Australian Government Department of Health and Ageing
National Cervical Screening Program
Photos of Women

The new NHMRC guidelines for the management of abnormal pap smears in asymptomatic Australian women

Key Points:

  • New terminology system for Pap smear cytology (AMBS2004)
  • Repeat Pap smear for most women with low grade squamous change
  • Do not treat women with biopsy proven CIN 1
  • Refer all women with atypical glandular cell reports for colposcopy
  • Use HPV testing as test of cure following treatment for CIN 2 & CIN 3
In 2001 a multidisciplinary committee chaired by Professor Ian Hammond was convened to review the NHMRC (1994) guidelines for the management of asymptomatic women with screen detected abnormalities on a Pap smear. The Guideline Review Group (GRG) identified several key areas for consideration and a detailed literature review was commissioned in addition to two outcomes studies involving data collected by Australian Pap Test registers. It was recognized that there was new knowledge available regarding the natural history of HPV infection and the role of this agent in cervical carcinogenesis.

NHMRC’s rigorous guideline development process was carefully followed. This involved consultation with all relevant professional bodies and a wide range of clinicians and consumers. These guidelines are an evidence based population health package for Australian women in the context of the National Cervical Screening Program. The NHMRC council approved the new guidelines on 9 June 2005.

There are six major changes in the new guidelines and these are detailed below.

Terminology: the Australian Modified Bethesda System 2004 (AMBS2004).

The need for new terminology arose from two concerns. First there was a need to move away from terminology that suggests an inevitable progression from CIN 1 through to CIN2 and 3 and to cancer. Such progression is now recognized to be a rare event. CIN 1 reflects an infective process and progression to more significant disease is related to persistent infection over many years. The second concern was to provide terminology that was compatible with other systems allowing international research data to be relevant to Australia. The new terminology relates to cytology (Table 1). The CIN terminology will be retained to describe histological diagnoses.

Table 1 The Australian Modified Bethesda System 2004, comparison with previous terminology
New Australian NHMRC terminology

AMBS 2004

Australian NHMRC endorsed terminology 1994
Incorporates
Squamous abnormalities
Possible low-grade squamous intraepithelial lesionLow-grade epithelial abnormalityNonspecific minor squamous cell changes. Changes that suggest but fall short of HPV/CIN 1
Low-grade squamous intraepithelial lesionLow-grade epithelial abnormalityHPV effect, CIN 1
Possible high-grade squamous lesionInconclusive, possible high-grade squamous abnormalityChanges that suggest, but fall short of, CIN 2, CIN 3, or SCC
High-grade squamous intraepithelial lesionHigh-grade epithelial abnormalityCIN 2, CIN 3
Squamous cell carcinomaHigh-grade epithelial abnormalitySquamous cell carcinoma.
Glandular abnormalities
Atypical endocervical cells of undetermined significanceLow-grade epithelial abnormalityNonspecific minor cell changes in endocervical cells.
Atypical glandular cells of undetermined significanceLow-grade epithelial abnormalityNonspecific minor cell changes in glandular cells
Possible high-grade glandular lesionInconclusive, possible high-grade glandular abnormalityChanges that suggest, but fall short of, AIS or adenocarcinoma
AdenocarcinomaHigh-grade epithelial abnormalityAdenocarcinoma

Repeat Pap smear for most women with low grade squamous abnormalities

The new terminology recognizes two categories of low grade squamous intraepithelial lesions (LSIL)
  • possible LSIL, previously known as non specific minor changes; and
  • LSIL, previously know as CIN1 and HPV.
These low grade reports are very common, with approximately 100,000 each year in Australia. This arises because young Australian women (<25yrs) are screened and the two yearly screening interval in Australia results in the increased detection of transient abnormalities. Outcome data from Australian Pap test registers was used to underpin the final recommendations for the management of Australian women with these low grade abnormalities.

These data and information from natural history studies on HPV infection support a delay in the timing of colposcopic assessment, to allow spontaneous resolution of the HPV infection. It is recommended that women with LSIL or possible LSIL should have a repeat Pap test in 12 months. Women who are over 30 years and who do not have the reassurance of a negative Pap test report in the preceding two to three years should be offered immediate colposcopy or a repeat test in six months, or immediate colposcopy.

The new low grade recommendations are safe for Australian women. The GRG constructed a model that estimated no extra cervical cancers would arise as a result of these recommendations and this view was endorsed by a meeting of independent Australian epidemiologists held in November 2004.

Interestingly, there is no international consensus as to how women with low grade abnormalities should be managed. Due to the short two year screening interval in Australia, women with low grade abnormalities will be referred for colposcopy at the same time or earlier than women in other countries with an organised screening program (Table 2).

Table 2 International comparison of suggested management of women with low grade squamous cytologic abnormalities and screening intervals.
Country
Screening Interval

(years)

Cytology
Recommended Management
Finland
5
Pap 2 (atypical cells but no evidence of malignancy) Not referred for further examination unless repeat cytology or other results are suggestive of malignancy.
Australia
2
Low-grade

(possible LSIL and LSIL)

Repeat cytology in 12 months.
Canada
3
ASCUS & LSILRepeat cytology in 6 months.
New Zealand
3
ASCUS & LSILRepeat cytology in 6 months.
Netherlands
5
Pap 2 & 3a1 & 3a2 Repeat cytology in 6 months.
France
3
ASC-US

    LSIL    		Repeat cytology or colposcopy or HPV testing.

    Repeat cytology at 4-6 months or colposcopy.

    USA
    3*
    		ASC-US

      LSIL      		Repeat cytology or colposcopy or HPV testing.

      Colposcopy

      United Kingdom
      3 & 5
      		Borderline change

      Mild dyskaryosis

      		Colposcopy after 3 tests.

      Ideally colposcopy but repeat cytology acceptable.


      * Over 30 years of age and after 3 negative tests

      Do not treat women with biopsy proven CIN1 or HPV lesions

      The previous guidelines were equivocal regarding treatment for biopsy proven low grade lesions. Evidence does not support treatment of these lesions which are likely to spontaneously resolve. The new guidelines recommend that treatment of biopsy proven CIN 1 and HPV should not be undertaken. Treatment is reserved for women who have or subsequently develop a high grade epithelial abnormality.

      Refer all women with atypical glandular cells for colposcopy

      In contrast to low grade squamous epithelial abnormalities, women who have atypical glandular cells of undetermined significance, or indeed any glandular cytologic abnormality, are recommended for colposcopic assessment by a colposcopist with expertise in the colposcopic evaluation of suspected malignancies or by a gynaecological oncologist. Colposcopic assessment of these lesions is notoriously difficult and there has been no impact on the incidence of glandular cancers of the cervix since screening has commenced. There are only 800 women with low grade glandular reports each year in Australia and the higher rate of invasive cancer diagnosis within two years of such a report justified this recommendation.

      Use HPV & cytology as a test of cure for women treated for CIN 2 and 3

      Women who test negative for high risk HPV subtypes following treatment for CIN 2 or 3 have a very low risk of further high grade cervical abnormality. Because the prevalence of HPV positivity falls quite sharply during the first year post treatment, it is recommended that HPV testing is introduced at 12 and 24 months (after treatment) in conjunction with cytology. Once a women has tested negative by both tests on two consecutive occasions, it is recommended that she return to the normal screening interval rather than annual cytology.

      Do not report normal endometrial cells in post menopausal women

      Laboratories currently report the presence of normal endometrial cells found in the Pap smear of women over the age of 45 years. Reporting of this finding is no longer recommended in asymptomatic women because of the very low incidence of endometrial cancer (0.2%).

      We anticipate that these new guidelines will inform gyaecologists and general practitioners in their care of women with screen detected abnormalities. We encourage all of our colleagues and trainees to read this document which details the evidence and recommendations for the optimal care of Australian women who have an abnormal Pap smear. It is available at http://www.nhmrc.gov.au/publications/synopses/wh39syn.htm.

      Penny Blomfield, Margaret Davy, Ian Hammond & Gerry Wain
      Fellows of the RANZCOG and Members of the Guideline Review Group.

      Reproduced with the permission of RANZCOG from O & G Vol 7, No 3, Spring 2005 (with minor changes).

      Page currency, Latest update: 24 April, 2008