• The normal cervix and the colposcopy examination
  A. Singer (UK)
  

Colposcopy is the visual examination of the epithelial cervix using either uni or binocular vision. Specific abnormalities associated with both squamous and glandular precancer can be identified especially after the application of a 5% acetic acid solution. After this application the abnormalities become visible as a result to changes in the epithelium and blood vessels in the stroma. These changes occur within an area of the cervix called the transformation zone, an area bounded by the junction of vaginal epithelium and the glandular epithelium arising from the endocervix (canal). Within this area a change occurs in which and glandular epithelium changes to squamous by a process of transformation, called metaplasia. The upper border of this metaplastic change is called the new   squamo columnar junction. The inability to see this junction means that abnormality may exist higher up in the endo cervix.

A sample of any abnormality within the transformation zone can be taken by a simple punch biopsy. Abnormality extending into the endocervix above the new squamo columnar junction will need a limited surgical excision of the endocervix. Colposcopy is an essential part of the diagnosis and treatment of cervical precancer. It is indicated in the presence of abnormal cytology or in the finding of a positive HPV report and also when there are clinical symptoms and signs of the early invasive cancer.

• Update of pathology and cytology for colposcopists
  C. Bergeron (France)
  

As molecular evidence increased and was carefully correlated with epidemiologic studies, it is now clear that CIN 1 (e.g. mild dysplasia, usually with koilocytes) represents the histologic correlate for productive HPV infection, while CIN2 (at least for some) but definitely CIN3/CIS are identified as a morphologic indication of HPV oncogene-induced cell transformation. This understanding leads to the return of a binary risk-based managerial approach to cervical pathology: CIN1 lesions are considered low-grade squamous intraepithelial lesions (LSIL) and managed with observation, whereas CIN2/CIN3/CIS lesions are lumped together as high-grade squamous intraepithelial lesions (HSIL) and warranted resection.

This two-tiered risk schema informed the Bethesda Classification System for Cervical Cytology, first introduced in 1988 and refined 3 times, most recently in 2014.  In 2012, the Lower Anogenital Squamous Terminology (LAST) project further advocated for the use of LSIL/HSIL terminology not only in the uterine cervix, but also elsewhere in the male and female genital tracts, as did the 4th edition of the World Health Organization’s text on gynaecologic neoplasia. Thus today, we have a unified, biologically based terminology for both cytology and histology that extends to the whole spectrum of cervical neoplasia and helps to guide management.

• Colposcopy of “abnormal” cervix
  A. Singer (UK)
  

The epithelium containing  squamous precancer within the transformation zone has certain characteristics. These reside within the epithelium or in the presence of blood vessels penetrating the epithelium and existing in the underlying stroma. The epithelium when painted with a solution of 5% acetic acid takes on a white appearance due to the obstruction of reflected light from the underlying stroma due to the cellularity of the epithelium.This epithelium is now called aceto-white epithelium and has all degrees of whiteness from a partially translucent appearance to one  with extreme white denseness. The blood vessels can appear as red spots on the white epithelial background and this change is called punctuation. Likewise a mosaic appearance in the epithelium is also associated with abnormality and is called mosaic change. Both changes are as a result of increasing epithelial vascularity. An extreme form of this vascularity is called atypical vessel formation where the previous regularity in the blood vessels (punctation and mosaic) now becomes extreme in structure and adopts a marked irregularity, usually is indicative of possibly early invasive cancer (microinvasion).

• The accuracy of colposcopy: how can we make it better?
  C. Redman (UK)
  

A fundamental role of activity in women with abnormal screening results is to make an accurate assessment of the cervix.  A number of studies, both cross-sectional and prospective, indicate that whilst colposcopic performance compares favourably with other diagnostic tests, it lacks sensitivity and specificity. It is evident that that a number of factors have to be considered: the number of biopsies taken, the prevalence of high grade disease in group being studied and the quality of training. These aspects are reviewed and strategies to improve performance are discussed.

• The value of biomarkers in colposcopy practice
  C. Bergeron (France)
  

P16 immunohistochemistry is the most widely enlisted biomarker in the uterine cervix and in the HPV-related neoplasia in general. Biologically highgrade lesions, e.g. true precancers are virtually always p16 positive. The LAST recommendations therefore advocate for p16 application in all cases of suspected CIN2 as a way of minimizing CIN2 cases as well as cases with a differential diagnosis of CIN3 vs. benign (atrophy, squamous metaplasia, etc.). Although the diagnostic value of p16 immunohistochemistry in the uterine cervix is well-established in these scenarios, p16 falters when it comes to prognostication and is not considered a reliable prognostic marker in LSIL histological cases.

Using a combination of antibodies to detect p16 and the cell cycle marker Ki67 identifies HPV-transformed cervical cells. The clinical performance of this approach has been evaluated in the triage of ASC-US and LSIL cytology results and more recently in HPV-primary screening. Cytology informed of HPV positivity is more expected to perform better than predicted by trials and could possibly allow longer intervals before retesting HPV-positive women with normal cytology.  Alternative triage strategies like combining genotyping (16/18 only vs extended genotyping) with cytology, p16/ki67 dual stain ICC or methylation analyses are all under active evaluation for optimization of the balance between immediate referral vs deferred assessment of HPV positive women sensitive than blind cytology. Screening programs with informed cytology triage are expected to perform better than predicted by trials and could possibly allow longer intervals before retesting HPV-positive women with normal cytology.  Alternative triage strategies like combining genotyping (16/18 only vs extended genotyping) with cytology, p16/ki67 dual stain ICC or methylation analyses are all under active evaluation for optimization of the balance between immediate referral vs deferred assessment of HPV positive women.

• Towards the safe and accurate treatment of cervical precancer
  C. Redman (UK)

Local cervical treatment in women with suspected cervical precancer is relatively easy to do but can have appreciable morbidity, especially on both future childbearing and the ability to accurately perform adequate follow-up tests. It is important that colposcopists consider when treatment is needed and how it can be undertaken in such a way as to be effective but avoid over-treatment. This encompasses issues such as depth of excision, avoidance of needless treatment especially in younger women whose cervical disease may be self-limiting. These issues will be addressed on the basis of extant evidence with recommendations for safe practice.