Oncogenic HPV types 16 and/or 18

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Women who have a positive oncogenic HPV test result indicating the presence of oncogenic HPV types 16 and/or 18, regardless of the presence of any other oncogenic types, should be managed according to the recommendations in this section.

These guidelines incorporate recommended HPVHuman papillomavirus, cytology and histopathology terminology (see Chapter 3. Terminology).

Background

Cross-sectional and longitudinal follow-up studies have shown that HPV type 16 is associated with a higher cross-sectional and future risk of developing CIN grade 2 or higher (CIN2+) and CIN grade 3 or higher (CIN3+) than other oncogenic HPV types.[1] Worldwide, oncogenic HPV types 16/18 are detected in approximately 70% of cervical cancers.[2] Preliminary results from a recent Australian consecutive case series found that HPV types 16 and 18 were detected in 52.3% and 19.4% of cervical cancers, respectively.[3]

HPV testing without genotyping has a high sensitivity but lower specificity for the detection of CIN2+ compared to cytology,[4] so referral of all HPV-positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. women for colposcopic assessment (especially in unvaccinated populations) would result in a large number of unnecessary colposcopy procedures. However, partial genotyping to detect the highest risk oncogenic HPV types 16/18 can be used to stratify risk after primary HPV screening and thus improve the specificity of the HPV test.

MSACThe Australian Medical Services Advisory Committee undertook systematic reviews and modelling analyses to assess the efficacy and safety of the partial genotyping strategy in which women with 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 are referred to colposcopy, and those with 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 are triaged by LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.. MSACThe Australian Medical Services Advisory Committee compared this and other HPV testing strategies with the cytological screening strategy used in 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..

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Evidence

MSACThe Australian Medical Services Advisory Committee systematic reviews

The details and results of the systematic reviews are described in the MSACThe Australian Medical Services Advisory Committee review of evidence report.[1] No studies were identified that provided adequate evidence of the effect of HPV partial genotyping screening strategies on cervical cancer incidence or cervical cancer mortality rates in either vaccinated or unvaccinated populations.

See the MSAC National Cervical Screening Program renewal: evidence review November 2013.

MSACThe Australian Medical Services Advisory Committee modelling

Given the limited evidence from systematic reviews, MSACThe Australian Medical Services Advisory Committee evaluated partial genotyping strategies in the Australian context using a comprehensive model to synthesise clinical trial evidence identified through systematic reviews and Australian data for screening participation, HPV vaccine uptake by age, and management practices.[4]

The modelling approach, assumptions and options are described in the MSACThe Australian Medical Services Advisory Committee reports.[4][5] The modelling for HPV primary screening with partial genotyping indicated an expected reduction in cancer incidence and mortality of over 20% (if women were screened until age 70 years).

See MSAC outcomes. Application No. 1276 – Renewal of the National Cervical Screening Program.

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Recommendations

MSACThe Australian Medical Services Advisory Committee evidence-based recommendationQuestion mark transparent.png

REC6.2: Women with a positive HPV (16/18) test result
Women with 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 directly for colposcopic assessment, which will be informed by the result of reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory..

Consensus-based recommendation*Question mark transparent.png

REC6.3: Referral to gynaecological oncologist for LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of invasive disease
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 with a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of invasive cancer (squamous, glandular or other) should be referred to a gynaecological oncologist or gynaecological cancer centre for urgent evaluation, ideally within 2 weeks.

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REC6.4: Referral of women with a positive HPV (16/18) test result and unsatisfactory LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.
When reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. is unsatisfactory, but the woman requires colposcopic referral regardless of the LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. result (i.e. when HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory. is detected), then the screening episode should be classified as ‘Higher risk for cervical cancer or precursors’. A cervical sample for LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. should be collected at the time of colposcopy (see Chapter 4. Unsatisfactory cervical screening results).

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REC6.5: Referral of women with a positive HPV (16/18) test result and reflex 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).
Women with 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 and reflex 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). should be referred for colposcopic assessment at the earliest opportunity, ideally within 8 weeks.

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Benefits and harms

When making the recommendation to refer women with 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 directly for colposcopic assessment, MSACThe Australian Medical Services Advisory Committee took into account the benefits and harms and the health system implications of partial genotyping and immediate colposcopy in this group.

Updated modelling, taking into account the recommendations in these guidelines, has informed an assessment of the benefits and harms of partial genotyping. The updated modelling used the same platform as that used for the MSACThe Australian Medical Services Advisory Committee evaluation (POLICY1-Cervix),[5] and took into account 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. screening recommendations and management as specified in these guidelines. The findings are summarised in 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

The referral of women with 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 for colposcopy, regardless of the LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction, is a major change to clinical practice and requires appropriate education and implementation.

Resourcing

When making this recommendation, MSACThe Australian Medical Services Advisory Committee took into account the resourcing issues for partial genotyping and the referral of women with 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 for immediate colposcopy.

Updated modelling, taking into account these detailed Guideline recommendations, and taking into account the reduction in oncogenic HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory. infections due to vaccination in the population, has informed an assessment of the resourcing associated with partial genotyping strategies (see Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed National Cervical Screening Program (NCSP)).

Barriers to implementation

A potential barrier is that GPs may not refer 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 to colposcopy, especially if the reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report is negative. However, the risk of this will be mitigated by the laboratory report to the GP, clearly recommending referral and the registry follow-up protocols with reminder letters as needed.

A second potential barrier is that the woman may not fully understand the need for colposcopy, especially if the reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report is negative, and may fail to attend. RegistryA database of identifiable persons containing defined demographic and health information, established for a specific purpose. In the case of cervical screening or other cancer screening registers, the purpose includes inviting eligible persons for screening, sending reminders when they are overdue for screening, follow up of abnormalities, statistical reporting and research. reminder letters will play an important role in this situation.

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References

  1. 1.01.1 Medical Services Advisory Committee. National Cervical Screening Program renewal: evidence review November 2013.MSAC Application No. 1276. Canberra: Australian Government Department of Health; 2014 Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/E6A211A6FFC29E2CCA257CED007FB678/$File/Review%20of%20Evidence%20notated%2013.06.14.pdf.
  2. Clifford GM, Smith JS, Plummer M, Muñoz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 2003 Jan 13;88(1):63-73 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12556961.
  3. Tabrizi S, Brotherton J, Saville M, et al. The Australian Cervical Cancer Study (ACCTS). Data presented at HPV2015,Lisbon 2015;Abstract 347.
  4. 4.04.14.2 Medical Services Advisory Committee. National Cervical Screening Program renewal: executive summary. Report November 2013.MSAC application no. 1276. Assessment report. Canberra: Australian Government Department of Health; 2014 Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/E6A211A6FFC29E2CCA257CED007FB678/$File/Executive%20Summary%20notated%2013.6.14.pdf.
  5. 5.05.1 Medical Services Advisory Committee. National Cervical Screening Program renewal: effectiveness modelling and economic evaluation in the Australian setting. Report November 2013. MSAC application 1276. Canberra: Australian Government Department of Health; 2014 Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/E6A211A6FFC29E2CCA257CED007FB678/$File/Renewal%20Economic%20Evaluation.pdf.
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