2 Clinical need and practice
2.1 The Dynamic Spectral Imaging System (DYSIS) colposcope with DYSISmap and the ZedScan I adjunctive colposcopy technologies are intended to be used with colposcopy to help identify cervical intraepithelial neoplasia (CIN) during a colposcopy examination. CIN is a term used to describe precancerous changes in cells in the surface layer of the cervix (the cervical epithelium). Most changes arise in the transformation zone, where the endocervical canal (the internal canal of the cervix) meets the external part of the cervix. This is the area examined during standard colposcopy, and from where a sample is taken for cervical screening. Less often, abnormalities occur on the inside of the cervical canal instead of the surface. These changes are known as cervical glandular intraepithelial neoplasia.
2.2 Standard colposcopy is subjective and can be associated with both inter- and intra-observer variability, particularly with lower-grade abnormalities. It is usually done using a binocular colposcope, unless the clinic has a DYSIS colposcope that incorporates a digital (video) colposcope. The adjunctive colposcopy technologies aim to evaluate cellular changes objectively, using optical or electrical impedance spectroscopy to assess the characteristics of cervical cells.
2.3 The results provided by the technologies can help a colposcopist to decide whether further treatment or biopsies are needed, by guiding them to areas that are most likely to be abnormal. If the results do not suggest any areas of abnormality, and standard colposcopy is normal, the colposcopist can be more confident that high-grade disease is unlikely to be present. It is claimed that using the devices may result in more accurate detection of cervical abnormalities and identification of the correct sites for biopsy.
2.4 The purpose of this assessment is to evaluate the clinical and cost effectiveness of the DYSIS colposcope with DYSISmap and the ZedScan I. It is a full update of NICE's diagnostics guidance on the DYSIS colposcope with DYSISmap and the Niris Imaging System, which was published in 2012. NICE's original guidance concluded that DYSIS was a clinically and cost-effective option compared with standard colposcopy. Since the guidance was published there have been changes to the care pathway (see sections 2.9 and 2.10) and changes to the CE-marked products. Also, the Niris Imaging System is no longer available.
2.5 Cervical cancer is one of the less common cancers in the UK, largely because of the NHS cervical screening programme (NHSCSP). In 2013 there were 3,200 cases of cervical cancer in the UK (Cancer Research UK), which accounted for less than 1% of all new cases of cancer. In 2014 there were 890 deaths from cervical cancer in the UK (Cancer Research UK). The main cause of cervical cancer is persistent infection with high-risk genotypes of human papilloma virus (HPV; hereafter referred to as high-risk HPV), which causes changes in the cervical cells that can progress to cervical cancer if not treated.
2.6 CIN is classified based on the depth of abnormal cells in the surface layer of the cervix seen on a diagnostic or excisional (treatment) biopsy:
CIN 1: one third of the thickness of the surface layer is affected
CIN 2: two thirds of the thickness of the surface layer is affected
CIN 3: the full thickness of the surface layer is affected.
Grades 2 and 3, often referred to as high-grade, are usually treated to prevent possible progression to cervical cancer. But expert advice suggests that CIN 2 may be managed more conservatively in people who have smaller lesions and who have not completed their family.
2.7 Precancerous changes to cells in the cervix are detected by cervical screening. People are invited, through the NHSCSP, to have cervical screening every 3 years for those aged 25 to 49 and every 5 years for those aged 50 to 64. It involves taking a sample of cells from the cervix, usually the transformation zone (see section 2.1), using a specially designed brush. The cells are preserved using liquid-based cytology kits and are sent to a cytology laboratory where they are examined under a microscope.
2.8 The criteria for reporting cervical cytology and the management protocols for results are outlined in the NHSCSP's achievable standards, benchmarks for reporting, and criteria for evaluating cervical cytopathology (commonly known as ABC3; 2013). Samples are graded depending on the degree of abnormality, known as dyskaryosis (changes to the nucleus of a cell), seen under the microscope. Finding dyskaryotic cells suggests the presence of CIN.
2.9 The current management protocols for cervical cytology are described in the third edition of the NHSCSP's colposcopy and programme management guidelines (2016). Currently, people with samples that show high-grade dyskaryosis or worse are referred for colposcopy. If low-grade dyskaryosis is seen, the residual cells collected during the cervical screen are used for high-risk HPV testing to determine whether a colposcopy referral is needed. This is part of the management protocol referred to as HPV triage. The HPV test helps to identify people who are at the greatest risk of having abnormalities that may need further investigation and treatment. If low-grade dyskaryosis is seen but HPV is not detected, the risk of having underlying abnormalities is low and the cellular changes are likely to resolve without further investigation or treatment.
2.10 In July 2016, the Department of Health announced its decision to begin HPV primary screening through the NHSCSP. In HPV primary screening, the sample is tested for high-risk HPV first. If the results are positive, a cytology test is routinely done on the residual sample. People with either low- or high-grade abnormalities are referred for colposcopy. Those whose cytology results are negative are asked to come back in 12 months. HPV primary screening has now been adopted as the standard of care in several sites in England where it was piloted. Full roll out of this pathway is expected by 2019.
2.11 Treatment for CIN aims to remove the cells either by excision or ablation. Treatment for cervical glandular intraepithelial neoplasia often needs deeper excisions than for CIN.
2.12 The management protocols for colposcopy services in England are described in the NHSCSP's colposcopy and programme management guidelines (2016). Of the 188,179 people referred for colposcopy in England between 2015 and 2016, 61% had a treatment or procedure at their first appointment. The most common procedure was diagnostic biopsy (47%), followed by an excision (12%). The most common excision was a large-loop excision of the transformation zone (LLETZ; NHS Digital 2016).
2.13 Management is guided by a colposcopist's opinion of the extent of any abnormalities seen during colposcopy. If an abnormality is found, the colposcopist may take a diagnostic biopsy (punch biopsy). Or they may opt to treat an abnormality during the first clinic appointment ('see and treat') by excising the area of abnormal cells if they believe that high-grade changes are present. The NHSCSP's colposcopy and programme management guidelines (2016) recommend that treatment should not be offered at a person's first visit to a colposcopy clinic after referral for borderline or low-grade dyskaryosis. Ablative treatments should only be done after a diagnostic punch biopsy has been taken and the results have been checked.
2.14 Biopsies are examined by a histopathologist and the results are used to help the colposcopist decide whether treatment is needed. Typically, areas of CIN 2 or worse (known as CIN 2+) would need treatment. This can be done either by excising the area of abnormal cells or by destroying them in situ (ablation). During excision, cells are usually removed using a thin electrically-heated looped wire in the LLETZ procedure. The excised tissue is sent to histopathology to confirm the extent of the abnormality and to guide further management. LLETZ is usually done in the colposcopy clinic using local anaesthetic.
2.15 Unlike excisional treatment, cells removed by ablative treatment cannot be examined by a histopathologist because they are destroyed in situ. Ablative treatments include laser ablation, cryocautery and cold coagulation.
2.16 If cervical cancer is identified, depending on the stage, conservative treatment could be offered. Treatment options for cervical cancer include cone biopsy for very early stage disease, trachelectomy, hysterectomy, radiotherapy and chemotherapy. The treatment and management of cervical cancer is described in more detail in the NICE interactive flowchart on cervical cancer and in the SIGN guideline on the management of cervical cancer.