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Cervical cancer screening

Investigation of abnormal vaginal bleeding

GUIDELINE UPDATES - This guideline was last updated 7/1/2022

Background

Abnormal vaginal bleeding includes intermenstrual bleeding, postcoital bleeding, and postmenopausal bleeding. 

Intermenstrual bleeding is defined as vaginal bleeding at any time other than during normal menstruation. Postcoital bleeding is vaginal bleeding after sexual intercourse. Intermenstrual bleeding and postcoital bleeding are not diagnoses; they are symptoms that warrant further assessment.[1] Intermenstrual and postcoital bleeding can be associated with genital tract malignancy and premalignant conditions, as well as other conditions such as polyps, leiomyomas, ovulatory disorders, endometrial disorders, sexually transmitted infections, hormonal contraception and trauma.[2][3] It is understood that most vaginal bleeding actually originates in the uterine body or cervix. 

Current Australian clinical practice guidelines developed by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG)[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, if warranted, referral to a gynaecologist. Heavy menstrual bleeding (HMB) originates in the uterus and is not a symptom of cervical cancer. 

While cancer is an uncommon cause of abnormal vaginal bleeding in women of any age, and is rare in young women, 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 RANZCOG advises that women reporting postcoital bleeding should have a co-test (HPV and LBC) and a test for chlamydia. A single episode of postcoital bleeding in a woman with a normal co-test and normal cervical appearance does not warrant immediate referral for colposcopy but recurrence or persistence of postcoital bleeding mandates referral to a gynaecologist .[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] 

The RANZCOG advises that women at risk of sexually transmitted infections should have appropriate tests performed, and that those with persistent unexplained intermenstrual bleeding should have a co-test (HPV and LBC), transvaginal ultrasound, and referral to a gynaecologist. 

Postmenopausal bleeding always requires investigation and specialist referral to exclude genital tract disease including cervical and endometrial malignancy. The presence of blood has the potential to adversely affect the sensitivity of any of the available tests for human papillomavirus (HPV) and liquid-based cytology (LBC). For this reason co-testing (HPV and LBC on the same sample) is recommended for women with abnormal vaginal bleeding suggestive of cervical cancer, and follow-up should be based on presenting symptoms, clinical evaluation and the test results. 

A co-test cannot be performed on a self-collected vaginal sample. 

See: Cervical screening and women with symptoms that may be associated with cervical cancer.

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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-testing (the combination of HPV testing and LBC) 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

Consensus-based recommendation

REC18.1: Postcoital and intermenstrual bleeding and testing for HPV and LBC 
When women present with postcoital or persistent unexplained intermenstrual bleeding, appropriate investigations including a clinician-collected cervical sample for a co-test, should be performed and not delayed due to the presence of blood. 

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

Consensus-based recommendation
REC18.2: 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 LBC is negative. 
Consensus-based recommendation
REC18.3: Persistent or recurrent post coital bleeding in pre-menopausal women 
Pre-menopausal women with recurrent or persistent postcoital bleeding, even in the presence of a negative co-test, should be referred to a gynaecologist for appropriate assessment, including colposcopy, to exclude genital tract malignancy. 
Practice point
REC18.4: Postcoital bleeding and sexually transmitted
Sexually transmitted infections, including chlamydia infection, should be considered 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*
REC18.5: Symptomatic women with LBC prediction of cervical cancer 
Women with symptoms and a LBC prediction of invasive cervical cancer should be referred to a gynaecological oncologist or gynaecological cancer centre for assessment, ideally within 2 weeks. 
Consensus-based recommendation
REC18.6: Women with intermenstrual bleeding  
Women with persistent unexplained intermenstrual bleeding require appropriate investigation and should be referred for gynaecological assessment, which may or may not include colposcopy. Common benign causes including a sexually transmitted infection or hormonal contraception-related bleeding should be excluded.
Consensus-based recommendation
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 (which may or may not include colposcopy) regardless of test results, to exclude genital tract malignancy.
Consensus-based recommendation

REC18.8 Circumstances that do not require co-testing or referral for colposcopy
The following circumstances do not require co-testing or referral for colposcopy: 

  • Breakthrough or irregular bleeding due to hormonal contraception 
  • Contact bleeding at time of obtaining a routine cervical screening test sample 
  • Heavy regular periods (heavy menstrual bleeding) 
  • Irregular bleeding due to a sexually transmitted infection (STI), eg. chlamydia. 

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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. Investigation and management of sexually transmitted infections in women with postcoital and intermenstrual bleeding will also avoid over-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 for a clinician-collected sample for a co-test ( HPV and LBC) despite the presence of blood requires education for healthcare professionals. 

Resourcing

The use of co-testing is recommended as part of the initial investigation of women presenting with postcoital bleeding and unexplained intermenstrual bleeding This may affect costs and laboratory workloads. Updates to the guidelines in 2019 provided greater clarity on colposcopy referral in order to reduce over-referral for common benign causes including sexually transmitted infections and hormonal contraception-related causes. 

Barriers to implementation

Healthcare professionals may remain concerned by the presence of postcoital bleeding, despite the reassurance of negative findings on co-testing, and may continue to refer women with only one episode of postcoital bleeding and a clinically normal cervix. Over use of the co-test and referral for colposcopy for women whose abnormal bleeding is due to a common benign cause appears to have occurred at the start of the renewed program. Therefore, the ongoing 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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Author(s):

References

  1. 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 Available from: 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22068978.
  4. 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. 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. 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 Available from: 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 Available from: 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23530690.
  10. 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16147736.
  11. Abu J, Davies Q, Ireland D. Should women with postcoital bleeding be referred for colposcopy? J Obstet Gynaecol 2006 Jan;26(1):45-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16390710.
  12. 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18034351.
  13. 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17429668.
  14. 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 Available from: 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 Available from: 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26254856.
  17. 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/597677.
  18. 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9654181.

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