The challenge of cervical screening: to find and treat high‐grade cervical intraepithelial neoplasia at risk of progression in women of childbearing age

In this issue of Cytopathology we publish an extensively referenced review article by Austin and Zhao describing types of cervical cancer that may not be prevented by screening. The authors describe four such types, frequently seen in medicolegal practice, which they categorize collectively as Type 2 cancers: (i) rapidly progressive carcinomas, (ii) carcinomas arising in younger women (in their 20s and 30s), (iii) carcinomas with glandular differentiation and, perhaps more surprisingly, (iv) carcinomas arising in older (postmenopausal) women. Individually these types of carcinoma are rare, but they have become relatively more frequent as regular screening has prevented the majority of cervical cancers in the populations at risk. Also in this issue of Cytopathology, Castanon et al. publish the results of a multicentre cervical cancer audit, with cytology and histology slide review, in the National Health Service Cervical Screening Programme (NHSCSP) and Repše-Fokter et al. report a similar audit of a relatively new but demonstrably successfully organized screening programme in Slovenia. How should the inevitability of false-negative tests be reconciled with public and professional expectations of cancer prevention, while simultaneously avoiding unnecessary investigation and the treatment of young women of childbearing age? False negatives may occur at any stage of the screening process from collecting the sample to colposcopy, and in any type of test. Slides look different in retrospect when the outcome of cancer is known – as recognized by the authors of both cancer audits. Even biopsies may look different in retrospect. Castanon et al. found that of biopsies reported before the eventual diagnosis of cancer as negative, cervical glandular intraepithelial neoplasia (CGIN) or cervical intraepithelial neoplasia (CIN) grade 3, 1%, 15% and 12% respectively were upgraded to cancer on review. In the same audit, 23% of cytology slides reported as negative during the 10 years before diagnosis of cancer were upgraded to high-grade dyskaryosis as were more than half of those originally reported as low grade. Repše-Fokter et al. upgraded 17 out of 33 smears that had been reported as negative, low grade or inadequate within the previous screening round in 42% of all women with cancer. It can be difficult to explain to noncytologists that small, scarce, pale dyskaryotic cells may occasionally be missed and that a single cytology sample may not be representative of an abnormality. Such cases are quite likely to result in litigation because, according to Austin and Zhao, they are disproportionately seen in interval cancers in previously screened women. Cancer audits by their nature review screening histories and slides in women who subsequently develop cancer but Farnsworth, discussing quality control of a highly successful screening programme in Australia, reminds us that women with high-grade CIN have often had previous negative tests. Of women with high-grade lesions on histology, 22% had negative cytology and 13% had negative human papillomavirus (HPV) tests within the previous 30 months. A previous negative test does not negate the value of detecting high-grade CIN on a subsequent test. In well-screened populations, increasing percentages of cancers are in previously screened women, screen-detected and in younger age groups. Incidence of invasive cervical cancer in England has been highest in women aged 30–34 since 2004, but is also increasing in those aged 25–29 and 35–39: by 2009 45% of all cervical cancers were in women in their 20s and 30s (calculated from Office for National Statistics registrations). As Marshall and Zhao point out, cancers in younger women can be difficult to prevent. In an audit carried out at Guy s & St Thomas , two-thirds of women aged 20–34 with cancer had been screened during the previous 5 years, and twothirds in that age group had screen-detected 1A or 1B1 cancers (83.3% of women aged 20–29). RepšeFokter et al. observed that cancers in previously screened women were often diagnosed at an early stage after recent high-grade cytological abnormalities. Just like high-grade CIN, early cancers may not be found on the first test; but that does not negate the clinical value of detecting them on a subsequent test. Aggressive cancers without extensive CIN3 and adenocarcinomas may explain some genuine false negatives that remain negative on review. False negatives as a consequence of abnormalities missed on cytology are an important focus for quality control