**2. Anatomy and pathology**

The cervix is the lower portion of the uterus that joins the corpus to the vagina (from the Latin collar, "neck"). The exocervix, also referred to as the ectocervix, protrudes into the top vagina and is protected with squamous epithelium. The canal that connects to the endometrial hollow space is the endocervix. It has a single layer of mucinous columnar cells and longitudinal mucosal ridges consisting of fibrovascular cores. The macroscopic intersection of the exocervix and endocervix is known as the external os. The microscopic connection of the mucous and squamous, columnar epithelia is called the squamocolumnar junction. The isthmus also referred to as the decreased uterine phase, is the area between the endocervix and the endometrial hollow space [6].

The transformation sector is the region among the most distal squamocolumnar juncture and the external os. This quarter's immature squamous epithelium exhibits progressive nuclear maturation and increases the glycogen-loose cytoplasm closer to the surface. Colposcopy has a thin white membrane that thickens and turns white as the squamous epithelium grows. As cells collect glycogen, they become indistinguishable from the typical exocervical squamous epithelium. The transformation zone is where cervical squamous cancers mainly develop [6]. The classification of cervical epithelial alterations according to their histological characteristics differentiates groups of women based on the state of cellular maturation, and the thickness of the affected area in the squamous epithelium is presented in **Table 1**.

The Bethesda system divides cytological specimens into two main groups, lowgrade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs) [7]. LSILs are characterized by modifications in mature squamous cells (superficial or intermediate) because of HPV, and the morphological modifications are identical to slight dysplasia or low-grade intraepithelial lesion (NIC1). The possibility of growing a high-grade intraepithelial lesion or most cancers over 5 years is 18% [8]. HSILs are characterized by losing the nucleus-to-cytoplasm ratio in the tiniest, maximum juvenile squamous cells (para-basal). This is the primary indicator of the pathology. The presence of NIC2, NIC3, and in situ most cancers in the histological section is all additives of an HSIL analysis in cytology. A NIC2 or NIC3 biopsy is carried out on most patients who have been diagnosed with HSIL [9]. Squamous cell carcinoma is an epithelial invasive tumor constructed from differentiated squamous cells. The Bethesda system does not subdivide squamous cell carcinoma in the same manner as the WHO category system. Keratinizing, nonkeratinizing, papillary, basaloid, warty, squamous-transitional, and lymphoepithelial are the classifications used by the WHO (**Table 2**). This is because morphological developments cannot be outstanding through cytology information. Atypical glandular cells (AHCs) refer to abnormalities in the glandular epithelium that go beyond

#### **Specimen adequacy**

Satisfactory for evaluation (*note presence/absence of endocervical/transformation zone component*) Unsatisfactory for evaluation … (*specify reason*). Specimen rejected/not processed (*specify reason*) Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (*specify reason*) **General categorization (***optional***)** Negative for intraepithelial lesion or malignancy epithelial cell abnormality Other **Interpretation/result Negative for intraepithelial lesion or malignancy** Organisms *Trichomonas vaginalis* Fungal organisms morphologically consistent with *Candida* species shift in flora suggestive of bacterial vaginosis Bacteria morphologically consistent with *Actinomyces* species cellular changes consistent with herpes simplex virus Other non-neoplastic findings (*optional to report; list not comprehensive*) Reactive cellular changes associated with inflammation (includes typical repair) radiation Intrauterine contraceptive device glandular cells status post hysterectomy atrophy **Epithelial cell abnormalities** Squamous cell Atypical squamous cells (ASC) of undetermined significance (ASC-US) cannot exclude HSIL (ASC-H) Low-grade squamous intraepithelial lesion (LSIL) encompassing: human papillomavirus/mild dysplasia/ cervical intraepithelial neoplasia (CIN) 1 High-grade squamous intraepithelial lesion (HSIL) encompassing: moderate and severe dysplasia, carcinoma in situ; CIN 2 and CIN 3 Squamous cell carcinoma glandular cell Atypical glandular cells (AGC) (*specify endocervical, endometrial, or not otherwise specified*) Atypical glandular cells, favor neoplastic (*specify endocervical or not otherwise specified*) Endocervical adenocarcinoma in situ (AIS) adenocarcinoma **Other** (*List not comprehensive*) Endometrial cells in a woman S40 years of age

#### **Table 1.**

*The 2001 Bethesda System (Abridged).*

#### **Squamous epithelial tumors**

	- Squamous metaplasia
	- Atrophy of the uterine cervix
	- Condyloma acuminatum
	- Squamous intraepithelial lesions of the uterine cervix
	- Squamous cell carcinoma, HPV associated, of the uterine cervix
	- Squamous cell carcinoma, HPV independent, of the uterine cervix
	- Squamous cell carcinoma, NOS of the uterine cervix

#### **Glandular tumors and precursors**

	- Endocervical polyp
	- Müllerian papilloma of the uterine cervix
	- Nabothian cyst
	- Tunnel clusters
	- Microglandular hyperplasia
	- Lobular endocervical glandular hyperplasia
	- Diffuse laminar endocervical hyperplasia
	- Mesonephric remnants and hyperplasia
	- Arias Stella reaction of the uterine cervix
	- Endocervicosis of the uterine cervix


◦ Germ cell tumors of the uterine cervix

#### **Table 2.**

*The World Health Organization classification of tumors cervix, 5th edition (2020).*

reactive changes but are insufficient to classify them as adenocarcinoma. The morphological entities that advise this prognosis may be benign or malignant. The benign conditions include endocervical and endometrial polyps, endometriosis, endocervical microcystic hyperplasia, adenosis, lively and lower uterine phase brushings, tubal metaplasia, and Arias-Stella phenomenon. Malignant situations include high-grade intraepithelial lesions with glandular penetration, in situ adenocarcinoma, and invasive adenocarcinoma [10].

Other pathological types of cervical cancer include endometrioid adenocarcinoma, clear cell adenocarcinoma, adenosquamous carcinoma, adenoid cystic carcinoma, adenoid basal cell carcinoma, small cell carcinoma, neuroendocrine carcinoma, and undifferentiated carcinoma.

Squamous cell carcinomas arise between 80 and 90% of all cervical cancers. Those designations no longer correspond correctly with analysis, despite the reality that squamous neoplasms are often sub-classified as large-cell keratinizing, huge-cellular no keratinizing, or small-cellular carcinomas [11]. It is estimated that between 10 and 20% of women may develop primary cervical adenocarcinoma throughout their lifetimes, although the incidence of this cancer appears to be on the rise, particularly in younger females [12].
