Etiology

Human papillomavirus (HPV) infection is the most important etiologic factor, with most (99.7%) tumors containing HPV DNA.[24] HPV infection is spread by skin-to-skin sexual contact. HPV-16 and 18 are the most common high-risk types detected in more than 70% of malignancies. Other high-risk types include 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82.[25][26]

Peak infection incidence in females is in the late teens and early 20s, but in 90% of patients in this age group, the infection resolves within 2 years (with clearance typically occurring 6 months after infection).[27][28][29] Once infection resolves, the risk of cervical cancer returns to baseline.

Cervical cancer in the absence of demonstrable HPV infection does occur, but it is extremely rare, and HPV testing appears to be more sensitive than and superior to standard cervical screening.[30]

Pathophysiology

The incubation from latent infection to presentation with cancer is typically 15 years.[31] The oncoproteins E6 (which binds p53) and E7 (which interacts with retinoblastoma protein Rb), in conjunction with co-factors yet to be defined, drive cervical intraepithelial neoplasia as a monoclonal proliferation (by loss of E2F cell cycle regulation) to invasive cancer.[32][33]

Classification

Histopathologic subtypes[1]

Squamous epithelial tumors

  • Mimics of squamous precursor lesions

    • Squamous metaplasia

    • Atrophy of the uterine cervix.

  • Squamous cell tumors and precursors

    • Condyloma acuminatum

    • Squamous intraepithelial lesions of the uterine cervix

    • Human papillomavirus (HPV)-associated squamous cell carcinoma (SCC) of the cervix

    • HPV independent SCC of the cervix

    • SCC NOS of the cervix.

Glandular tumors and precursors

  • Benign glandular lesions

    • Endocervical polyp

    • Mullerian papilloma

    • Nabothian cyst

    • Microglandular hyperplasia

    • Lobular endocervical glandular hyperplasia

    • Diffuse laminar endocervical hyperplasia

    • Mesonephric remnants and hyperplasia

    • Arias-Stella reaction of the cervix

    • Endocervicosis of the cervix

    • Tuboendometrioid metaplasia

    • Ectopic prostate tissue.

  • Adenocarcinomas

    • HPV-associated adenocarcinoma in situ

    • HPV-associated adenocarcinoma of the cervix

    • HPV-independent adenocarcinoma in situ

    • HPV-independent gastric type adenocarcinoma

    • HPV-independent clear cell type adenocarcinoma

    • HPV-independent mesonephric type adenocarcinoma

    • Other adenocarcinomas of the cervix.

Other epithelial tumors

  • Carcinoma of the uterine cervix

  • Adenosquamous and mucoepidermoid carcinomas of the uterine cervix

  • Adenoid basal carcinoma of the uterine cervix

  • Carcinoma of the uterine cervix, unclassifiable.

Mixed epithelial and mesenchymal tumors

  • Adenomyoma of the uterine cervix

  • Adenosarcoma of the uterine cervix.

Germ cell tumors

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