Appendix A. Modelled evaluation of the predicted benefits, harms and cost-effectiveness of the renewed National Cervical Screening Program (NCSP) in conjunction with these guideline recommendations

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Contents

Introduction

A modelling approach was used to predict the impact of the renewed 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.), when implemented in conjunction of these guidelines, on benefits, harms, cost-effectiveness and resource utilisation. The estimates presented here are an update of predictions that underpinned the Medical Services Advisory committee (MSACThe Australian Medical Services Advisory Committee) recommendations.[1]

The findings are summarised in Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed NCSP. This appendix briefly describes the modelling methods and details the updates included since the model platform was used for the MSACThe Australian Medical Services Advisory Committee evaluation. Updates affecting the overall effectiveness and costs associated with 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. include changes in:

  • guidelines for the management of women post colposcopy
  • assumptions about compliance with colposcopy
  • end age for screening.

Methods

Model platform

We used the same model platform that was used for the MSACThe Australian Medical Services Advisory Committee evaluation. This platform has been used for a number of human papillomavirus (HPVHuman papillomavirus) vaccination evaluations as well as screening technology, screening interval and screening management evaluations performed on behalf of national cervical screening programs in Australia, New Zealand and England. A schematic of the model is shown in Figure A.1. The model consists of several elements:

  1. a dynamic model of sexual behaviour, HPV transmission and vaccination in females and males based on vaccination uptake rates reported by the National HPV Vaccination Program RegisterA 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.
  2. a multi-HPV-type model of the natural history of HPV infection, progression, regression, the development 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.) and invasive cervical cancer
  3. a model of cervical screening, diagnosis and treatment of 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.
  4. a multiple-cohort implementation which separately models HPV exposure, CIN development, screening, and all downstream processes, for each age cohort of females
  5. a population component that applies demographic data to the outputs to estimate cross-sectional results.


A more detailed description of the model, including data sources, model validation and calibration targets and previous applications of the model, can be found in MSACThe Australian Medical Services Advisory Committee’s NSCP renewal executive summary report.[1]

Figure A.1. Schematic diagram of model structure

Benefits and harms Schematic diagram of model structure.png

This flow diagram represents the natural history assumptions specific to a single HPV type. If multiple HPV infections exist, each will have the same flow dynamics, but the rates of progression and regression occur independently for each HPV type.

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Screening compliance assumptions

When modelling the pre-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., we incorporated data on age-specific screening initiation and compliance with screening and management recommendations in Australian women, informed by an analysis of data obtained from Victoria Cervical Cytology 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. (VCCR). When modelling 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., assumptions were based on the introduction of a call-and-recall system, with women sent invitations at age 25 years. We assumed that the number of women who attend their first screening test at age 25 years (the new initiation age) will be at least equivalent to the number who, under the pre-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., had their first screening test before, or at, the age of 25. For the purposes of this modelled evaluation, we assumed that no screening occurs before the age of 25 years under 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.. Compliance with re-attendance for women in routine screening under 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. was evaluated assuming implementation of the call-and-recall screening organisation system. The behaviour of women under a call-and-recall system was informed by data from England, where such a system has been implemented. While the proportion of women who attend before or at the recommended screening interval (5 years under 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.) is informed by the screening pattern observed in England, we assume that the coverage at 7 years is equivalent to that currently observed under the pre-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. (i.e. that changing the recommended screening interval, by itself, will not change behaviour in very under-screened women). The modelled probability of re-attending, according to the time since last screening test, is shown in Figure A.2. We assumed that, for a given recall timeframe, the probability of attending a follow-up test in 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. is equivalent to that currently observed under the pre-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..

As part of the MSACThe Australian Medical Services Advisory Committee evaluation, we previously explored a range of screening attendance assumptions, including slower screening uptake rates and a less ‘efficient’ call-recall system (in which there was a higher rate of early re-attendance and a lower rate of on-time attendance). Details of the impact of these screening assumptions can be found in MSACThe Australian Medical Services Advisory Committee’s NSCP renewal executive summary report.[1]

Figure A.2. Probability of re-attendance for women in routine screening

Probability of re-attendance for women in routine screening.png

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Changes from the model used for the MSACThe Australian Medical Services Advisory Committee Evaluation (to reflect these draft guidelines)

Updates to the management of women post-colposcopy

We have incorporated into the model the new recommendations in these guidelines for post-colposcopy management. These include recommendations for women who were referred 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, or women under follow-up with a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result, with each of the following colposcopy results (see Colposcopy terminology in Chapter 7. ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities.):

  • i) normal 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.) (negative colposcopy)
  • ii) abnormal 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. and histologically confirmed CIN2 or lesser-grade lesion
  • iii) type 3 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..

We have also incorporated new recommendations, according to these guidelines, for women referred to colposcopy who subsequently received pre-cancer treatment.

Table A.1 summarises updated post-colposcopy management for women referred with a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result and a liquid-based cytology (LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.) report of negative, possible low-grade squamous intraepithelial lesion (pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system.) or low-grade squamous intraepithelial lesion (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.). Table A.2 shows updated post-colposcopy management for women who have an LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction of possible high-grade squamous intraepithelial lesion (pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.) or high-grade squamous intraepithelial lesion (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).). These updates have been incorporated into the model.

Table A.1. Changes in post-colposcopy management for women with an LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of negative, pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system. or 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., based on 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. recommendations

Normal 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. Type 3 TZType 3 TZ: part or the entire upper limit of the TZ cannot be seen in the canal ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. abnormal and biopsy < CIN2 Treated for CIN2+ and under test-of-cure
MSACThe Australian Medical Services Advisory Committee model assumptions* Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

Referral to colposcopy if any positive‡ at 12 months or 24 months
Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

Referral to colposcopy any +ve test‡ at 12 or 24 months
Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

Referral to colposcopy if pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.+ or if both oncogenic HPV +veWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. (any type) and pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system.+

No referral to colposcopy if oncogenic HPV (any type) +ve and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. negative, or oncogenic HPV not detectedOncogenic HPV types not detected by the HPV testing platform. and cytology 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.
Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. if 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.+

Otherwise, continue annual co-testingHPV test and LBC both requested and performed on a cervical sample. until 2 consecutive double negatives
Updated model assumptions HPV testing at 12 months

Referral to colposcopy if oncogenic HPV (16/18) +ve, or oncogenic HPV (non 16/18) +ve with 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.+

Discharge to routine screening if oncogenic HPV not detectedOncogenic HPV types not detected by the HPV testing platform.
HPV testing at 12 and 24 months

Referral to colposcopy if oncogenic HPV +veWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. (any type)at either visit§

Return to routine screening if oncogenic HPV not detectedOncogenic HPV types not detected by the HPV testing platform. at 12 months and 24 months
HPV testing at 12 months

Referral to colposcopy if oncogenic HPV (16/18) +ve, or oncogenic HPV (non 16/18) +ve with 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.+

Discharge to routine screening if oncogenic HPV not detectedOncogenic HPV types not detected by the HPV testing platform.
Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. if cytology pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.+ or oncogenic HPV (16/18) +ve (irrespective of LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.)

Otherwise, continue annual co-testingHPV test and LBC both requested and performed on a cervical sample. until 2 consecutive double negatives
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.: transformation zone

Co-testingHPV test and LBC both requested and performed on a cervical sample.: HPV test and 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.+: possible 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 higher-grade lesion
pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system.+: possible 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. or higher-grade lesion
+ve: positive test result
* Model assumptions used for the MSACThe Australian Medical Services Advisory Committee evaluation (for the base case MSACThe Australian Medical Services Advisory Committee evaluation)
Model assumptions reflecting the updated recommendations in these guidelines
‡ Oncogenic HPV (any type) detected or any abnormality on LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.
§In the model, we assumed that women attending their visit at 24 months would be referred to colposcopy if they 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, but not for 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.

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Table A.2. Changes in post-colposcopy management for women with an LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report of pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system. or 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)., based on 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.

Normal 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. Type 3 TZType 3 TZ: part or the entire upper limit of the TZ cannot be seen in the canal ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. abnormal and biopsy < CIN2 Treated for CIN2+ and under test-of-cure
MSACThe Australian Medical Services Advisory Committee model assumptions* Return for a LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. and colposcopic assessment at 6 and 12 months Cold-knife cone biopsy is recommended. However, women who are concerned about fertility† can have a repeat colposcopy in 4 months. If the 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. is still not visible, diagnostic excision is recommended Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

Referral to colposcopy if pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.+ or if both oncogenic HPV (any type) +ve and pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system.+

No referral to colposcopy if oncogenic HPV (any type) +ve and cytology negative, or oncogenic HPV not detectedOncogenic HPV types not detected by the HPV testing platform. and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. 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.
Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. if 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.+

Otherwise, continue annual co-testingHPV test and LBC both requested and performed on a cervical sample. until 2 consecutive double negatives
Updated model assumptions** Diagnostic excision of the 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. is recommended§

Women who had confirmed pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system. and are concerned about fertility can have a repeat assessment at 6 and 18 months with an HPV and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. co-testHPV test and LBC both requested and performed on a cervical sample.
Diagnostic excision of the 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. is recommended regardless of whether the referring LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. is pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system. or 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).§ Diagnostic excision of the 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. is recommended

Women who had confirmed pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system. and are concerned about fertility can have a repeat assessment at 12 and 24 months with an HPV and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. co-testHPV test and LBC both requested and performed on a cervical sample.
Co-testingHPV test and LBC both requested and performed on a cervical sample. at 12 and 24 months

ColposcopyThe examination of the cervix and vagina with a magnifying instrument called a colposcope, to check for abnormalities. if 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.+ or oncogenic HPV (16/18) +ve (irrespective of LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.)

Otherwise, continue annual co-testingHPV test and LBC both requested and performed on a cervical sample. until 2 consecutive double negatives
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.: Transformation zone

pHSILPossible HSIL in the Australian Modified Bethesda System is broadly equivalent to ASC-H in US Bethesda system.+: possible 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 higher-grade lesion
pLSILPossible LSIL in the Australian Modified Bethesda System is broadly equivalent to ASCUS in US Bethesda system.+: possible 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. or higher-grade lesion
*Model assumptions used for the MSACThe Australian Medical Services Advisory Committee evaluation (for the base case MSACThe Australian Medical Services Advisory Committee evaluation)
** Model assumptions reflecting the updated recommendations in these guidelines
Based on Australian fertility rates for 2011, we have estimated the probability that a woman would have no further births from the age of 35 on as 64%. By age 40, this has increased to 92% and by age 45 it is over 99%. We therefore assume the following for the purposes of this modelled evaluation:
(i) All women aged < 35 years will choose to defer excisional biopsy
(ii) 35% of women aged 35–39 will choose to defer excisional biopsy
(iii) 8% of women aged 40–44 years will choose to defer excisional biopsy
(iv) No women aged 45+ will choose to defer excisional biopsy.
§ We assume all women will undergo diagnostic excision of the transformation zone at this point.
It is assumed that:
(i) women have a co-testHPV test and LBC both requested and performed on a cervical sample. (HPV and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.), along with a colposcopy, at both visits
(ii) a woman undergoes diagnostic excision of the transformation zone if oncogenic HPV (any type) is detected, or oncogenic HPV is not detected and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. prediction is 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)..
(iii) if oncogenic HPV is not detected and cytology is negative at both visits, women are referred to routine screening.

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Updates to colposcopy compliance assumptions

Modelling undertaken for the MSACThe Australian Medical Services Advisory Committee evaluation assumed that compliance with colposcopy referral was dependent on the accompanying cytology result, and was generally higher in women referred with a 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).. This was based on observed data from the Victorian Cervical Cytology RegisterA 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., and is likely due to the fact that, under 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., women referred with a high-grade cytology prediction receive reminder letters and phone calls if they have not attended colposcopy within a certain interval (shorter than the interval for reminders sent for women without a high-grade cytology prediction). We sought advice on whether these assumptions should be revised by considering management protocols for following up women within the primary HPV screening arm of the Compass trial, given that the Compass protocol closely resembles the proposed clinical pathway recommended in this guideline. Based on Compass management, we assumed that:

  • women who are referred for colposcopy (regardless of the reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. result) are followed up in the same way as for women with a 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). cytology under 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.
  • women will attend colposcopy at a rate similar to what is observed in women who test 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). on cytology under 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. program.

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Updates to HPV exit testing assumptions used in modelling

For the MSACThe Australian Medical Services Advisory Committee evaluation, when we provided predictions for women having primary HPV screening, we assumed that exit testing would be offered to women aged 60–64 years, which we described as screening ending at 64 years. As an exploratory analysis, we considered a scenario in which exit HPV testing would be offered to women aged 65–69 years, which we described as screening ending at 69 years. MSACThe Australian Medical Services Advisory Committee has since recommended that women have an exit HPV test between 70 and 74 years of age.

Furthermore, these new guidelines recommend women aged 70–74 years who have an are oncogenic HPV (any type) positive test result at their final screening test be referred directly to colposcopy, regardless of the HPV type or the reflex LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. result. This management process differers from the MSACThe Australian Medical Services Advisory Committee model, which assumed there was no referral to colposcopy for women who had an oncogenic HPV (not 16/18) positive test result but who had a negative LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory. report. Therefore, we updated the model to account for this change in management of women at their final screening visit.

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Results

Note: The model incorporated assumptions about compliance with screening in 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. after taking into account the introduction of a call-and-recall system for screening. The specific assumptions for adherence were described in detail in the MSACThe Australian Medical Services Advisory Committee evaluation[2] and are summarised here (see screening compliance assumptions). The predicted impact of 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., and associated cervical cancer incidence and mortality reductions, are predicated on achieving the level of compliance assumed.

Incremental impact of the changes from the model used for MSACThe Australian Medical Services Advisory Committee

Table A.3 summarises the incremental impact of each change that was made from the model used for the MSACThe Australian Medical Services Advisory Committee evaluation. This was done to determine the relative impact of each change on overall model predictions. Incorporation of the new recommendations in these guidelines for women who were referred to colposcopy with a cytology report of 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. and had a (i) negative colposcopy, (ii) type 3 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. (iii) a histologically confirmed < CIN2 lesion, or (iv) received treatment for CIN2/3, results in a further 3% reduction in cervical cancer incidence and mortality in unvaccinated cohorts and a 1–3% reduction in cohorts offered vaccination, compared with the prior predictions for 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.. The change results in 2% more colposcopies in unvaccinated cohorts and 9% fewer colposcopies in cohorts offered vaccination.

Incorporation of the updated guidelines for women who were referred to colposcopy with a cytology report 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). and had a (i) negative colposcopy, (ii) type 3 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., or (iii) a biopsy-confirmed <CIN2 lesion results in a further 5–6% reduction in cervical cancer incidence and mortality in unvaccinated cohorts and a 4% reduction in cohorts offered vaccination, compared with the prior predictions for 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.. This change has no effect on colposcopies in unvaccinated cohorts but increases colposcopies by a further 2% in cohorts offered vaccination.

Incorporating the changes to the compliance assumptions for women referred to colposcopy results in a further reduction of 2% in cervical cancer incidence and mortality in unvaccinated cohorts and a 1–2% reduction in cohorts offered vaccination, compared with the prior predictions for 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.. The change results in an increase in colposcopy referrals of 7% in unvaccinated cohorts and 5% in cohorts offered vaccination. Incorporating the changes to the screening end-age, we predict a 2–3% reduction in cervical cancer incidence and mortality in both unvaccinated cohorts and cohorts offered vaccination, compared with the prior predictions for 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.. This change results in a 1% increase in colposcopies for both unvaccinated cohorts and cohorts offered vaccination.

As an exploratory analysis, we also evaluated a scenario in which women were not managed differently at their final screening test at ages 70–74, and were instead managed the same way as women who tested HPV positiveWomen with a positive HPV test result of any oncogenic HPV types detected using HPV testing platforms in a pathology laboratory. at younger ages (i.e. we assume that there is no special exit test offered to women at their final screen). In this case, we predict < 0.5% increase in cervical cancer incidence, compared with the scenario in which women are who have a positive oncogenic HPV (any type)Women with a positive HPV test result of any oncogenic HPV types detected using routine HPV testing in a pathology laboratory. test result are referred to colposcopy at their final test when aged 70–74 years. These findings suggest that extending the screening end-age has a substantial impact on effectiveness of the program, but providing different management for women who have an oncogenic HPV (any type) positive test result does not have as great an impact on effectiveness.

A.3. Changes in cervical cancer incidence, mortality and number of colposcopies predicted under the new model assumptions compared with 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.

Unvaccinated cohortsWomen who were not offered HPV vaccination, and who experience no herd immunity effects from the National HPV Vaccination Program. Cohorts offered vaccinationWomen who were part of a cohort who were offered vaccination as pre-adolescents (12-13 years), in the context of the National HPV Vaccination Program as implemented in Australia. Specifically, we modelled a cohort of women born in 1997 who were offered vaccination as 12 year olds in 2009. This is the same cohort that was analysed in the Economic Evaluation of the Renewal report.
Cancer cases Cancer deaths Colposcopies Cancer cases Cancer deaths Colposcopies
MSACThe Australian Medical Services Advisory Committee model* –19% –21% +26% –15% –18% –5%
Updated model –31% –36% +36% –24% –29% –7%
Incremental impact after incorporating each change
Referral 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. and any of:
a) colposcopy result Type 3 TZType 3 TZ: part or the entire upper limit of the TZ cannot be seen in the canal
b) histologically confirmed < CIN2
c) colposcopy negative
d) treated for CIN2/3
–3% –3% 2% –1% –3% –9%
Referral 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). and any of:
a) colposcopy result Type 3 TZType 3 TZ: part or the entire upper limit of the TZ cannot be seen in the canal
b) histologically confirmed < CIN2

c) colposcopy negative

–5% –6% 0% –4% –4% 2%
Updated compliance assumptions –2% –3% 7% –2% –1% 5%
Exit HPV test offered at age 70–74 years (extend end-age by 5 years) –2% –3% 1% –2% –3% 1%
Note: Figures are based on the female Australian population as predicted for 2017. Due to rounding, direct adding of the incremental numbers may not result in the presented final impact number.

* Model assumptions used for the MSACThe Australian Medical Services Advisory Committee evaluation (for the base case MSACThe Australian Medical Services Advisory Committee evaluation)
Model assumptions reflecting the updated recommendations in these guidelines.

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Overall benefits of 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. incorporating these guideline recommendations

The impact of 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. on predicted cervical cancer cases, deaths, colposcopies and treatments for CIN2/3, is shown in Table A.4. Under 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. when these guidelines are incorporated, we predict a 31–36% reduction in cervical cancer cases and death in unvaccinated cohorts, and a 24–29% reduction in cohorts offered vaccination, compared with 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.. This is equivalent to 265 fewer cancer cases and 82 fewer deaths annually in unvaccinated cohorts, and 85 fewer cancer cases and 28 fewer deaths annually in cohorts offered vaccination.

Table A.4. Predicted annual numbers of cervical cancer cases and deaths for 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. and 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. (showing differences in case numbers and relative percentage differences)

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. 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.
If HPV vaccination had not been introduced For cohorts offered vaccination as 12 year olds If HPV vaccination had not been introduced For cohorts offered vaccination as 12 year olds
Cervical cancer cases 850 353 584
(–265; –31%)
267
(–85; –24%)
Cervical cancer deaths 227 94 145
(–82; –36%)
66
(–28; –29%)
Note: Figures are based on female Australian population as predicted for 2017.

We also predict an increase in colposcopies for unvaccinated cohorts, but this increase will not be seen in cohorts offered vaccination. Although there would have been a substantial increase in colposcopies if HPV vaccination had not been introduced, it should be noted that 70% of these additional colposcopies would have occurred in women less than 35 years of age. However, all of these women will have been offered vaccination by 2017, when these new clinical guidelines will be implemented. After taking into account the effect of HPV vaccination, the overall impact of 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. on colposcopy and treatment-related harms is expected to be as good or better, when compared to 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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Costs and cost-effectiveness

Table A.5 shows the estimated cost of the 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. before and after renewal. If HPV vaccination had not been introduced, a 19% reduction in program costs is predicted under 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.. For cohorts offered vaccination, a 26% reduction is predicted under 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.. This is equivalent to a cost saving of $41 million per annum for unvaccinated cohorts and $50 million per annum for vaccinated cohorts. It should be noted that these cost savings may not be fully realised, since they are predicated on the assumption that there will be an overall reduction in GP visits due to a reduced number of screening visits. In practice, however, these screening visits may be replaced by routine visits for other conditions with no obvious reduction in costs to the health system.

Since 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. is predicted to be both cost saving and life–year saving, it is not possible to calculate an incremental cost-effectiveness ratio compared with 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.. Table A.5 shows the disaggregated discounted costs and life–years predicted for 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. and 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..

Table A.5. Predicted annual cost of the program and the predicted discounted costs and effects for 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. and 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. (showing differences in costs and relative percentage differences)

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. 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.
If HPV vaccination had not been introduced For cohorts offered vaccination as 12 year olds If HPV vaccination had not been introduced For cohorts offered vaccination as 12 year olds
Annual cost* of the screening program $223 million $192 million $182 million
(–$41 million; –19%)
$142 million
(–$50 million; –26%)
Discounted costsDiscounted costs represent the total predicted cost associated with cervical cancer screening for the lifetime of a woman, which is discounted by 5% per year after the age of 12 years (the age at which the earlier intervention, vaccination, occurs). $383 $325 $304 $227
Discounted life-years 21.6219 21.6239 21.6229 21.6242
Note: Calculations of the annual cost of the screening program are based on female Australian population as predicted for 2017.

Discounting at 5% per annum starting from 12 years of age.

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Conclusion

After incorporating the management recommendations in these guidelines, 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. is expected to be even more effective than previously estimated for the MSACThe Australian Medical Services Advisory Committee evaluation. After taking into account the impact of vaccination, the effect on colposcopies and treatment rates is expected to be consistent with current levels. 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. is also is predicted to be both cost saving and life–years saving.

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References

  1. 1.01.11.2 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/$File/Executive%20Summary%20notated%2013.6.14.pdf.
  2. Medical Services Advisory Committee. National Cervical Screening Program renewal: executive summary. Report November 2013.MSAC application no. 1276. Assessment report. Canberra: Australian Government Department of Health; 2014 Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/E6A211A6FFC29E2CCA257CED007FB678/$File/Executive%20Summary%20notated%2013.6.14.pdf.
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