18. Investigation of abnormal vaginal bleeding

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Background

Intermenstrual bleeding is defined as vaginal bleeding at any time other than during normal menstruation or following sexual intercourse. Postcoital bleeding is vaginal bleeding after sexual intercourse. Intermenstrual bleeding and postcoital bleeding are not diagnoses; they are symptoms that warrant further assessment.[1] Abnormal vaginal bleeding can be associated with genital tract malignancy and premalignant conditions, as well as other conditions such as polyps, adenomyosis, leiomyomas, coagulopathies, ovulatory disorders, endometrial disorders and iatrogenic causes.[2][3]

Current Australian clinical practice guidelines developed by the Royal Australian and New Zealand College of Oncologists (RANZCOGThe Royal Australian and New Zealand College of Obstetricians and Gynaecologists)[1] and by Cancer Australia[4][5] recommend that cervical cancer should be excluded in all women with persistent abnormal vaginal bleeding. The aim of these guidelines is to assist healthcare professionals in the management of intermenstrual bleeding or postcoital bleeding, including testing and/or referral to a specialist gynaecologist.

While cancer is an uncommon cause of abnormal vaginal bleeding in women of any age, postcoital bleeding particularly warrants investigation because it may be a symptom of cervical cancer.[1] A systematic review estimated the overall point prevalence of postcoital bleeding in the community at 0.7–9%, based on data from eight studies conducted mainly in Europe.[6] The RANZCOGThe Royal Australian and New Zealand College of Obstetricians and Gynaecologists advises that a single episode of postcoital bleeding in a woman with a normal Pap smear and normal cervical appearance does not warrant immediate referral for colposcopy, but that colposcopic examination is mandatory for recurrent or persistent postcoital bleeding.[1]

Intermenstrual and other irregular bleeding patterns are common, particularly in women using hormonal contraception (combined hormonal contraceptive pill or vaginal ring, progestogen-only pill, progestogen-only injection, implant or intrauterine device), or hormonal treatment.[7]

Australian guidelines developed during the 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.) era recommend that persistent intermenstrual bleeding should be investigated, as needed, including taking a Pap smear, requesting a pelvic ultrasound and referral for assessment by a gynaecologist.[1][4][5] It is understood that most vaginal bleeding actually originates in the uterine body or cervix.

The presence of blood has the potential to adversely affect the sensitivity of any of the available tests for human papillomavirus (HPVHuman papillomavirus) and liquid-based cytology (LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.). For this reason co-testingHPV test and LBC both requested and performed on a cervical sample. is recommended for women with abnormal vaginal bleeding and follow-up should be based on presenting symptoms,clinical evaluation and the test results.

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Evidence

Systematic review evidence

A systematic review was performed to identify studies evaluating the safety and effectiveness of direct referral to colposcopy, compared with HPV testing and cytology, in women with postcoital bleeding, intermenstrual bleeding or heavy menstrual bleeding. No randomised or pseudorandomised controlled trials were found.

The search strategy and inclusion/exclusion criteria are described in detail in the Technical report.

General literature review evidence

In the absence of any direct evidence from the systematic review, a general review of the literature was performed to inform consensus-based recommendations for investigating abnormal vaginal bleeding, in particular postcoital bleeding and intermenstrual bleeding.

No relevant evidence-based clinical practice guidelines based on systematic reviews of evidence were identified. No studies were found that assessed the safety and effectiveness of direct referral to colposcopy, compared with HPV testing and cytology in women with abnormal uterine bleeding.

One systematic review,[6] two prospective cohort studies[8][9] and seven retrospective cohort studies[10][11][12][13][14][15][16] reported outcomes in women with postcoital bleeding, including cytology findings, rates of cervical intraepithelial neoplasia grades 2 and 3 (CIN2, CIN3), invasive cervical carcinoma, and other diagnoses. Outcomes were reported according to known pre-referral cytology status and age group, where available. No studies reported cervical abnormalities according to HPV status in women with postcoital bleeding.

The systematic review[6] included two studies based on data from the Finnish national screening registry and national cancer registry.[17][18] The first study[17] reported outcomes for women tested in 1963–1971 after the introduction of a mass cervical screening program and followed up at the end of 1972. Women with postcoital bleeding and normal referral cytology showed a 15-fold higher risk of developing invasive cervical carcinoma than women without postcoital bleeding.

However, the later study,[18] which reported outcomes in women screened from 1985-–1990 and followed up to 1994, found that postcoital bleeding carried a 3-fold risk of invasive cervical carcinoma in women with normal referral cytology. The reduction in risk associated with postcoital bleeding was presumed to be due to changes in prevalence and incidence of cancer since screening had been introduced.[6] The same systematic review estimated rates of invasive cervical cancer among women with postcoital bleeding (with community populations) to be approximately one in 44,000 for those aged 20–24 years, one in 5600 for those aged 25–34 years, one in 2800 for those aged 35–44 years and one in 2400 for those aged 45–54 years.[6]

In retrospective cohort studies, reported rates of invasive cervical carcinoma diagnosed in women with postcoital bleeding and normal or no referral cytology ranged from nil to 3.6%.[12][13][10] One study reported rates of CIN3 of 2.3% among women with postcoital bleeding and normal cytology who attended colposcopy.[13] Among women with postcoital bleeding and abnormal referral cytology, rates of invasive cervical cancer ranged from nil to 5%.[10][11][14]

We did not identify published studies, and we are unaware of any ongoing studies, directly evaluating the use of HPV testing or co-testingHPV test and LBC both requested and performed on a cervical sample. (the combination of HPV testing and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. in the investigation of postcoital bleeding in women.

A summary of the literature considered can be found in the Technical report.

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Recommendations

Flowchart 18.1. Investigation of women with abnormal vaginal bleeding

Investigation of women with abnormal vag bleeding.PNG



Consensus-based recommendationQuestion mark transparent.png

REC18.1: Women with abnormal vaginal bleeding
Women at any age who have signs or symptoms suggestive of cervical cancer should have a co-testHPV test and LBC both requested and performed on a cervical sample., and referral for appropriate investigation to exclude genital tract malignancy should be considered.

Consensus-based recommendationQuestion mark transparent.png

REC18.2: Abnormal vaginal bleeding and testing for HPV and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.
When women present with abnormal vaginal bleeding, appropriate investigations, which may include a cervical sample for a co-testHPV test and LBC both requested and performed on a cervical sample., should be performed and not delayed due to the presence of blood.

The woman’s recent cervical screening history should also be considered.

Consensus-based recommendationQuestion mark transparent.png

REC18.3: Postcoital bleeding in pre-menopausal women
Pre-menopausal women who have a single episode of postcoital bleeding and a clinically normal cervix do not need to be referred for colposcopy if oncogenic HPV is not detected and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. is negative.

If postcoital bleeding recurs or persists despite a negative co-testHPV test and LBC both requested and performed on a cervical sample. women should be referred to a gynaecologist for appropriate assessment, including colposcopy, to exclude genital tract malignancy.

Practice pointQuestion mark transparent.png

REC18.4: Postcoital bleeding and sexually transmitted infections
Sexually transmitted infections, including Chlamydia infection, should be considered and, when appropriate, excluded in all women presenting with postcoital bleeding. It is necessary to obtain a sexual health history and perform appropriate tests and investigations.

Consensus-based recommendation*Question mark transparent.png

REC18.5: Symptomatic women with LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of cervical cancer
Women with symptoms and a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of invasive cervical cancer should be referred to a gynaecological oncologist or gynaecological cancer centre for assessment.

Consensus-based recommendationQuestion mark transparent.png

REC18.6: Women with intermenstrual bleeding may require specialist referral
Women with persistent and/or unexplained intermenstrual bleeding require appropriate investigation and should be referred for specialist gynaecological assessment, regardless of any test results.

Consensus-based recommendationQuestion mark transparent.png

REC18.7: Postmenopausal women with vaginal bleeding require specialist referral
Postmenopausal women with any vaginal bleeding, including postcoital bleeding, should be referred for a specialist gynaecological assessment, to exclude genital tract malignancy.

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Benefits and harms

While cancer is an uncommon cause of abnormal vaginal bleeding in women of any age, postcoital bleeding in particular warrants investigation because it may be a symptom of cervical cancer. For premenopausal women, with a single episode of postcoital bleeding, these recommendations will limit over-investigation, especially referral for colposcopy.

Overall, these recommendations are conservative, since the majority of women who are investigated will not be found to have serious disease. The reassurance provided by confirmation of disease-free status should be considered a benefit. Given the small but serious risk of underlying invasive cancer, these recommendations are considered to represent the best balance of benefits and harms.

See Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed National Cervical Screening Program (NCSP).

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Health system implications of these recommendations

Clinical practice

Some healthcare professionals are reluctant to perform a cervical examination during bleeding. Therefore, implementation of the recommendation to take a sample for an HPV test and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. despite the presence of blood may require education for healthcare professionals.

Resourcing

The use of co-testingHPV test and LBC both requested and performed on a cervical sample. is recommended as part of the initial investigation of women presenting with abnormal vaginal bleeding. This may have some resourcing implications in regards to costs and laboratory work load. It is not anticipated that this will be of great significance as the suggested management is otherwise unchanged from the previous guidelines.

Barriers to implementation

Healthcare professionals may remain concerned by the presence of postcoital bleeding, despite the reassurance of negative findings on co-testingHPV test and LBC both requested and performed on a cervical sample., and may continue to refer women with only one episode of postcoital bleeding and a clinically normal cervix. Therefore, the education of healthcare professionals is of paramount importance to successful implementation of this recommendation.

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Discussion

Unresolved issues

No unresolved issues have been identified.

Future research priorities

Future research could be carried out using routinely collected data to determine the most appropriate approach to managing younger women with symptoms.

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References

  1. 1.01.11.21.31.4 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Investigation of intermenstrual and postcoital bleeding. Melbourne: RANZCP; 1995 [cited 2015 Mar].
  2. Bahamondes L, Ali M. Recent advances in managing and understanding menstrual disorders. F1000Prime Rep 2015;7:33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25926984.
  3. Munro MG, Critchley HO, Fraser IS. The flexible FIGO classification concept for underlying causes of abnormal uterine bleeding. Semin Reprod Med 2011 Sep;29(5):391-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22068978.
  4. 4.04.1 Cancer Australia National Centre for Gynaecological Cancers. Abnormal vaginal bleeding in pre- and peri-menopausal women.A diagnostic guide for general practitioners and gynaecologists [Chart]. Cancer Australia; 2011 Available from: https://canceraustralia.gov.au/sites/default/files/publications/ncgc-vaginal-bleeding-flowcharts-march-20111_504af02038614.pdf.
  5. 5.05.1 Cancer Australia National Centre for Gynaecological Cancers. Vaginal bleeding in post-menopausal women.A diagnostic guide for general practitioners and gynaecologists [Chart]. Cancer Australia; 2011 Available from: https://canceraustralia.gov.au/sites/default/files/publications/ncgc-vaginal-bleeding-flowcharts-march-20111_504af02038614.pdf.
  6. 6.06.16.26.36.4 Shapley M, Jordan J, Croft PR. A systematic review of postcoital bleeding and risk of cervical cancer. Br J Gen Pract 2006 Jun;56(527):453-60 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16762128.
  7. Faculty of Sexual & Reproductive Healthcare (FSRH). Problematic Bleeding with Hormonal Contraception. England: Faculty of Sexual & Reproductive Healthcare (FSRH); 2015 Available from: http://www.fsrh.org/pdfs/CEUGuidanceProblematicBleedingHormonalContraception.pdf.
  8. Alfhaily F, Ewies AA. Managing women with post-coital bleeding: a prospective observational non-comparative study. J Obstet Gynaecol 2010 Feb;30(2):190-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20143983.
  9. Shapley M, Blagojevic-Bucknall M, Jordan KP, Croft PR. The epidemiology of self-reported intermenstrual and postcoital bleeding in the perimenopausal years. BJOG 2013 Oct;120(11):1348-55 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23530690.
  10. 10.010.110.2 Khattab AF, Ewies AA, Appleby D, Cruickshank DJ. The outcome of referral with postcoital bleeding (PCB). J Obstet Gynaecol 2005 Apr;25(3):279-82 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16147736.
  11. 11.011.1 Abu J, Davies Q, Ireland D. Should women with postcoital bleeding be referred for colposcopy? J Obstet Gynaecol 2006 Jan;26(1):45-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16390710.
  12. 12.012.1 Ray P, Kaul V. Prevalence of high-grade squamous intraepithelial neoplasia (HiSIL) in symptomatic women referred to the colposcopy clinic with negative cytology. Arch Gynecol Obstet 2008 Jun;277(6):501-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18034351.
  13. 13.013.113.2 Sahu B, Latheef R, Aboel Magd S. Prevalence of pathology in women attending colposcopy for postcoital bleeding with negative cytology. Arch Gynecol Obstet 2007 Nov;276(5):471-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17429668.
  14. 14.014.1 Tehranian A, Rezaii N, Mohit M, Eslami B, Arab M, Asgari Z. Evaluation of women presenting with postcoital bleeding by cytology and colposcopy. Int J Gynaecol Obstet 2009 Apr;105(1):18-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19150060.
  15. See AT, Havenga S. Outcomes of women with postcoital bleeding. Int J Gynaecol Obstet 2013 Jan;120(1):88-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23031333.
  16. Gulumser C, Tuncer A, Kuscu E, Ayhan A. Is colposcopic evaluation necessary in all women with postcoital bleeding? Eur J Obstet Gynecol Reprod Biol 2015 Oct;193:83-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26254856.
  17. 17.017.1 Hakama M, Pukkala E. Selective screening for cervical cancer. Experience of the Finnish mass screening system. Br J Prev Soc Med 1977 Dec;31(4):238-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/597677.
  18. 18.018.1 Viikki M, Pukkala E, Hakama M. Bleeding symptoms and subsequent risk of gynecological and other cancers. Acta Obstet Gynecol Scand 1998 May;77(5):564-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9654181.
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Appendices

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