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The Role of Colposcopy in Cervical Precancer CHAPTER 1 CHAPTER CHAPTER 1 CHAPTER CHAPTER 1. The role of colposcopy in cervical precancer CHAPTER 1 CHAPTER A positive diagnostic test result squamous intraepithelial lesion and where low rates of default from reveals an abnormality or disease. (HSIL) level (cervical intraepithelial follow-up exist, the threshold for Advice about management is usual- neoplasia grade 2 [CIN2] or greater). treatment may be higher, especially ly accepted willingly. When a wom- However, in many countries with in young women. The management an receives an abnormal cervical established screening programmes of screen-positive women would screening test result, the expecta- tions and fears that she carries are Fig. 1.1. Relative rates of human papillomavirus (HPV) infection, low-grade quite different. Cervical screening squamous intraepithelial lesion (LSIL), and cervical cancer (high-grade tests – whether visual inspection, squamous intraepithelial lesion [HSIL]). cervical cytology, or human papil- 0.5 million cervical cancer cases lomavirus (HPV) tests – do not give a diagnosis; rather, they modify the risk for an individual of developing 10 million HSIL cervical cancer. The progression to precancer and cancer is slow and 60 million is a very uncommon outcome for LSIL/innocent screen-positive women (Fig. 1.1). condylomata The threshold of abnormality at which the risk of cancer outweighs any disadvantage of treatment varies 300 million cases according to patient characteristics of HPV infection and local service considerations. The World Health Organization (WHO) advises treatment at the high-grade Chapter 1. The role of colposcopy in cervical precancer 1 Fig. 1.2. The ideal, dichotomous screening test. cancer. The problem of imperfect sensitivity and specificity is illustrat- ed in Fig. 1.3. Visual inspection with acetic acid (VIA) is fast becoming the de facto screening method of choice in many regions where cytology and HPV testing are out of reach. A “screen- and-treat” approach is gaining pop- ularity as an efficient method of reaching large numbers of women in difficult circumstances. However, the specificity of VIA is poor, and the difficulty of missing endocervical le- sions (whether they are squamous or glandular) is a real problem. Over- treatment of women with false-posi- be much easier if the results of whom there is a risk of precancer. tive VIA test results is perceived as screening tests were diagnostic and Because of this, cytology testing has a necessary trade-off to reduce the dichotomous. An ideal screening test to be performed relatively frequently overall incidence of cervical cancer. would provide two possible answers, (3–5-yearly). The long natural history Thus, screening tests (VIA, cy- and management advice would be of cervical cancer is forgiving of the tology, and HPV testing) are imper- simple (Fig. 1.2). relatively poor sensitivity of cytology. fect, and women with an abnormal But current screening tests for Also, cytology will sometimes primary screening test need further cervical precancer are neither com- recognize cells that are very mildly consideration before reflex referral to pletely sensitive nor absolutely spe- abnormal, or even of a “borderline” colposcopy and/or management. For cific. For example, testing for on- nature: borderline nuclear abnormal- those women in whom a suspicion cogenic (or high-risk) HPV will pick ity, and atypical squamous cells of of CIN2 has been reported, referral up almost all cervical precancerous undetermined significance (ASCUS). to colposcopy is still the appropriate lesions but will also test positive These categories of abnormality cre- advice. (When considering treat- in women who have innocent and ate headaches and frustration for ment, lesser grades of abnormality, transient high-risk HPV infection. In both clinician and patient. They in- or CIN2 with negative p16, the cost– a recent study, 73% of women with clude mostly women who are not at benefit equation is less certain.) The a positive oncogenic HPV test also a high risk of progression, as well as concept of triage is to use other tests had a negative or normal smear (Kat- a minority of women who are. Clear- for women who have an imprecise ki et al., 2011). Cytology, in contrast, ly, the ideal test – not yet available primary screening test report, so is far more specific than HPV testing – would identify only the women who that those women who have a gen- but will miss a number of women in are at a high risk of progression to uine risk of progression to cancer Fig. 1.3. (a) The ideal screening test. (b) The real screening test. a b 2 CHAPTER 1 CHAPTER may be identified and referred for Fig. 1.4. Age-standardized incidence of invasive cervical cancer and colposcopy and management. Also, coverage of screening in England, showing a decrease in incidence after just as importantly, women who are the introduction of a national call-and-recall screening programme. at a very low risk of progression may be spared the interventions of biopsy and/or treatment. Colposcopy is also important in avoiding overtreatment that may occur with “screen-and- treat” programmes where false-pos- itive rates may be very high (Basu et al., 2015). Finally, colposcopy may recognize invasive cancer not her- alded by a screening test. 1.1 Traditional screening: rationale and practice Systematic high-coverage and quali- ty-assured population screening and recognize morphological changes cancer, but rather the subsequent treatment for precursors to cervi- allows cytologists to report different management of screen-positive cal cancer are highly effective. The degrees of abnormality, classified as women. Screen-positive women conditions for an ideal screening test borderline, low-grade, or high-grade may be stratified according to risk as enunciated by Wilson and Jung- in squamous or glandular cells. and either referred to a colposcopist ner (1968) apply very precisely to High-grade smear abnormalities are or retested some time later. Classi- cervical cancer. The disease has a associated with a higher risk of cer- cally, colposcopic examination facili- long precancerous phase, effective vical cancer development over the tates the recognition and localization screening tests are available and are subsequent decade, and low-grade of genuinely high-grade abnormality easily performed, and the disease and borderline smears are associat- within the “at-risk” epithelium – i.e. is common enough to justify the ex- ed with a dramatically lower risk. the transformation zone (TZ) – and pense of population screening, even Of course, it is not the screen- facilitates either confirmatory biopsy in low- and middle-income countries ing itself that prevents cervical or excision/ablation of the TZ, or both. (LMICs) (Denny and Prendiville, 2015). Finally, there are effective and Fig. 1.5. Projected cervical cancer deaths without any screening (England low-morbidity preventive treatments and Wales). Dashed line represents cervical cancer deaths that would have of proven value for screen-positive happened after 1987 without screening. Solid line shows annual deaths women. In those countries and re- from 1953 to 2002. Arrow indicates start of national screening in 1988. gions that have implemented quali- ty-assured, high-coverage call-and- recall screening programmes for cervical precancer, large reductions have been demonstrated in the rates of both incidence of and mor- tality from cervical cancer (Figs. 1.4 and 1.5). 1.2 Management of screen-positive women In the traditional system, a cervi- cal smear test is the usual screen- ing tool (Fig. 1.6). The microscopic examination of cellular material to Chapter 1. The role of colposcopy in cervical precancer 3 Fig. 1.6. Traditional algorithm for screen-positive cases. routine office or outpatient LLETZ could be learned and performed, compared with laser treatment or cold-knife cone biopsy, meant that the threshold for treatment fell. At about the same time, reporting rates for low-grade and borderline ab- normalities varied enormously. In Ireland’s National Cancer Screen- ing Service, for example, at the beginning of its cervical screening programme all smears were sent to a laboratory in the USA. Of these specimens, 14.9% were reported as “not normal”, rates similar to those Established treatment modalities are electrosurgical excision procedure for VIA. Finally, as the very high effective. Through well-organized (LEEP) in the USA, was introduced sensitivity of oncogenic HPV testing screening programmes and the man- as a simple excisional outpatient became apparent, the test became agement of screen-positive women, treatment (Prendiville et al., 1989). used widely, either on its own or in incidence and mortality rates have This technique largely replaced la- combination with cytology. The man- been reduced significantly (Arbyn ser treatment and other destructive agement of screen-positive women et al., 2009; IARC, 2005; Miller, methods because of its simplicity, became more complex. The optimal 1993; Peto et al., 2004; Sasieni et cost–effectiveness, and facility for “next step” for most women with any al., 2003). For many years, this sys- comprehensive histological assess- “not normal” smear is no longer au- tem or model of screen, colposcope, ment of the removed TZ. In select- tomatic referral for colposcopy and and treat selected patients has been ed cases it obviated the need for a treatment. standard and highly successful. preliminary colposcopically directed But the protocol is not perfect. It biopsy. 1.3 Clinical guidelines was a practical and workable system Although it has been known for 30 years ago. For example, in the some time that low-grade abnormal- Against this background, some na- United Kingdom, women were not, ities have a low risk of progression tional societies of colposcopy and at that time, referred for colposcopic (Moscicki et al., 2010), it became cervical pathology have taken on the examination unless the cytologist clear that some cytological low- responsibility of generating clinical considered there to be a significant grade or borderline smears harbour guidelines for physicians and colpos- risk of progression to cancer – in oth- higher-grade lesions.
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