women who have been treated for cervical or endometrial cancer are at risk of recurrent cancer in the vaginal vault. These women should be under ongoing surveillance from a gynaecological oncologist. Therefore, they will be guided by their specialist regarding appropriate surveillance and this is outside the scope of these guidelines.

Subtotal hysterectomy

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REC13.10: Subtotal hysterectomy
Women who have undergone subtotal hysterectomy (the cervix is not removed) should be invited to have 5-yearly HPV testing in accordance with the recommendation for the general population. Any detected abnormality should be managed according to these guidelines.

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Benefits and harms

For women who have had a total hysterectomy, who have a prior history of histologically confirmed HSILHigh-grade squamous intraepithelial lesionIn the Australian context, HSIL is used to refer to a cytology predictive of a high grade precancerous lesion (AMBS 2004), or histologically confirmed high grade precancerous lesion (HSIL-CIN2 or HSIL-CIN3 as per LAST terminology)., 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 AISAdenocarcinoma in situ 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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Health system implications of these recommendations

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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Discussion

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-testHPV test and LBC both requested and performed on a cervical sample., 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 NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears..

Future research priorities

Currently there is insufficient evidence to determine the most appropriate follow-up for patients who have had AISAdenocarcinoma in situ 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 NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.) 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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References

  1. 1.01.1 Schockaert S, Poppe W, Arbyn M, Verguts T, Verguts J. Incidence of vaginal intraepithelial neoplasia after hysterectomy for cervical intraepithelial neoplasia: a retrospective study. Am J Obstet Gynecol 2008 Aug;199(2):113.e1-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18456229.
  2. Cancer Australia. Vaginal cancer. [homepage on the internet] Sydney: Cancer Australia; 2014 Available from: http://canceraustralia.gov.au/affected-cancer/cancer-types/gynaecological-cancers/vaginal-cancer.
  3. 3.03.13.23.3 Soutter WP, Sasieni P, Panoskaltsis T. Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia. Int J Cancer 2006 Apr 15;118(8):2048-55 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16284947.
  4. 4.04.1 National Health and Medical Research Council. Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen detected abnormalities. Canberra: NHMRCNational Health and Medical Research Council; 2005.
  5. Australian Institute of Health and Welfare. Report on monitoring activities of the National Cervical Screening Program Safety Monitoring Committee. Cancer series 80. Cat. no. CAN 77. Canberra: AIHWAustralian Institute of Health and Welfare; 2013 Available from: http://www.aihw.gov.au/publication-detail/?id=60129545158).
  6. Frega A, French D, Piazze J, Cerekja A, Vetrano G, Moscarini M. Prediction of persistent vaginal intraepithelial neoplasia in previously hysterectomized women by high-risk HPV DNA detection. Cancer Lett 2007 May 8;249(2):235-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17070990.
  7. 7.07.1 Stokes-Lampard H, Wilson S, Waddell C, Ryan A, Holder R, Kehoe S. Vaginal vault smears after hysterectomy for reasons other than malignancy: a systematic review of the literature. BJOG 2006 Dec;113(12):1354-65 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17081187.
  8. Murta EF, Neves Junior MA, Sempionato LR, Costa MC, Maluf PJ. Vaginal intraepithelial neoplasia: clinical-therapeutic analysis of 33 cases. Arch Gynecol Obstet 2005 Oct;272(4):261-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16001196.
  9. Parva M, Nicholas VC, Holtz DO, Bratic AK, Dunton CJ. Posthysterectomy cytology screening: indications and clinical implications. J Low Genit Tract Dis 2012 Jan;16(1):45-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22207152.
  10. Babarinsa I, Mathew J, Wilson C, Oladipo A. Outcome of vaginal intraepithelial neoplasia following hysterectomy for cervical intraepithelial neoplasia. J Obstet Gynaecol 2006 Feb;26(2):157-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16483977.
  11. González Bosquet E, Torres A, Busquets M, Esteva C, Muñoz-Almagro C, Lailla JM. Prognostic factors for the development of vaginal intraepithelial neoplasia. Eur J Gynaecol Oncol 2008;29(1):43-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18386462.
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Appendices

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