The epidemiology of cervical carcinogenesis

Abstract

Epidemiologic and laboratory data suggest that cervical cancer typically arises from a series of causal steps. Each step can be studied separately in the hope of better etiologic understanding and improved cancer prevention. The earliest identified etiologic step is infection of young women with specific types of venereally transmissible human papillomaviruses (HPVs). Cervical HPV infections often lead to low grade squamous intraepithelial lesions (mildly abnormal Pap smears). Human papillomavirus infections and their associated lesions are extremely common among young, sexually active women. The infections typically resolve spontaneously even at the molecular level within months to a few years. Uncommonly, HPV infections and/or low grade lesions persist and progress to high grade lesions. The risk factors for progression are mainly unknown but include HPV type and intensity, cell‐mediated immunity, and reproductive factors. Nutritional factors or co‐infection with other pathogens may also be involved at this apparently critical etiologic step between common low grade and uncommon high grade intraepithelial lesions. Except for advancing age, no epidemiologic risk factors have been found for the next step between high grade intraepithelial lesions and invasive cancer. At the molecular level, invasion is associated with integration of viral DNA. Based on worldwide research, the steps in cervical carcinogenesis appear to be fundamentally the same everywhere, with a central role for HPV infection. The importance of etiologic cofactors like smoking, however, may vary by region. Cancer 1995; 76:1888–901.

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection

“…Causal models that have been proposed are trauma to the cervix or hormonal effects (Schiffman and Brinton, 1995). Since very few women in our study were multiparous, we investigated a possible effect of pregnancy.…”

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

“…1 Infection by highrisk human papillomavirus (HPV) is a major cause of CACX 2 along with other etiological factors, such as use of oral contraceptives, precocious marriage, multiparity and smoking. 1,3 As HPV infections in most cases do not lead to cancer, and even a long latency period for the cancerous outcome in infected women suggests involvement of additional genetic alterations like functional inactivation of tumor suppressor genes (TSGs) or activation of oncogenes. 4 Investigations showing frequent chromosomal deletion in 11q23-q24 (20.4 Mb) in cervix, 5-7 breast, 8,9 lung, 10 colon 11 and ovarian 12 cancer and functional chromosome-transfer…”

Human papillomavirus infection in Rio de Janeiro, Brazil: a retrospective study

“…But neither research assays nor commercial kits (dot blot or in situ hybridization) have been found to be adequate for clinical use. An assay for routine clinical use requires reliable and accurate detection of the broad range of pathogenic HPV types that infect the genital tract [5].…”

“…In many developing countries, it is still the main cause of death from cancer in women [5]. High annual cancer incidences have been reported in Brazil.…”