Chapter 1: Histopathology of gynaecological cancers
Uterine cervix tumours
Cervical neoplasia pertains primarily to epithelial tumours, including SCC, adenocarcinoma and neuroendocrine carcinoma; other entities are rare.
Glandular precursors and invasive tumours are divided into human papillomavirus (HPV)-associated and HPV-independent entities; squamous tumours are almost universally HPV-associated (Figure 1.16).
Figure 1.16: WHO 2014 and IECC 2018 classifications of cervical adenocarcinomas*
Abbreviations: HPV, human papillomavirus; IECC, International Endocervical Adenocarcinoma Criteria and Classification; NOS, not otherwise specified; WHO, World Health Organization.
*The 5th edition of the WHO Classification of Female Genital Tumours (2020) has incorporated the 2018 IECC system for endocervical adenocarcinomas, as well as the Silva pattern-based classification.
Credit: Park KJ. Histopathology 2020;76:112-127.
Immunostaining for p16 is a surrogate marker of HPV infection, although there is not full concordance between HPV molecular typing and p16 staining.
Squamous cell neoplasia: low- and high-grade squamous intraepithelial lesions (LSIL, HSIL) are precursors of SCC; the latter is associated with a higher risk of progression.
HPV16 is the most commonly found virus type, and is associated with the highest risk of transformation, occurring via integration of the E6 and E7 viral genes and deactivation of p53 and retinoblastoma (Rb), respectively.
The majority of SCCs are focally- or non-keratinising; grading is not informative of prognosis (Figure 1.17).
Figure 1.17: HSIL/CIN3 and invasive squamous cell carcinoma
Abbreviations: HSIL, high-grade squamous intraepithelial lesion.
Credit: Courtesy of the authors
Columnar cell neoplasia: HPV-associated adenocarcinomas constitute 80% of cervical adenocarcinomas and develop from adenocarcinoma in situ (AIS); HPV16 and HPV18 are the most commonly found virus types (Figure 1.18).
Figure 1.18: HPV-associated adenocarcinoma
Abbreviations: HPV, human papillomavirus.
Credit: Courtesy of the authors
A grading of HPV-associated adenocarcinoma based on architecture and stromal response (the Silva classification) has been proposed.
The most common HPV-independent adenocarcinoma is of gastric type; these tumours often have aberrant p53 staining and worse stage-matched prognosis compared with HPV-associated tumours.
Revision Questions
- Which malignant tumours are most common in the cervix?
- Which tumours are classified based on HPV status?
- What type of HPV-independent adenocarcinoma is the most common?
