Topics of Histopathology and Cytology of Cervical Cancer and Screening

The vast majority of cervical cancers are carcinomas (99.6%)—mainly, squamous cell carcinomas (SCC) and adenocarcinomas, and very minor tumors are sarcomas (0.4%) (Acta Obstet Gynaecol Jpn 74:2345–402, 2022). SCCs are three times more common than adenocarcinomas (Acta Obstet Gynaecol Jpn 74:2345–402, 2022). Cervical cancer is the fourth most common cancer among women worldwide, after breast, colorectal, and lung cancers (Herrington et al WHO classification of tumours. Female genital tumours, Lyon, IARC Press, 2020). In Japan, cervical cancer was the 12th most common cause of death (CANCER STATISTICS IN JAPAN, 2022. https://ganjoho.jp/public/qa_links/report/statistics/2022_en.html ). According to the 2020 World Health Organization (WHO) tumor classification, cervical SCCs and adenocarcinomas have been categorized as HPV (human papillomavirus)-associated and HPV-independent cancers. Almost all cervical SCCs are HPV-associated, and a few SCCs have been reported to be HPV-independent (Casey et al Int J Gynecol Pathol 34:208–12, 2015). Although it is recommended that whether SCC is HPV-associated or HPV-independent be documented in the pathological report, there is currently no stratification in the treatment strategy between HPV-associated and HPV-independent carcinoma. A histological diagnosis of SCC—NOS without differentiating between the two categories can be an acceptable alternative. Distinguishing between HPV-associated SCC and HPV-independent SCC is difficult based only on histologic findings; it usually requires p16 immunostaining, HPV in situ hybridization, or HPV testing. In contrast to SCCs, adenocarcinomas, whether in situ or invasive, are relatively easy to categorize as HPV-associated and HPV-independent based on histology. In this revision of the WHO classification, some minor variants such as adenoid cystic carcinoma and ground-glass carcinoma have been deleted. Adenoid cystic carcinoma is now considered a variant of HPV-associated adenocarcinoma, and ground-glass carcinoma is included in poorly differentiated adenosquamous carcinoma because of undefined diagnostic criteria. In Chap. 11 , uterine neuroendocrine tumors and carcinomas in both the cervix and body are independently categorized as follows: neuroendocrine tumor, grade 1; neuroendocrine tumor, grade 2; small cell neuroendocrine carcinoma; large cell neuroendocrine carcinoma; combined small cell neuroendocrine carcinoma; and combined large cell neuroendocrine carcinoma. The low- and high-grade tumor terminologies were deleted. The cytology of cervical cancers and their precursors has been thoroughly established based on the 2001 version of the Bethesda System, which was developed in combination with HPV testing for the triage of precursors in the 2014 version. Cytological terminologies such as squamous intraepithelial lesions (SIL) are being used as histologic terminologies along with cervical intraepithelial lesions (CIN) in the 2014 WHO tumor classification (Stoler et al WHO classification of tumours. Female genital tumours, Lyon, IARC Press, 2014).