Cervical Squamous Cell Carcinoma

Excerpt

Cervical cancer is the cancer of the female reproductive system that originates in the cervix. It is the fourth leading cause of cancer in women after breast, lung, and colorectal cancer. It is easily preventable, owing to the universal application of Papanicolaou smear screening that has resulted in the early detection of pre-cancerous lesions, which can be removed before it progresses to invasive cancer. However, it is still a common genital cancer encountered in clinical practice in women of low and middle-income countries (LMICs) due to a lack of extensive screening. Cervical cancers are often squamous-cell carcinomas that arise from infection with high-risk Human Papilloma Virus (HPV) serotype-16 and 18.

Anatomy Of Cervix

1. Embryology: The cervix along with fallopian tubes, the body of the uterus, and the upper third of the vagina are all derived from the paramesonephric duct.

2. Gross Structure: Cervix is the lowermost cylindrical part of the uterus in females measuring about 2.5 cm in length. The interior cavity of the cervix is called the cervical canal. The cervical canal communicates above with the cavity of the body of the uterus through the internal os and below with the vaginal cavity through the external os. The lower part of the cervix projects into the anterior vaginal wall, which divides it into a supravaginal part and a vaginal part. The supravaginal part is related anteriorly to the bladder, posteriorly to the rectovaginal pouch (containing intestines) and rectum, and on either side to the ureter and uterine artery embedded in the parametrium. The space between the vaginal part of the cervix and the vagina forms the vaginal fornices.

3. Microscopic Anatomy: The cervix is composed mainly of fibroelastic connective tissue. It can be divided into endocervix, cervical transformation zone, and ectocervix. The endocervix is composed of simple columnar epithelium, which produces mucus and the ectocervix is composed of non-keratinized stratified squamous epithelium. The cervical transformation zone or the squamocolumnar junction represents the zone where the columnar epithelium of the endocervix changes to the squamous epithelium of the ectocervix. Cervical cancer mostly originates from this region.

4. Vasculature: Uterine artery.

5. Lymphatics: External iliac, internal iliac, obturator, and sacral lymph nodes.

6. Innervation: Sympathetic from T12 - L2 (contraction and vasoconstriction); parasympathetic from S2 - S4 (vasodilation) and viscerosensory fibers (pain sensations) passes along parasympathetic nerves.

Natural History And Pattern Of Spread

Cervical cancer incidence has dramatically declined in regions where screening programs have been implemented. About 70 percent of the current burden of cervical cancer comes from the low-socioeconomic areas where screening programs are not well-established. Cervical cancer is most common in females who have multiple sexual partners and do not use condoms. High-risk sexual practices result in infection by the HPV. HPV integrates its DNA into the basal cells of the columnar junction (in the transformation zone of the cervix), and this results in the production of proteins (E6 and E7) that eventually cause dysplasia. Dysplasia of the cervical epithelium is also called cervical intraepithelial neoplasia(CIN). While CIN can progress to cervical cancer regression can take place. Rates of progression to cancer vary in different studies.

CIN does not necessarily develop in all women who get infected with HPV. The immune system clears off most of the HPV infection. The risk of CIN increases with the type of HPV (HPV 6 and 11 are low-risk types, whereas 16 and 18 are high-risk types), duration of infection, environmental factors like smoking, and immunosuppression in the patient. Fortunately, vaccination against HPV is available, which immunizes against several HPV types linked with cervical cancer, including HPV 16. As compared to other gynecological cancer, cervical cancer occurs in younger women.

The mean age of diagnosis of cervical cancer is about 49 years. Most of these women will be diagnosed with early-stage cancer and cured, though they might have to carry the burden of potential treatment-related side effects(e.g., infertility). The majority of the women who are cervical cancer survivors are diagnosed with early-stage or locally advanced cancer. The median survival of women diagnosed with metastatic or recurrent cervical cancer is generally less than two years. The most common areas of metastases from cervical cancer are the lymph nodes, liver, lungs, and bones.