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Cervical cancer screening

5. Benefits, harms and cost-effectiveness in renewed National Cervical Screening Program (NCSP)

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

Introduction

All screening programs involve the balancing of benefits, potential harms and cost-effectiveness considerations. 

The benefits of cervical screening include the early detection and treatment of cervical abnormalities, and a reduction in the incidence of invasive cervical cancer and associated mortality. 

Potential harms include the psychosocial impact of receiving an abnormal screening result and being referred for subsequent colposcopy and treatment. Treatment of the cervix may be unnecessary for some lesions that would have regressed without treatment. There is some evidence to suggest that treatment may adversely affect obstetric outcomes in a small proportion of women.[1][2] 

Assessment of the utilisation of health resources considers the impact of cervical screening on clinical services, including colposcopy and treatment. Assessment of the cost-effectiveness of cervical screening considers the total costs of the program and also the benefits in terms of life–years saved in relation to the total costs involved in screening, management of detected abnormalities, and treatment for invasive cervical cancer.

Methods for predicting benefits, harms and cost-effectiveness

A modelling approach was used to predict the impact on the benefits, harms, cost-effectiveness and resource utilisation for the renewed National Cervical Screening Program (NCSP) in conjunction with these guidelines (see 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). The estimates presented here are an update of predictions that underpinned the Medical Services Advisory Committee (MSAC) recommendations,[2] revised to take into account the specific recommendations of this guideline. 

We have used the same model platform that was used for the MSAC evaluation. This platform has been used for a number of HPV 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. Details of the modelling methods, and the updates to model pathways that were made in order to take into account these guideline recommendations, are provided in the Technical report.

The model incorporated assumptions about adherence to screening in the renewed NCSP 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 MSAC evaluation and are summarised in the Technical report. The predicted impact of the renewed NCSP, and associated cervical cancer incidence and mortality reductions, are predicated on achieving the level of adherence assumed

Benefits

The impact of the renewed NCSP on predicted cervical cancer cases, deaths, colposcopies and treatments for cervical intraepithelial neoplasia (CIN) grades 2–3 (CIN2/3) is shown in Table 5.1. Taking into account the recommendations of these guidelines , the model predicts the following outcomes of the renewed NCSP:

  • For unvaccinated cohorts (i.e. assuming vaccination had not been introduced) the model predicts a 31% reduction in cervical cancer incidence and a 36% reduction in cervical cancer mortality, compared with the pre-renewal NCSP – equivalent to 265 fewer cancer cases and 82 fewer cancer deaths annually.
  • For cohorts offered HPV vaccination as 12-year-olds the model predicts a 24% reduction in cervical cancer incidence and a 29% reduction in cervical cancer mortality, compared with the pre-renewal NCSP – equivalent to 85 fewer cancer cases and 28 fewer deaths annually.

See also: 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.

Table 5.1. Predicted annual numbers of cervical cancer cases and deaths for the pre-renewal NCSP and the renewed NCSP (showing differences in case numbers and relative percentage differences)*


Pre-renewal NCSP
Renewed NCSP

If HPV vaccination had not been introducedFor cohorts offered vaccination as 12 year oldsIf HPV vaccination had not been introducedFor cohorts offered vaccination as 12 year olds
Cervical cancer cases850353584
(-265; -31%)
267
(–85; –24%)
Cervical cancer deaths22794145
(-82; -36%)
66
(–28; –29%)

Note: Figures are based on* the female Australian population as predicted for 2017.

Potential harms

Model predictions for impact on colposcopies and treatments

The impact of the renewed NCSP on colposcopies and treatments predicted by the model is shown in Table 5.2. Compared with the pre-renewal NCSP, a 36% increase in colposcopies is predicted if HPV vaccination had not been introduced, but a 7% decrease in colposcopies is predicted in cohorts offered vaccination as 12-year-olds. 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. 

Similarly, a 6% increase in treatments is predicted for CIN2/3 in cohorts not offered HPV vaccination, but a 5% decrease in treatments is predicted for CIN2/3 in cohorts offered vaccination.

For cohorts offered HPV vaccination, overall outcomes for colposcopy and treatment-related harms under the renewed NCSP are expected to be as good or better than for cohorts offered vaccination but managed under the pre-renewal NCSP.

See also: 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.

Table 5.2. Predicted annual numbers of colposcopies and treatments for CIN2/3 for the pre-renewal NCSP and the renewed NCSP (showing differences in case numbers and relative percentage differences)*


Pre-renewal NCSP
Renewed NCSP

If HPV vaccination had not been introducedFor cohorts offered vaccination as 12 year oldsIf HPV vaccination had not been introducedFor cohorts offered vaccination as 12 year olds
Colposcopies85,79560,995116,889
(+31,094; +36%)
56,479
(–4,516; –7%)
Treatments for CIN2/322,66113,89923,963
(+1,302; +6%)
13,240
(–659; –5%)

Note: *Figures are based on the female Australian population as predicted for 2017.

Potential fertility and early pregnancy outcomes

It has been suggested that treatment for CIN2/3 could adversely affect fertility by causing cervical stenosis and a decreased volume of mucus due to the destruction of endocervical glands.[3][4] A systematic review of the literature identified only a few studies, mostly of small size, investigating fertility outcomes in treated women.[5] Based on a pooled analysis of four studies, the overall pregnancy rate in treated women was reported to be higher than in untreated women although significant heterogeneity was observed between the primary studies.[5] A Finnish study investigating the use of in-vitro fertilisation (IVF) among women who had undergone treatment for CIN found that the rate of IVF deliveries was not increased after cervical conisation or ablation.[6] A meta-analysis of studies also reported that treatment did not affect the proportion of women who needed more than 12 months to conceive.[5] 

A meta-analysis also found no effect of treatment on overall rates of miscarriage or of miscarriage during the first trimester.[5] The risk of miscarriage in the second trimester was found to be higher in treated women, compared with untreated women, with the pooled estimate driven primarily by one large study.[7] However, the design of these studies cannot establish a causal link between treatment and second trimester miscarriage, because other factors cannot be excluded.[8]

Potential obstetric complications

Treatment for cervical abnormalities has been associated with subsequent obstetric complications in some studies. A 2006 meta-analysis of observational studies found significantly increased risks of preterm delivery (< 37 weeks), low birth weight (< 2500 g) and preterm premature rupture of membranes among treated women, compared with untreated women.[9] A subsequent meta-analysis reported that cold-knife cone biopsy and ablation by radical diathermy were associated with significantly higher risks of perinatal mortality, severe preterm delivery (< 32/34 weeks) and extreme preterm delivery (< 28/30 weeks), unlike other therapies.[10] The effects of treatment on preterm delivery have been confirmed by some,[11][12][7] but not all[13][14] subsequent studies. A recent study in England reported an increased risk of preterm delivery among first, second and subsequent births with increasing depth of excision (when compared with small excisions of less than 10 mm).[15] 

While the evidence generally suggests an increased risk of obstetric complications following treatment, some evidence suggests that this depends on the depth of excision and amount of cervical tissue removed. Potential confounding factors must also be considered, since even in women with untreated CIN2/3 the risk of preterm delivery may be elevated (possibly due to the presence of risk factors in this group of women that are directly associated with preterm delivery).[14][16][17]

Psychosocial effects

The psychosocial aspects of cervical screening and clinical management of detected abnormalities in the renewed NCSP are discussed in Chapter 19. Psychosocial issues.

Cost-effectiveness

Table 5.3 shows the estimated cost of the NCSP before and after renewal. If HPV vaccination had not been introduced, a 19% reduction in program costs would have been predicted under the renewed NCSP. For cohorts offered vaccination, a 26% reduction in costs is predicted under the renewed NCSP. This is equivalent to a cost saving of $41 million per annum for unvaccinated cohorts and $50 million per annum for cohorts offered vaccination. 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. However, in practice 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 NCSP 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 NCSP. Table 5.3 shows the disaggregated discounted costs and life–years predicted for the pre-renewed NCSP and the renewed NCSP.

See also: 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.

Table 5.3. Predicted annual cost of the program and the predicted discounted costs and effects for the pre-renewed NCSP and the renewed NCSP (showing differences in costs and relative percentage differences)*


Pre-renewal NCSP
Renewed NCSP

If HPV vaccination had not been introducedFor cohorts offered vaccination as 12 year oldsIf HPV vaccination had not been introducedFor 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 costs^$383$325$304$227
Discounted life-years^21.621921.623921.622921.6242

Note: Figures are based on* the female Australian population as predicted for 2017. ^Discounting at 5% per annum starting from 12 years of age.

Impact on clinical practice

The rate of detection of CIN grade 2 and higher (CIN2+) lesions has been reported to increase initially after the transition from cytology-based screening to HPV test-based screening.[18] Accordingly, a transient increase in detected CIN2+ lesions is expected in Australia after the introduction of HPV screening. This may lead to a transient parallel increase in treatments. 

This increase would be offset later by a lower rate of detection of CIN grade 3 and higher (CIN3+), due to increased detection and treatment of lower-grade lesions.[19] Direct referral to colposcopy due to a positive oncogenic HPV (16/18) test result is not expected to result in high colposcopy referral rates among Australian women, due to high uptake of HPV 16/18 vaccination in cohorts born in 1981 or later following the National HPV Vaccination Program, which commenced in April 2007.[20] Overall, colposcopy referrals are expected to fall markedly as the rate of HPV 16/18 infection declines over time. 

To minimise potential harms, MSAC recommended that use of the HPV test is limited to use in healthcare settings that can provide patient counselling, clinical interpretation of results, patient follow-up and confirmatory testing for positive results when required, in addition to testing in a safe environment with infection control procedures.[20] This is important for all women, especially for those who choose to self-collect HPV test samples (see Self-collected samples in Chapter 6. Management of HPV test results). 

Colposcopic assessment and management will be more challenging in the renewed NCSP because there will be a higher proportion of women with a positive oncogenic HPV test result but minimal or no cytological changes.

Barriers to implementation

Education for primary care health professionals and the public will be necessary to support implementation of the renewed NCSP and these clinical management guidelines. It is essential that health professionals have an understanding of the purpose, strategy, benefits and safety of primary HPV screening. If this is not achieved, there may be some resistance to full implementation of these changes.

Author(s):

References

  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/$File/Review%20of%20Evidence%20notated%2013.06.14.pdf.
  2. Medical Services Advisory Committee. National Cervical Screening Program renewal: effectiveness modelling and economic evaluation in the Australian setting. Report November 2013. MSAC application 1276. Canberra: Australian Government Department of Health; 2014 Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/E6A211A6FFC29E2CCA257CED007FB678/$File/Renewal%20Economic%20Evaluation.pdf.
  3. Kennedy S, Robinson J, Hallam N. LLETZ and infertility. Br J Obstet Gynaecol 1993 Oct;100(10):965 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8217988.
  4. Hammond RH, Edmonds DK. Does treatment for cervical intraepithelial neoplasia affect fertility and pregnancy? BMJ 1990 Dec 15;301(6765):1344-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2271880.
  5. Kyrgiou M, Mitra A, Arbyn M, Stasinou SM, Martin-Hirsch P, Bennett P, et al. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis. BMJ 2014 Oct 28;349:g6192 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25352501.
  6. Jakobsson M, Gissler M, Tiitinen A, Paavonen J, Tapper AM. Treatment for cervical intraepithelial neoplasia and subsequent IVF deliveries. Hum Reprod 2008 Oct;23(10):2252-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18635529.
  7. Albrechtsen S, Rasmussen S, Thoresen S, Irgens LM, Iversen OE. Pregnancy outcome in women before and after cervical conisation: population based cohort study. BMJ 2008 Sep 18;337:a1343 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18801869.
  8. Manley KM, Draycott T. Uncertainty remains about early pregnancy outcomes after treatment for cervical intraepithelial neoplasia. Evid Based Med 2015 Apr;20(2):72 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25666018.
  9. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006 Feb 11;367(9509):489-98 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16473126.
  10. Arbyn M, Kyrgiou M, Simoens C, Raifu AO, Koliopoulos G, Martin-Hirsch P, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ 2008 Sep 18;337:a1284 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18801868.
  11. Bruinsma FJ, Quinn MA. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. BJOG 2011 Aug;118(9):1031-41 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21449928.
  12. Ortoft G, Henriksen T, Hansen E, Petersen L. After conisation of the cervix, the perinatal mortality as a result of preterm delivery increases in subsequent pregnancy. BJOG 2010 Feb;117(3):258-67 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19943823.
  13. Castanon A, Brocklehurst P, Evans H, Peebles D, Singh N, Walker P, et al. Risk of preterm birth after treatment for cervical intraepithelial neoplasia among women attending colposcopy in England: retrospective-prospective cohort study. BMJ 2012 Aug 16;345:e5174 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22899563.
  14. Shanbhag S, Clark H, Timmaraju V, Bhattacharya S, Cruickshank M. Pregnancy outcome after treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2009 Oct;114(4):727-35 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19888028.
  15. Castañon A, Landy R, Brocklehurst P, Evans H, Peebles D, Singh N, et al. Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment? BJOG 2015 Aug;122(9):1191-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25854594.
  16. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008 Jan 5;371(9606):75-84 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18177778.
  17. Sadler L, Saftlas A, Wang W, Exeter M, Whittaker J, McCowan L. Treatment for cervical intraepithelial neoplasia and risk of preterm delivery. JAMA 2004 May 5;291(17):2100-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15126438.
  18. Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, et al. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol 2012 Jan;13(1):78-88 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22177579.
  19. Canfell K, Castle P, Caruana M, Gebski V, Darlington-Brown J, Heley S, Brotherton J, Gertig D, Saville M. Protocol for Compass: a randomised controlled trial of primary HPV vs. cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women in Australia. Victorian Cytology Service Inc and The University of Sydney 2014.
  20. Medical Services Advisory Committee. Final decision analytic protocol to guide the assessment of the National Cervical Screening Program renewal. September 2012. Application 1276. Canberra: MSAC; 2014 Available from: http://www.msac.gov.au/internet/msac/publishing.nsf/Content/1276-public.

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