Cervical cancer is one of the few cancers where screening can detect precancerous cell growth. These abnormalities can be treated, preventing the development of cancer.
In Australia, the National Cervical Screening Program (NCSP) using the Pap test began in 1991. Since then, Australia’s cervical cancer incidence and death rates have halved.
Implementation of the HPV vaccination program will significantly reduce the average lifetime risk of cervical cancer. Despite the efficacy of the vaccine against the high-risk HPV types that cause most cervical cancers, cervical screening will remain critical in cervical cancer prevention. The vaccine is not effective against existing HPV infections and does not prevent all high-risk HPV types, meaning a significant proportion of cervical cancers will not be prevented.
While cervical screening remains integral to cervical cancer prevention, the NCSP will need to change as the vaccinated cohort ages to maintain its effectiveness and cost-efficiency. There is a substantial body of evidence that screening women younger than 25 years, and screening more frequently than three yearly, does not substantially reduce the incidence of invasive cervical cancer. Accumulating evidence on the value of primary HPV testing and triage by cytology or other tests will also have implications for the NCSP.
The NCSP Renewal has assessed the evidence for screening tests and pathways, the screening interval, age range and commencement for both vaccinated and non-vaccinated women, to determine a cost-effective screening pathway and program model.
The Pap test
The Pap test (named after its developer, Dr George Papanicolaou) is the most widely used cancer screening test in the world. Typically, cervical cancer takes 10 years or more to develop. The value of the Pap test is as a screening tool in a program of re-screening at regular intervals – to detect pre-cancerous abnormalities during this long pre-invasive stage – rather than a single opportunistic test. Abnormalities detected by a Pap test can be monitored, or, if required, further investigated and early treatment initiated.
Cervical screening with the Pap test began in British Columbia (Canada) in 1949. A large number of observational studies have shown reductions in cervical cancer incidence and mortality over time attributable to screening programs. In Australia, cervical cancer incidence and death rates halved between 1991, when the NCSP began, and 2002 and have remained stable since.
Incidence, after halving from 17.2 new cases per 100,000 women in 1991, has remained at around nine new cases per 100,000 women from 2002 to 2010, for women aged 20–69. The historical low of around two deaths per 100,000 women has been sustained from 2002 to 2011, for women aged 20–69. These gains can be attributed, in part, to the success of the NCSP.
The estimated average cumulative lifetime risk of cervical cancer in Australian women with the current screening program is ~0.68%. However cytological screening has not been as effective in reducing other types of cervical cancer, particularly adenocarcinomas, because of difficulties in sampling and cytological interpretation of glandular cells. A recent population-based cohort study of more than 1200 Swedish women with cervical cancer has shown that cervical screening not only reduced the risk for invasive cervical cancer but that women with screen-detected cancers had improved relative survival. Among women with symptomatic cancer, those who had been screened according to recommendations (presented within the screening interval) had better outcomes than those overdue for screening.
Potential adverse effects
No screening test is 100% accurate. Like all screening tests, the Pap test is performed on asymptomatic women. False positive results may occur. False negative results are common and vary across settings. It should be noted that accurate information on false negative rates for cytology against an independent reference standard is not available for Australia.
Even minor abnormalities can cause anxiety for some women. Women who receive false negative results may experience delays in diagnosis or treatment. False negative results may also create a false sense of security that may cause warning symptoms to be ignored.
Abnormal test results can lead to more frequent testing and invasive diagnostic procedures. Risks associated with procedures such as colposcopy and cervical biopsy include vaginal bleeding, pain, infection and failure to diagnose (due to inadequate sampling).
In addition to the inherent risks of surgical therapies, some treatments for cervical abnormalities have been associated in some studies with adverse pregnancy outcomes including preterm delivery, low birthweight although results are not consistent across all studies.
Screening age range and intervals
The current NCSP policy recommends all women who have ever been sexually active should commence having Pap tests between the ages of 18 and 20 years, or within two years after beginning sex, whichever is later.
A substantial body of evidence has found that screening in women younger than 25 years of age has little or no impact on the risk of developing invasive cancer. The International Agency for Research on Cancer (IARC) recommends regular cervical screening begin at age 25. This was reiterated in the NCSP Renewal which recommended a screening start age of 25. In the post-vaccination era it is expected that the risk of cancer in women aged 25 years and under, who were vaccinated prior to exposure to HPV, will be low enough to make screening such young women unjustifiable.
Australia’s two-yearly screening interval is conservative, with many countries recommending three years or more between tests. An Australian evaluation has supported international evidence that three yearly screening is safe and screening more frequently does not substantially reduce the number of cervical cancer cases or deaths. Similar reductions in cervical cancer incidence and mortality have been achieved in Australia, which has a two-yearly screening policy, and the UK, where the policy is predominantly three-yearly screening. IARC recommends three-yearly screening for women aged 25 to 49 and five-yearly screening for women aged 50 to 64 – a recommendation adopted by the NHS Cervical Screening Programme in the United Kingdom.
The NCSP Renewal has recommended that screening take place at an interval of five years, this is primarily due to recommendations to use HPV testing at the primary screening tool, in place of Pap tests.
Impact of HPV vaccination on screening
As successive cohorts of girls are vaccinated, and the vaccinated cohorts mature, the risk of cervical cancer will fall. Prophylactic HPV vaccination is expected to eliminate high-grade intraepithelial lesions and cancers attributable to HPV 16 and 18. Removing the most dangerous (and more cytologically-apparent) cervical abnormalities – and leaving behind the more equivocal ones – may reduce the positive predictive value of cytology. In the era of HPV vaccination, as the population prevalence of HPV 16 and 18 falls, different screening tests and technologies need to be re-evaluated.
Screening will remain necessary, even for vaccinated women. The vaccine does not cover all HPV types that can lead to cervical cancer and may not be effective in women exposed to HPV prior to vaccination. It will take many years for the impact of the vaccine – delivered to adolescent girls – to reduce the incidence of invasive cervical cancer in women in middle age and beyond. As the proportion of vaccinated women increases, screening policy and protocols, including age of commencement and screening intervals, have been reconsidered through the NCSP Renewal.
New screening technologies
In the past decade, a desire to improve the accuracy and reliability of cervical screening and an increased understanding about the role of HPV in cervical cancer has led to the development of new cervical screening technologies, outlined in this section. Appropriate consideration has recently been given to their role in the NCSP, via the NCSP Renewal
HPV DNA testing
Due to the relationship between persistent infection with high-risk types of HPV and the development of cervical cancer, testing for the presence of (high-risk) HPV DNA in cervical cell specimens has the potential to identify women at increased risk of developing cervical cancer. Women who test HPV-negative are at very low risk for CIN3 and cancer for at least five years. For women who are cytology-negative but HPV-positive, HPV 16-positive or HPV 16/18-positive results are associated with medium-term risk of CIN3 or cancer.
Research has focused on the application of HPV testing:
- in primary cervical screening;
- in triage of women with possible or low grade cervical abnormalities; and
- as a ‘test of cure’ following treatment for high grade precancer.
A large body of evidence, including data from randomised trials in developed countries, has shown HPV testing in primary screening is superior to cytology. Analysis of four European randomised controlled trials found that, compared with cytology, HPV-based screening provided 60–70% greater protection against invasive cervical cancers. HPV DNA testing in cervical screening detects high-grade lesions earlier, thus preventing more invasive cervical cancers.
The NCSP Renewal found that screening with the HPV test is projected to decrease cervical cancer incidence by 15–18% and cervical cancer mortality by 16–18% (depending on triage of HPV-positive women), compared with current practice.
HPV DNA testing has greater sensitivity, but lower specificity for high-grade abnormalities, compared with cytology, and better reproducibility. Because of its high sensitivity and objectivity, there is growing support for the use of HPV DNA testing in primary screening programs.
A clinical trial comparing Pap tests every three years with HPV testing every six years is currently running in Australia. It is the first large-scale clinical trial internationally to assess these screening tests in an HPV vaccinated population.
Screening using HPV testing has the potential to improve identification of adenocarcinoma and its precursors.
Using the HPV test as a primary screening tool allows for development of population-based screening recommendations based on individual risk assessment rather than vaccination status, which will change over time as vaccinated cohorts reach screening age. Given HPV types 16, 18 and 45 account for the greatest proportion of infections causing cervical cancer, screening tests that provide genotyping are expected to improve risk stratification of HPV-positive women in cervical screening programs.
Concerns about overdiagnosis with HPV testing have been raised because of its lower cross-sectional specificity for high-grade disease, when compared to cytology. However, this can be managed through triage of HPV-positive women with cytology or partial genotyping, so that women are managed on the basis of whether HPV types 16, 18 or 45 are present. There are also a variety of emerging technologies designed to help triage HPV-positive women to diagnostic evaluation. Overdiagnosis can be further reduced by starting screening at 25 years of age.
Recent research in other developed countries suggests primary HPV DNA testing (for high-risk types) could be cost-effective in unvaccinated women, if an appropriate triage procedure is used in HPV positive women and women are screened at an appropriate age.
HPV testing in Australia As a result of the NCSP Renewal, HPV testing from 25 years of age, at an interval of five years has been recommended as the preferred pathway for screening in Australia. See the Policy context section of this chapter for more information.
The NCSP Renewal identified options for HPV screening in Australia that were predicted to result in both cost and life years savings, compared with current practice. The greatest gains in both effectiveness and cost savings were associated with primary HPV testing, with partial genotyping for HPV 16/18, in which women with these HPV types are referred directly for diagnostic evaluation.
Currently in Australia, HPV DNA testing is also recommended for use in women following treatment of a high-grade abnormality. The test is used to determine whether the virus has been cleared and whether women can thus be discharged back to routine screening. A prior analysis by the Medical Services Advisory Committee (MSAC) on HPV triage testing for women with possible or low-grade squamous intra-epithelial lesions concluded that, compared with repeat recall cytology at one year, it was safe and effective, but not cost effective in the Australian setting at the current price of HPV testing. This option was re-evaluated in context of NCSP Renewal, however the most effective and cost-saving strategies involved using HPV as a primary screening test, not as a triage test after primary screening with cytology.
Liquid-based cytology is a technique where the cervical cells collected on the sampling instruments are suspended in liquid. At the laboratory the liquid sample is filtered to remove unnecessary material such as blood, bacteria and other matter. The cells are then deposited as a single layer onto a slide, stained and examined under a microscope.
In 2009 MSAC reviewed liquid-based cytology – both automated and with manual reading – and concluded that both were safe and at least as effective as conventional Pap smears, but "not cost effective at the price requested". The evidence suggests that there is no substantial difference between manually read liquid-based cytology and conventional cytology in sensitivity for high-grade disease. However, the MSAC reported that two medium-quality Australian studies have found image read liquid-based cytology (using the ThinPrep Imager system) identified more histologically confirmed CIN2+ lesions than conventional cytology.
Sensitivity analyses have demonstrated new technologies are more cost-effective in the context of three-yearly screening. In its assessment report the MSAC noted that as changes due to vaccination are realised "reassessment of the cost-effectiveness of these technologies … would be warranted as part of any review of screening strategies and technologies". Liquid-based cytology screening was re-evaluated in the context of the NCSP Renewal evaluation, however as noted in HPV testing in Australia the most effective and cost-effective screening strategies overall involved primary HPV testing.
Studies show self-collected cervicovaginal samples show promising performance, with sensitivity that may approach that of physician-collected samples for HPV detection, supporting the potential use of self-sampling in primary cervical cancer screening.
The NCSP Renewal evaluation found that HPV self-collection has a moderate-high sensitivity and comparably high specificity for detecting CIN2+, compared to clinic HPV testing.
Self-sampling could increase participation by women who do not participate in current screening programs. Randomised controlled trials and cohort studies in other developed countries have shown that offering self-sampling to women who did not attend regular screening increases participation significantly.
Self-sampling can supplement the organised screening program for under-screened and unscreened women. To ensure that the safety and efficacy of self-sampling, the test should only be provided in conjunction with patient counselling and clinical interpretation of results, patient follow-up and confirmatory testing for positive results when required and testing in a safe environment with infection control procedures.
- Australian Institute of Health and Welfare. Cervical screening in Australia 2011–2012. Canberra: AIHW; 2014. Report No.: Cancer series no.82. Cat. no. CAN 79. Available from: http://aihw.gov.au/publication-detail/?id=60129546865.
- International Agency for Research on Cancer. IARC handbooks of cancer prevention: volume 10 - cervix cancer screening. Lyon: IARC Press; 2005 Available from: http://www.iarc.fr/en/publications/pdfs-online/prev/handbook10/HANDBOOK10.pdf.
- Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ 2009 Jul 28;339:b2968 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19638651.
- Brotherton JM, Gertig DM. Primary prophylactic human papillomavirus vaccination programs: future perspective on global impact. Expert Rev Anti Infect Ther 2011 Aug;9(8):627-39 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21819329.
- Richart R, Lopes P. Prevention and control of cervical cancer in the new millenium, an international commitment. Conclusions: cervical cancer control, priorities and new directions. Apr 13-16; Paris. 2003: Eurogin; 2003.
- Dickinson JA. Cervical screening: time to change the policy. Med J Aust 2002 Jun 3;176(11):547-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12064988.
- Creighton P, Lew JB, Clements M, Smith M, Howard K, Dyer S, et al. Cervical cancer screening in Australia: modelled evaluation of the impact of changing the recommended interval from two to three years. BMC Public Health 2010 Nov 26;10:734 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21110881.
- Andrae B, Andersson TM, Lambert PC, Kemetli L, Silfverdal L, Strander B, et al. Screening and cervical cancer cure: population based cohort study. BMJ 2012 Mar 1;344:e900 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22381677.
- Cuzick J, Clavel C, Petry KU, Meijer CJ, Hoyer H, Ratnam S, et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 2006 Sep 1;119(5):1095-101 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16586444.
- TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) Group, Sharp L, Cotton S, Cochran C, Gray N, Little J, et al. After-effects reported by women following colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial. BJOG 2009 Oct;116(11):1506-14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19583712.
- 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16473126.
- 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18801868.
- 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22899563.
- Department of Health and Ageing. NCSP policies. [homepage on the internet] Canberra: DoHA; 2017 Nov 20 [cited 2013 Oct 10; updated 2011 May 16]. Available from: http://www.health.gov.au/internet/screening/publishing.nsf/Content/NCSP-Policies-1.
- Medical Service Advisory Committee. National Cervical Screening Program Renewal: Executive summary. Commonwealth of Australia; 2013 Nov. Report No.: MSAC application no. 1276. Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/754127911763F571CA257B8A001ADDC5/$File/WebAccessiblility_Combined_Executive_summary__Final_27Nov2013_SentToDoHA.pdf.
- Canfell K, Sitas F, Beral V. Cervical cancer in Australia and the United Kingdom: comparison of screening policy and uptake, and cancer incidence and mortality. Med J Aust 2006 Nov 6;185(9):482-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17137451.
- Schiffman M. Integration of human papillomavirus vaccination, cytology, and human papillomavirus testing. Cancer 2007 Jun 25;111(3):145-53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17487850.
- Franco EL, Mahmud SM, Tota J, Ferenczy A, Coutlée F. The expected impact of HPV vaccination on the accuracy of cervical cancer screening: the need for a paradigm change. Arch Med Res 2009 Aug;40(6):478-85 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19853188.
- Bosch FX, Castellsagué X, de Sanjosé S. HPV and cervical cancer: screening or vaccination? Br J Cancer 2008 Jan 15;98(1):15-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18182975.
- Katki HA, Kinney WK, Fetterman B, Lorey T, Poitras NE, Cheung L, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncol 2011 Jul;12(7):663-72 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21684207.
- Joint European Cohort Study, Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, et al. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ 2008 Oct 13;337:a1754 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18852164.
- Kjær SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst 2010 Oct 6;102(19):1478-88 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20841605.
- Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014 Feb 8;383(9916):524-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24192252.
- Franceschi S, Denny L, Irwin KL, Jeronimo J, Lopalco PL, Monsonego J, et al. Eurogin 2010 roadmap on cervical cancer prevention. Int J Cancer 2011 Jun 15;128(12):2765-74 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21207409.
- Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009 Apr 2;360(14):1385-94 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19339719.
- New Technologies for Cervical Cancer screening (NTCC) Working Group, Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol 2010 Mar;11(3):249-57 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20089449.
- 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22177579.
- Bulkmans NW, Berkhof J, Rozendaal L, van Kemenade FJ, Boeke AJ, Bulk S, et al. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet 2007 Nov 24;370(9601):1764-72 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17919718.
- Carozzi FM, Del Mistro A, Confortini M, Sani C, Puliti D, Trevisan R, et al. Reproducibility of HPV DNA Testing by Hybrid Capture 2 in a Screening Setting. Am J Clin Pathol 2005 Nov;124(5):716-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16203283.
- Bulk S, Bulkmans NW, Berkhof J, Rozendaal L, Boeke AJ, Verheijen RH, et al. Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high-risk HPV testing at baseline and at 6-months. Int J Cancer 2007 Jul 15;121(2):361-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17354241.
- Cuzick J, Arbyn M, Sankaranarayanan R, Tsu V, Ronco G, Mayrand MH, et al. Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 2008 Aug 19;26 Suppl 10:K29-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18847555.
- CBCSP-HPV Study Group, Chen HC, Schiffman M, Lin CY, Pan MH, You SL, et al. Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer. J Natl Cancer Inst 2011 Sep 21;103(18):1387-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21900119.
- VCS Compass. Compass. [homepage on the internet] Melbourne: VCS Compass; 2014 Jan 1 Available from: http://www.compasstrial.org.au/.
- Canfell K. Models of cervical screening in the era of human papillomavirus vaccination. Sex Health 2010 Sep;7(3):359-67 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20719228.
- Guan P, Howell-Jones R, Li N, Bruni L, de Sanjosé S, Franceschi S, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 2012 Nov 15;131(10):2349-59 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22323075.
- Department of Health and Ageing. New technologies for cervical screening. [homepage on the internet] Canberra: DoHA; 2008 May [cited 2013 Oct 8; updated 2011 May 17]. Available from: http://www.health.gov.au/internet/screening/publishing.nsf/Content/new-technology-policy.
- Medical Services Advisory Committee. Human papillomavirus triage test for women with possible or definite low-grade squamous intraepithelial lesions. Canberra: Commonwealth of Australia; 2009 Mar. Report No.: MSAC reference 39. Available from: http://www.health.gov.au/internet/msac/publishing.nsf/Content/8FD1D98FE64C8A2FCA2575AD0082FD8F/$File/39_MSAC_Assessment_Report.pdf.
- Medical Services Advisory Committee. Automation-assisted and liquid-based cytology for cervical cancer screening. Canberra: Commonwealth of Australia; 2009 Mar. Report No.: MSAC application 1122. Available from: http://www.health.gov.au/internet/msac/publishing.nsf/Content/BAE45713D7D0FDEBCA257817001CB46D/$File/1122_MSAC_Assessment_Report.pdf.
- Ronco G, Cuzick J, Pierotti P, Cariaggi MP, Dalla Palma P, Naldoni C, et al. Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial. BMJ 2007 Jul 7;335(7609):28 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17517761.
- Petignat P, Faltin DL, Bruchim I, Tramèr MR, Franco EL, Coutlée F. Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis. Gynecol Oncol 2007 May;105(2):530-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17335880.
- Szarewski A, Cadman L, Mallett S, Austin J, Londesborough P, Waller J, et al. Human papillomavirus testing by self-sampling: assessment of accuracy in an unsupervised clinical setting. J Med Screen 2007;14(1):34-42 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17362570.
- Schmeink CE, Bekkers RL, Massuger LF, Melchers WJ. The potential role of self-sampling for high-risk human papillomavirus detection in cervical cancer screening. Rev Med Virol 2011 May;21(3):139-53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21538664.
- Jones HE, Wiegerinck MA, Nieboer TE, Mol BW, Westhoff CL. Women in the Netherlands prefer self-sampling with a novel lavaging device to clinician collection of specimens for cervical cancer screening. Sex Transm Dis 2008 Nov;35(11):916-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18665020.
- Dzuba IG, Díaz EY, Allen B, Leonard YF, Lazcano Ponce EC, Shah KV, et al. The acceptability of self-collected samples for HPV testing vs. the pap test as alternatives in cervical cancer screening. J Womens Health Gend Based Med 2002 Apr;11(3):265-75 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11988136.
- Waller J, McCaffery K, Forrest S, Szarewski A, Cadman L, Austin J, et al. Acceptability of unsupervised HPV self-sampling using written instructions. J Med Screen 2006;13(4):208-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17217611.
- Bais AG, van Kemenade FJ, Berkhof J, Verheijen RH, Snijders PJ, Voorhorst F, et al. Human papillomavirus testing on self-sampled cervicovaginal brushes: an effective alternative to protect nonresponders in cervical screening programs. Int J Cancer 2007;120(7): 1505-1510. Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17205514.
- Gök M, Heideman DA, van Kemenade FJ, Berkhof J, Rozendaal L, Spruyt JW, et al. HPV testing on self collected cervicovaginal lavage specimens as screening method for women who do not attend cervical screening: cohort study. BMJ 2010 Mar 11;340:c1040 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20223872.
- Self-Sampling Study Working Group, Giorgi Rossi P, Marsili LM, Camilloni L, Iossa A, Lattanzi A, et al. The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600). Br J Cancer 2011 Jan 18;104(2):248-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21179038.
- Szarewski A, Cadman L, Mesher D, Austin J, Ashdown-Barr L, Edwards R, et al. HPV self-sampling as an alternative strategy in non-attenders for cervical screening - a randomised controlled trial. Br J Cancer 2011 Mar 15;104(6):915-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21343937.
- Virtanen A, Anttila A, Luostarinen T, Nieminen P. Self-sampling versus reminder letter: effects on cervical cancer screening attendance and coverage in Finland. Int J Cancer 2011 Jun 1;128(11):2681-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20669228.
- Wikström I, Lindell M, Sanner K, Wilander E. Self-sampling and HPV testing or ordinary Pap-smear in women not regularly attending screening: a randomised study. Br J Cancer 2011 Jul 26;105(3):337-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21730977.