Role of HPV testing in the NHS Cervical Screening Programme

Abstract

www.tugsh.com Trends in Urology Gynaecology & Sexual Health September/October 2007 In the UK, cervical squamous cell carcinoma is the 11th highest cause of cancer-related mortality, with 1123 deaths attributable to the disease in 2002.1 Persistent cervical infections with human papillomaviruses (HPV) cause virtually all cervical carcinoma,2 with subtypes 16, 18, 31 and 33 being particularly high risk. Two HPV vaccines, Gardasil (a quadrivalent vaccine against types 6, 11, 16 and 18) and Cervarix (a bivalent vaccine against types 16 and 18), have been reviewed by the Joint Committee on Vaccination and Immunisation (JCVI). The recommendation of HPV vaccination for all girls aged between 12 and 13 years has recently made news headlines, with reports that the government has accepted this proposal in principle, but needs to decide whether it is financially viable. At present, only the quadrivalent vaccine is licensed in the UK. The JCVI favours the use of the most cost-effective vaccine against all endpoints, including genital warts, but feels that further analysis on the benefit of warts prevention is needed before an informed decision about the choice of vaccine can be made. The vaccines protect against strains accounting for 70 per cent of cervical cancer;3 although vaccination will not replace the screening programme, this will require review once vaccinated cohorts pass into the screening process in 10–15 years. Cervical screening aims to reduce the incidence of malignant squamous cell carcinoma of the cervix by detecting and treating the precursor lesion, cervical intraepithelial neoplasia (CIN). Screening was introduced in England in 1964 and since 1988 has been offered, by the NHS Cervical Screening Programme (NHSCSP), to all women aged 25–64, every three to five years.1,4 The programme screens almost 4 million women in England annually, and it is estimated that early detection and treatment prevents 75 per cent of cases of cervical cancer.4 The cost of cervical screening and subsequent treatment of cervical abnormalities is approximately £157 million per year in England. At present, most cervical screening is conducted using the Papanicolaou (Pap) smear test, in which cells scraped from the transformation zone (junction of endoand ectocervix) are examined cytologically for dyskaryosis. It is recognised that this method is not consistently accurate; a systematic review in 2000 found that sensitivity and specificity ranged from 30 to 87 per cent and 86 to 100 per cent, respectively.5 In the UK NHSCSP, depending on the persistence and degree of severity of dyskaryosis, colposcopy is performed to provide a histological diagnosis of CIN. Liquid-based cytology (LBC) is a new method of sampling and preparing cervical cells, in which a specimen brushed from the transformation zone is transferred into a vial of preservative fluid. This is then treated and spun to allow deposition of the cell suspension onto a slide for cytological examination. Using this technology, the incidence of inadequate smears should fall, thereby reducing women's anxiety and alleviating pressure on the workforce. The government has invested £7.2 million on the implementation of LBC and aims to utilise it throughout the UK by 2008.4 Residual material from LBC samples may also be used for molecular detection of HPV.6 There are drawbacks associated with both Pap screening and LBC, as they are relatively labour intensive and prone to subjective variability in interpretation. The discovery of high-risk HPV as a cause of virtually all cervical carcinoma has prompted international interest in the use of HPV DNA testing in cervical cancer screening programmes. HPV testing uses molecular methods to detect high-risk HPV types in cervical specimens by either a signal-amplified nucleic acid assay or target-amplified techniques such as polymerase chain reaction. There is ongoing debate regarding the optimal use of HPV testing in cervical screening initiatives. Proposed uses include: • primary screening for high-grade CIN, either alone7–9 or in combination with cytological testing;10,11 • as a triage for women with cytological findings of atypical squamous cells of unknown significance; • for surveillance of women treated for high-grade lesions.