Invasive squamous cell carcinoma of the cervix: A review of morphological appearances encountered in human papillomavirus-associated and papillomavirus-independent tumors and precursor lesions Review


Authors: Stolnicu, S.; Allison, D.; Patrichi, A.; Flynn, J.; Iasonos, A.; Soslow, R. A.
Review Title: Invasive squamous cell carcinoma of the cervix: A review of morphological appearances encountered in human papillomavirus-associated and papillomavirus-independent tumors and precursor lesions
Abstract: Cervical cancer is the fourth most common cancer among women globally. Historically, human papillomavirus (HPV) infection was considered necessary for the development of both precursor and invasive epithelial tumors of the cervix; however, studies in the last decade have shown that a significant proportion of cervical carcinomas are HPV-independent (HPVI). The 2020 World Health Organization (WHO) Classification of Female Genital Tumors separates both squamous cell carcinomas (SCCs) and endocervical adenocarcinomas (ECAs) by HPV status into HPV-associated (HPVA) and HPVI tumors. The classification further indicates that, in contrast to endocervical adenocarcinomas, HPVI and HPVA SCCs cannot be distinguished by morphological criteria alone and suggests that HPV testing or correlates thereof are required for correct classification. Moreover, while HPVA SCC precursor lesions (ie, high-grade squamous intraepithelial lesion) are well known and characterized, precursors to HPVI SCCs have only been described recently in a small number of cases. We studied 670 cases of SCCs from the International Squamous Cell Carcinoma Project (ISCCP) to analyze the reproducibility of recognition of invasive SCC growth patterns, presence of lymphovascular space invasion, tumor grade, and associations with patient outcomes. Consistent with previous studies, we found histologic growth patterns and tumor types had limited prognostic implications. In addition, we describe the wide morphologic spectrum of HPVA and HPVI SCCs and their precursor lesions, including tumor growth patterns, particular and peculiar morphologic features that can lead to differential diagnoses, and the role of ancillary studies in the diagnosis of these tumors. © 2024 Lippincott Williams and Wilkins. All rights reserved.
Keywords: review; squamous cell carcinoma; carcinoma, squamous cell; cancer grading; adenocarcinoma; reproducibility; reproducibility of results; cytology; consensus; differential diagnosis; pathology; histology; morphology; world health organization; tumor growth; uterine cervical neoplasms; epithelium tumor; uterine cervix tumor; uterine cervix; cervical cancer; cervix uteri; wart virus; papillomavirus infections; human papillomavirus; papillomavirus infection; precursor lesions; keratinization; papillomaviridae; humans; human; female; endocervical adenocarcinoma; cervical squamous cell carcinoma; human papillomavirus viruses; human papillomavirus associated tumor; human papillomavirus independent tumor; precursor human papillomavirus associated lesion
Journal Title: Advances in Anatomic Pathology
Volume: 31
Issue: 1
ISSN: 1072-4109
Publisher: Lippincott Williams & Wilkins  
Date Published: 2024-01-01
Language: English
DOI: 10.1097/pap.0000000000000411
PUBMED: 37638549
PROVIDER: scopus
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus
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MSK Authors
  1. Alexia Elia Iasonos
    363 Iasonos
  2. Jessica Flynn
    182 Flynn