Recommendations on screening for cervical cancer

Three recent publications have challenged parts of the new Canadian Task Force on Preventive Health Care (CTFPHC) guideline on Cervical Screening(1): the commentary by Dollin(2), the joint statement by the Society of Obstetricians and Gynaecologists, the Society of Gynaecological Oncologists, and the Society of Canadian Colposcopists(3), and the present letter by Drs. Murphy and Elit(4). These writers agree with the CTFPHC's recommendations for screening women from 30 to 70, then raise three main issues: age of commencement, whether to vary initiation according to women's individual preferences and risk assessment, and use of HPV testing.

Some of the comments have misquoted the CTFPHC, and we wish to clarify misunderstandings about the strength of the evidence, what evidence was used and why we did not recommend HPV screening, and the focus of the CTFPHC on women's needs rather than policy convenience.

Strength of evidence.
Murphy and Elit, and the three societies asserted that the evidence is weak for women between 20 and 29, and therefore the recommendations about raising the age of starting screening should be ignored and left at 21. They are wrong. Box 2(1) clearly describes moderate strength evidence for women aged 20 to 24, and 25 to 29. The recommendations are weak, because of the balance between small possible benefits and the definite harms. Therefore, women and their doctors need to discuss the recommendation and its implications to support women in deciding what starting age is appropriate.

The CTFPHC found strong evidence against pap testing women younger than 20, and strong evidence for screening in women older than 30, so that somewhere between these two ages the balance of potential benefits and likely harms changes to favour screening. When 10% of women under the age of 30 are given abnormal test results, and a large proportion then undergoes colposcopy and treatment, the harms are substantial by comparison with uncertain and very small numbers of potential cancer averted before the age of 30. Table 1 shows how small are the potential reductions in mortality: of the order of 1 per million per year for 20 to 24, and 1 per 100,000 per year for 25-29. For incidence, 1.4/100,000 for 20-24 yrs, and 3/100,000 respectively. Both the CTFPHC and the CCO review assessed three case-control studies that showed low effectiveness of screening for young women (particularly those under 25). Screening at this age appears to have little effect in reducing cancer in the succeeding five years. Thus, the potential for preventing cancer through initiation of screening at 21, and consequent treatment of precursors, as recommended by the joint societies statement(3), is uncertain and at best minimal. Even following the new guidelines for management of screen-detected abnormalities(5) will still entail substantial follow-up and some procedures on young women.

The harms of screening are not well measured: they include labelling, recovery from biopsy, the possibility of cervical incompetence and early pregnancy loss or premature delivery. Healthcare data in Canada is not routinely analysed in sufficient detail to measure how the balance changes by single years of age. However, based on the data that we have, while harms reduce with age, the incidence of disease rises steadily through this decade(6,7), and therefore the potential benefit may do so too.

The evidence used.
Dollin[2] and the joint societies' statement[3] asserted incorrectly that we based our findings solely on the outcome of mortality. To the contrary: the CTFPHC also considered the incidence of invasive cancer in each age group as a key determinant of whether to recommend screening.

Murphy and Elit(4)strongly support primary HPV screening to increase the efficacy of screening, and Dollin commends this approach.(Murphy is the lead author of Cancer Care Ontario's (CCO) cervical screening guidelines(8,9) which recommend HPV as primary screening test for women 30 and over, while Dollin and Elit were members of the advisory committee). It is disturbing that the CCO decision on HPV screening was based not on the results of trials but on the anticipated results from those trials ([6] p9 Table 2). The CTFPHC requires actual results be available before formulating its guidance.

Murphy and Elit (4) and the joint statement(3) assert that the CTFPHC should have examined evidence about precursor lesions (CIN 2 & 3) and their reduction by HPV testing and treatment. These lesions are indeed precursors, but what proportion regress and what proportion actually progress to cancer, and how much time is required for progression to occur? The evidence is limited, but it appears only a small fraction of precursors progress to cancer. The CCO review quotes several sources that concur (6)(evidentiary base page 3). Experience with many different diseases shows that relying on such surrogate endpoints often leads to false conclusions(10). Therefore the CTFPHC recommendations are conservative, do not rely on surrogate outcomes, and have reserved judgment on the benefits of HPV technology until better evidence is available.

Focus on women's needs.
Murphy and Elit(4) declare that it is more important for an organised screening program to start uniformly at age 21 than for women to make choices. "While initiation of screening based on individual preference and/or risk assessment... is neither reliable, practical nor necessary as a routine." The CTFPHC emphasises the uncertainty of the evidence, and therefore of the decision on starting to screen. The implication of the weak recommendation is to assist practitioners to discuss this uncertainty with women, who can then make decisions based on their own values and beliefs. In the current era of patient empowerment, at least their recommendations should encourage, and provide the numerical information that will enable such discussion - yet the published summaries and recommendation statements from CCO or the societies do not provide such important context. Screening programs can then focus on monitoring and increasing uptake for women over age 30, for whom recommendations are strong, because benefit is clear. We appreciate the work of the provincial screening programs and believe Drs. Murphy and Elit do them a disservice by suggesting that they cannot convey the potential risks and benefits of screening

Regardless of what we do for women below age 30, the majority of advanced cervical cancer occurs among older women who have not been tested at all, so reaching out to such underscreened women is the most important factor in reducing this disease, more than changing the test. In addition, though regular pap tests reduce incidence by over 80%, some cancers develop even among screened women, so they should still seek care for these symptoms and doctors should still investigate them.

We note that in 1991, the same group of three societies spoke out against the recommendation to reduce screening intervals to three years(11), despite the clear evidence for that change. Continuing annual screening means Canadian women have had three times more tests than they needed, and thereby were exposed to extra false positives and interventions. Once again, by refusing to accept the evidence that a later start to screening is appropriate, they persist with the North American program of overscreening. The CTFPHC understands that for many members of these societies, the new guidelines may be troublesome, since they would change long-established patterns of practice. Such change should not be made without good evidence, but change is necessary when the evidence warrants it. More credence must be given to the substantial evidence from European countries that demonstrates the lack of harms from a later start age(12).

In conclusion, we stand by the recommendations of the CTFPHC: to start pap testing in the mid twenties, after discussion with the woman involved. The CTFPHC awaits the conclusion of HPV testing trials with interest, but is unwilling to accept outcomes based only on surrogates. Instead, we wish to know whether these approaches reduce incidence and mortality from cancer. We urge provincial guideline groups and individual doctors to focus on communicating risk information to women who can then make personal choices: this includes those women who are currently having regular tests and those who are not. To assist in this process, we have produced education tools, which are available on the CTFPHC website[13].

References.

1. Canadian Task Force on Preventive Health Care. Recommendations on screening for cervical cancer. CMAJ 2013. DOI:10.1503/cmaj.121505
2. Dollin J. Commentary: Preventing cervical cancer: beyond following guidelines. CMAJ 2013. DOI;10.1503/caj.121781
3. Society of Obstetricians and Gynaecologists of Canada, Society of Gynecological Oncology of Canada, Society of Canadian Colposcopists. Position statement: recommendations on screening for cervical cancer. 20 Feb 2013.
4. Murphy J, Elit L. Cervical screening guidelines - discordance discussed. CMAJ e-letter 22 Mach 2013
5. Bentley J and the Executve Council of the Canadian Society of Colposcopists. Colposcopic Management of Abnormal Cervical Cytology and Histology. J Obstet Gynaecol Can 2012;34(12):1188-1202
6. Dickinson JA, Stankiewicz A, Popadiuk C, Pogany L, Onysko J, Miller AB. Reduced cervical cancer incidence and mortality in Canada: national data from 1932 to 2006. BMC Public Health 2012;12:992
   
7. Popadiuk C, Stankiewicz A, Dickinson J, Pogany L, Miller AB, Onysko J.Invasive cervical cancer incidence and mortality among Canadian women aged 15 to 29 and the impact of screening. J Obstet Gynaecol Can. 2012 Dec;34(12):1167-76.
8. Murphy J, Kennedy ER, Dunn S, McLachlin M, Fung MFK, Gzik D, Shier M, Paszat L. Cervical Screeening: a guideline for clinical practice in Ontario. J Obstet Gynecol Can. 2012;34(5):453-58.
9. Murphy J, Kennedy ER, Dunn S, McLachlin M, Fung MFK, Gzik D, Shier M, Paszat L Cervical Screening Evidence-based series 15-9. Cancer Care Ontario. http://www.cancercare.on.ca/toolbox/qualityguidelines/clin-program/screening-ebs/
   Accessed April 11 2013
10. Yudkin J, Lipska K, Montori V The idolatry of the surrogate.
    BMJ 2011;343:d7995 doi: 10.1136/bmj.d7995 (Published 28 December 2011)
11. Stuart GC, O'Connell G, Ferenczy A. Screening for cancer of the cervix. CMAJ 1991 145:1195b-1195
    
12. Sasieni P, Castanon A, Cuzick J The impact of cervical screening on young women: a critical review of the literature 2002-2009. NHSCCSP Doc no 31. Feb 2010.
    http://www.cancerscreening.nhs.uk/cervical/publications/nhscsp31.pdf
    Accessed April 12 2013-04-12
    
13. CTFPHC website: http://canadiantaskforce.ca/resources/

TABLE. Changes in incidence and mortality of cervical cancer in Canada [6]

n/a not available, since national incidence data not collected
* Data suppressed, since numbers less than 5.
+ Not calculated since cell sizes too small to produce meaningful result.
++ change between 1952-6 to 2002-6, then 1972-6 to 2002-6

Conflict of Interest:

None declared