14. Screening in pregnancy

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Background

Cervical screening during pregnancy is a special circumstance, as additional consideration needs to be given for the wellbeing of the foetus. The incidence of cervical cancer in pregnancy is low, with estimates in the literature ranging from 3.3 to 26 cases per 100,000 births.[1][2] However, early-stage cervical cancer may be more frequently encountered by clinicians caring for women during their pregnancy due to higher age-specific incidence rates in the 30–39 year age group, compared with younger ages,[3] and more women delaying pregnancy.[4] Although most cases of cervical abnormalities are likely to be asymptomatic and identified through screening, it is important to consider non-obstetric causes when a pregnant women reports vaginal bleeding (see Chapter 18. Investigation of abnormal vaginal bleeding).[5]

Approximately five per cent of pregnant women will have abnormal cervical cytology.[6] Routine antenatal care should include cervical screening when this is due or overdue. For some women, pregnancy may be the first opportunity for cervical screening and cervical cancer is more likely to be diagnosed in never screened or under-screened women.[3] The tool of choice for collection of a cervical screening specimen in pregnant women should be a broom type brush. The endocervical brush is not recommended.

Conservative management of high-grade squamous intraepithelial lesions (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 recommended during pregnancy.[7] ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. is performed to exclude the presence of invasive cervical cancer, to confirm the presence of pre-invasive disease and reassure the pregnant woman that it is safe to continue with her pregnancy. When 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 diagnosed during pregnancy, treatment can be delayed until after delivery[8] because progression of 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.) to invasive disease during pregnancy is rare, with a range of 0–3% of cases.[9][10][11][8][12] Almost all cases are microinvasive and amenable to curative treatment.

Postpartum regression of CIN lesions is common.[10][13][14] A meta-analysis of studies found that women treated for CIN during pregnancy were at an increased risk of preterm birth (< 37 weeks) and premature rupture of membranes, compared with women with untreated CIN who gave birth before treatment.[15] However, when invasive disease is suspected or confirmed in pregnancy, expert management by a gynaecologic oncologist is required due to the increased risk of poor pregnancy outcomes.

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Evidence

General literature review evidence

A general literature search was conducted to identify recent studies reporting on the natural history of cervical dysplasia during pregnancy and its management.

The available evidence consists of only small studies, with somewhat diverse findings for the natural history of progression and regression of 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). or 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). identified during pregnancy.[10][11][16][17][13][14][18][19] Microinvasive or invasive disease was identified in a small number of cases, most of which were diagnosed post partum.[10][11][16][12][19]

There is evidence to support the safety of colposcopy[10][8][13][14] and biopsy[16] during pregnancy. BiopsyRemoval of tissue for medical examination. of the cervix in pregnancy is associated with a small risk of excessive bleeding from the cervical biopsy site, but is considered otherwise safe.[16][12][10]

The findings are summarised in the Technical report.

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Recommendations

Flowchart 14.1. Management of a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of 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 pregnancy

Mx of LBC prediction of HSIL in pregnancy.PNG






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REC14.1: Positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory.Women with a positive HPV test result of other oncogenic HPV types not including types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. negative or pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./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. in pregnancy
Pregnant women who have a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of negative or prediction of pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system./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. should have a repeat HPV test in 12 months.

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REC14.2: Positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory.Women with a positive HPV test result of other oncogenic HPV types not including types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./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). or any glandular abnormality in pregnancy
Pregnant women who have a positive oncogenic HPV (not 16/18)Women with a positive HPV test result of other oncogenic HPV types other than types 16 and 18 detected using routine HPV testing in a pathology laboratory. test result with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system./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). or any glandular abnormality should be referred for early colposcopic assessment.

When practical and not deferred until the postpartum period.

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REC14.3: Positive HPV (16/18) test result in pregnancy
Pregnant women who have a positive oncogenic HPV (16/18)Women with a positive HPV test result of HPV types 16 and/or 18 detected using routine HPV testing in a pathology laboratory. test result should be referred for early colposcopic assessment regardless of their LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. test result.

When practical and not deferred until the postpartum period.

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REC14.4: Referral of pregnant women with invasive disease
Pregnant women should be referred and seen within 2 weeks by a gynaecological oncologist/gynaecological cancer centre for multidisciplinary team review and management in the following situations:

  • LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of invasive disease
  • colposcopic impression of invasive or superficially invasive squamous cell carcinoma of the cervix
  • histologically confirmed diagnosis of invasive or superficially invasive squamous cell carcinoma of the cervix.
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REC14.5: ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. during pregnancy
The aim of colposcopy in pregnant women is to exclude the presence of invasive cancer and to reassure them that their pregnancy will not be affected by the presence of an abnormal cervical screening test result.

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REC14.6: ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. during pregnancy
ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. during pregnancy should be undertaken by a colposcopist experienced in assessing women during pregnancy.

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REC14.7: Cervical biopsy in pregnancy is usually unnecessary
BiopsyRemoval of tissue for medical examination. of the cervix is usually unnecessary in pregnancy, unless invasive disease is suspected on colposcopy or reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. predicts invasive disease.

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REC14.8: Defer treatment until after pregnancy
Definitive treatment of a suspected high-grade lesion, except invasive cancer, may be safely deferred until after the pregnancy.

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REC14.9: Follow-up assessment after pregnancy
If postpartum follow-up assessment (colposcopy and/or HPV test and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. if necessary) is required, it should be done no less than 6 weeks after delivery and preferably at 3 months. This interval is optimal to reduce the risk of reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. interpretation difficulties or unsatisfactory reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory..

The cervical sample (for HPV test and reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. if necessary) could be collected at the time of postpartum check or at the time of the colposcopic assessment.

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REC14.10: Vaginal oestrogen prior to postpartum colposcopy
For women who are breastfeeding, the use of intra-vaginal oestrogen cream or pessary prior to colposcopy may improve visualisation of the cervix and the quality of any cervical sample for LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory..

Daily for two weeks and cease approximately 3 days before colposcopy.

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REC14.11: Cervical screening in pregnancy
Routine antenatal and postpartum care should include a review of the woman’s cervical screening history. Women who are due or overdue for screening should be screened.

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REC14.12: Cervical screening in pregnancy
A woman can be safely screened at any time during pregnancy, provided that the correct sampling equipment is used. A cytobrush or combi-brush should not be inserted into the cervical canal because of the risk of associated bleeding, which may distress women.

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REC14.13: Self-collection in pregnancy
Self-collection for HPV testing is not recommended in pregnancy.


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Benefits and harms

BiopsyRemoval of tissue for medical examination. is not recommended in pregnancy but may be required, especially when there is suspicion of invasive disease. There is evidence that it is safe to biopsy the cervix during pregnancy, although there may be a risk of excess bleeding.[16][12][10] However, the risk of an undiagnosed cervical cancer in pregnancy outweighs the risk of bleeding from a biopsy.

Deferring treatment of pre-invasive high grade lesions during pregnancy will prevent possible complications of pregnancy loss and excessive bleeding. There is a small risk of progression to invasive cervical cancer during pregnancy, although an Australian case series showed no cases of progression.[20] Most commonly, this will be microinvasive disease, rather than a clinically apparent cancer.

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


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Health system implications of these recommendations

Clinical practice

The recommendations are consistent with current clinical practice. However changes to the cervix in pregnancy make colposcopic assessment more challenging. Although the squamocolumnar junctionThis is the junction where the ectocervical squamous epithelium and the endocervical columnar epithelium meet, and may be located on the visible ectocervix or may be within the endocervical canal. and 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.) are more exposed during pregnancy, complete visualisation of all four quadrants of the cervix is often hindered by oedema, cyanosis, vaginal wall protrusion and thick mucus production.[9] Although colposcopy is safe to perform during pregnancy, an experienced colposcopist should perform the examination owing to the difficulty in differentiating between changes occurring as a result of pregnancy and those due to cervical pathology. A lack of experience could potentially lead to an overestimation of the severity of dysplasia, a mistaken diagnosis of invasive disease and unnecessary investigation during pregnancy.[21]

Resourcing

No additional costs are anticipated.

Barriers to implementation

None.

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Figure 12.1. Collection tools for cervical screening in pregnant women

Figure 12.1.1. Cyto-broom: recommended for use in pregnant women to collect a cervical screening specimen

Cyto-broom for use in pregnant women for collection of a cervical screening specimen

Image source: Victorian Cytology Services Limited.


Figure 12.1.2. Endocervical brush: not recommended for use

Endocervical brush NOT recommended for use in pregnant women for collection of a cervical screening specimen

Image source: Victorian Cytology Services Limited.

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References

  1. Al-Halal H, Kezouh A, Abenhaim HA. Incidence and obstetrical outcomes of cervical intraepithelial neoplasia and cervical cancer in pregnancy: a population-based study on 8.8 million births. Arch Gynecol Obstet 2013 Feb;287(2):245-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23053308.
  2. Pereg D, Koren G, Lishner M. Cancer in pregnancy: gaps, challenges and solutions. Cancer Treat Rev 2008 Jun;34(4):302-12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18291591.
  3. 3.03.1 Australian Institute of Health and Welfare. ACIM (Australian Cancer Incidence and Mortality) reports. Cervical Cancer. Canberra: AIHWAustralian Institute of Health and Welfare; 2015 Available from: http://www.aihw.gov.au/acim-books.
  4. Nguyen C, Montz FJ, Bristow RE. Management of stage I cervical cancer in pregnancy. Obstet Gynecol Surv 2000 Oct;55(10):633-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11023204.
  5. Kärrberg C, Rådberg T, Holmberg E, Norström A. Support for down-staging of pregnancy-associated cervical cancer. Acta Obstet Gynecol Scand 2015 Jun;94(6):654-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25845736.
  6. Blomfield P. Cervical neoplasia in pregnancy. Cancer 2012;14(1):34-5.
  7. 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.
  8. 8.08.18.2 Guijon F. Colposcopy in pregnancy analysis of 1182 patients with abnormal cervical cytology. J Low Genit Tract Dis 2010;14(3):260-61.
  9. 9.09.1 Origoni M, Salvatore S, Perino A, Cucinella G, Candiani M. Cervical Intraepithelial Neoplasia (CIN) in pregnancy: the state of the art. Eur Rev Med Pharmacol Sci 2014;18(6):851-60 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24706310.
  10. 10.010.110.210.310.410.510.6 Wu YM, Wang T, He Y, Song F, Wang Y, Zhu L, et al. Clinical management of cervical intraepithelial neoplasia in pregnant and postpartum women. Arch Gynecol Obstet 2014 May;289(5):1071-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24196304.
  11. 11.011.111.2 Coppolillo EF, DE Ruda Vega HM, Brizuela J, Eliseth MC, Barata A, Perazzi BE. High-grade cervical neoplasia during pregnancy: diagnosis, management and postpartum findings. Acta Obstet Gynecol Scand 2013 Mar;92(3):293-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22880637.
  12. 12.012.112.212.3 Siddiq TS, Twigg JP, Hammond RH. Assessing the accuracy of colposcopy at predicting the outcome of abnormal cytology in pregnancy. Eur J Obstet Gynecol Reprod Biol 2006 Jan 1;124(1):93-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16029922.
  13. 13.013.113.2 Fader AN, Alward EK, Niederhauser A, Chirico C, Lesnock JL, Zwiesler DJ, et al. Cervical dysplasia in pregnancy: a multi-institutional evaluation. Am J Obstet Gynecol 2010 Aug;203(2):113.e1-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20522409.
  14. 14.014.114.2 Serati M, Uccella S, Laterza RM, Salvatore S, Beretta P, Riva C, et al. Natural history of cervical intraepithelial neoplasia during pregnancy. Acta Obstet Gynecol Scand 2008;87(12):1296-300 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18951206.
  15. Danhof NA, Kamphuis EI, Limpens J, van Lonkhuijzen LR, Pajkrt E, Mol BW. The risk of preterm birth of treated versus untreated cervical intraepithelial neoplasia (CIN): a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2015 May;188:24-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25770844.
  16. 16.016.116.216.316.4 Kärrberg C, Brännström M, Strander B, Ladfors L, Rådberg T. Colposcopically directed cervical biopsy during pregnancy; minor surgical and obstetrical complications and high rates of persistence and regression. Acta Obstet Gynecol Scand 2013 Jun;92(6):692-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23590574.
  17. Cubo-Abert M, Centeno-Mediavilla C, Franco-Zabala P, Merced-Vázquez C, Castellví J, García A, et al. Risk factors for progression or persistence of squamous intraepithelial lesions diagnosed during pregnancy. J Low Genit Tract Dis 2012 Jan;16(1):34-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22126830.
  18. Frega A, Scirpa P, Corosu R, Verrico M, Scarciglia ML, Primieri MR, et al. Clinical management and follow-up of squamous intraepithelial cervical lesions during pregnancy and postpartum. Anticancer Res 2007 Jul;27(4C):2743-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17695441.
  19. 19.019.1 Kaplan KJ, Dainty LA, Dolinsky B, Rose GS, Carlson J, McHale M, et al. Prognosis and recurrence risk for patients with cervical squamous intraepithelial lesions diagnosed during pregnancy. Cancer 2004 Aug 25;102(4):228-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15368314.
  20. Woodrow N, Permezel M, Butterfield L, Rome R, Tan J, Quinn M. Abnormal cervical cytology in pregnancy: experience of 811 cases. Aust N Z J Obstet Gynaecol 1998 May;38(2):161-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9653851.
  21. Freeman-Wang T, Walker P. Colposcopy in special circumstances: Pregnancy, immunocompromise, including HIV and transplants, adolescence and menopause. Best Pract Res Clin Obstet Gynaecol 2011 Oct;25(5):653-65 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21843974.
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Appendices

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