Cervical cancer screening

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The UK screening programme aims to reduce cervical cancer by regular cervical smears or other methods of cytopathology. The screening programme aims to prevent cancer by detecting cytological nuclear abnormalities (dyskaryosis) that are surrogate markers for a spectrum of pre-malignant lesions categorised as grades of cervical intraepithelial neoplasia. The screening programme is mainly aimed at detecting the more common squamous abnormalities, but glandular abnormalities may also be detected.

In the UK, cytological abnormalities are graded mild, moderate or severe. This generally, but not absolutely, correlates with CIN 1, 2 and 3 respectively (mild = ~40% CIN2/3; moderate = 74-77% CIN2/3; severe = 80-90% CIN2/3). In the US and many other countries outside the UK, cytology is graded using the Bethesda system.

The current system depends on the Papanicolaou test ('Pap' test). These were traditionally known as Pap or cervical smears as cervical scrapings were smeared onto slides. Strictly speaking, they are no longer smears any cervical scrapings are now processed using liquid-based cytology. However, for convenience, the term smear remains in frequent use.

Screening using the Papanicolaou test has been very successful in countries with a well-organised system and wide coverage of the population. Confidence in the UK system has been knocked by several failures of quality control, but a surge in uptake of screening occurred in 2009 following the death of the UK media figure, Jade Goody, from advanced cervical cancer. Ironically, being under 25, she would not have been eligible for screening.

Increasing evidence suggests that HPV DNA screening may detect risk of cervical cancer better than conventional pap smear.[1][2][3][4][5] From April 2012, the UK screening programme will also perform HPV testing on cervical samples and HPV status will be incorporated into the management algorithm.

Contents

Evidence

The evidence supporting a screening programme is drawn from reduction in cervical cancer in countries that adopted screening. Four of five Nordic countries adopted screening programmes to some extent, while Norway did not. The fall in mortality due to cervical cancer was the greatest in the countries with the widest screening population and the least in Norway.[6] Similar benefits followed the introduction of the UK programme in 1988.[7][8][9]

What is less easy to quantify is the morbidity associated with cervical loop excisions for lesions that may not have progressed.

Conversely, before the success of cervical cytology was compelling, Herbert Green, a New Zealand obstetrician and gynaecologist was an early dissenter and opponent to cervical screening. He challenged the notion that invasive cervical cancer developed from carcinoma-in-situ (CIS) and did not subscribe to localised treatment of these lesions. In what was later dubbed an "unfortunate experiment", he followed a cohort of women with CIS, but who were not treated for this.[10] Subsequent follow-up of this cohort showed that CIN3 significantly increased the risk of subsequent invasive cancer.[11][12] For further information on the history of cervical cancer screening in New Zealand, see the Cartwright Report[13] and further articles in the New Zealand Medical Journal.[14][15]

Eligibility

Women ≥25 to 65 in England and Wales and ≥20 in Scotland. The screening intervals were changed in 2003 to every 3 years from 25-49, increasing to every 5 years from 50 to 65. This was not universally felt to be a good thing.[16] Women above the age of 65 with 3 consecutive normal smears are not routinely followed up.

Different rules apply to women with previous abnormal smears and/or histologically confirmed abnormalities (see below). Women who have had hysterectomies may still have a cervical vault that can be sampled.

Evidence seems to favour starting screening at age 25 rather than age 20.[17] The rationale behind this is that HPV infections in younger women can cause cytological atypia that is difficult to distinguish from genuine pre-cancerous dyskaryosis. In younger women, the natural history of these cytological changes is spontaneous resolution when the body clears the HPV infection. As initial and possibly transient HPV infection is common in this age group, detection of such cytological atypia risks in over-detection and unnecessary colposcopic interventions such as loop biopsy with attendant morbidity for lesions that would have otherwise resolved spontaneously. To give an idea of the numbers involved, the NHS cervical screening document 20 states that in 2002-03, there were 26 cases of cervical cancer in England and Wales in the age range 20-24. Routine smears in this age group would have resulted in 55000 borderline or worse smear results.[18]

Smear Results

Smear results in the UK fall into a fixed number of categories each assigned a number. The categories are mostly self-explanatory with the exception of the 'borderline' category. This encompasses a number of appearences that are not felt sufficiently serious to be labelled as definitely abnormal.

The apparently jumbled numbering is due to order in which new categories added to the system:

1 = inadequate specimen
2 = negative
8 = borderline changes
3 = mild dyskaryosis
7 = moderate dyskaryosis
4 = severe dyskaryosis
5 = severe dyskaryosis/?invasive carcinoma
6 = ?glandular neoplasia

Management of Abnormal Smears

Detailed management of how each category of result is dealt in detail by the programme guidance.[18]

Inadequate 
Repeat smear. Referral to colposcopy after 3 consecutive 'inadequates'.
Negative 
Routine recall
Borderline nuclear changes 
Referral to colposcopy if 3 squamous borderlines, but refer on first glandular (endocervical) borderline change
Mild dyskaryosis 
Guidelines suggest referral for colposcopy on first 'mild', but repeating the smear is acceptable too.
Moderate dyskaryosis 
Referral to colposcopy
Severe dyskaryosis 
Referral to colposcopy
Severe dyskaryosis/?invasive carcinoma 
Urgent referral to colposcopy (within 2 weeks)
?Glandular neoplasia 
Urgent referral to colposcopy (within 2 weeks)

References

  1. Mayrand MH, Duarte-Franco E, Coutlée F, Rodrigues I, Walter SD, Ratnam S, Franco EL. Randomized controlled trial of human papillomavirus testing versus Pap cytology in the primary screening for cervical cancer precursors: design, methods and preliminary accrual results of the Canadian cervical cancer screening trial (CCCaST). International journal of cancer. Journal international du cancer. 2006 Aug 1; 119(3):615-23.(Link to article – subscription may be required.)
  2. Mayrand MH, Duarte-Franco E, Rodrigues I, Walter SD, Hanley J, Ferenczy A, Ratnam S, Coutlée F, Franco EL. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. The New England journal of medicine. 2007 Oct 18; 357(16):1579-88.(Link to article – subscription may be required.)
  3. Bulkmans N, Berkhof J, Rozendaal L, van Kemenade F, Boeke A, Bulk S, Voorhorst F, Verheijen R, van Groningen K, Boon M, Ruitinga W, van Ballegooijen M, Snijders P, Meijer C. 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. 2007 Oct 3.(Epub ahead of print) (Link to article – subscription may be required.)
  4. Ronco G, Segnan N. HPV testing for primary cervical cancer screening. . 2007 Oct 3.(Epub ahead of print) (Link to article – subscription may be required.)
  5. Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Palma PD, Del Mistro A, Ghiringhello B, Girlando S, Gillio-Tos A, De Marco L, Naldoni C, Pierotti P, Rizzolo R, Schincaglia P, Zorzi M, Zappa M, Segnan N, Cuzick J. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. The lancet oncology. 2010 Jan 18.(Epub ahead of print) (Link to article – subscription may be required.)
  6. Lăără E, Day NE, Hakama M. Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. Lancet. 1987 May 30; 1(8544):1247-9.
  7. Sasieni P, Cuzick J, Farmery E. Accelerated decline in cervical cancer mortality in England and Wales. Lancet. 1995 Dec 9; 346(8989):1566-7.
  8. Quinn M, Babb P, Jones J, Allen E. Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics. BMJ (Clinical research ed.). 1999 Apr 3; 318(7188):904-8.
  9. Peto J, Gilham C, Fletcher O, Matthews FE. The cervical cancer epidemic that screening has prevented in the UK. Lancet. 2004 Jul 17-23; 364(9430):249-56.(Link to article – subscription may be required.)
  10. Green GH. The significance of cervical carcinoma in situ. American journal of obstetrics and gynecology. 1966 Apr 1; 94(7):1009-22.
  11. McIndoe WA, McLean MR, Jones RW, Mullins PR. The invasive potential of carcinoma in situ of the cervix. Obstetrics and gynecology. 1984 Oct; 64(4):451-8.
  12. McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, Skegg DC. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. The lancet oncology. 2008 May; 9(5):425-34.(Link to article – subscription may be required.)
  13. 1987 Cartwright Report
  14. Paul C. New Zealand's cervical cytology history: implications for the control of cervical cancer. The New Zealand medical journal. 2004 Nov 26; 117(1206):U1170.(Link to article – subscription may be required.)
  15. Jones R, Fitzgerald N. The development of cervical cytology and colposcopy in New Zealand: 50 years since the first cytology screening laboratory at National Women's Hospital. The New Zealand medical journal. 2004 Nov 26; 117(1206):U1179.(Link to article – subscription may be required.)
  16. Raffle AE. Cervical screening. BMJ (Clinical research ed.). 2004 May 29; 328(7451):1272-3.(Link to article – subscription may be required.)
  17. Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ (Clinical research ed.). 2009; 339:b2968.(Epub)
  18. a b Colposcopy and Programme Management - Guidelines for the NHS Cervical Screening Programme. NHSCSP Publication No 20. April 2004. (pdf version)