To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Columbia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0-66.7); SH OR = 6.8 (3.4-13.4); and PCR OR = 28.8 (15.7-52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal.

The causal link between human papillomavirus and invasive cervical cancer: A population-based case-control study in colombia and spain

Despite international agreements and national laws, marriage of girls <18 years of age is common worldwide and affects millions. Child marriage is a human rights violation that prevents girls from obtaining an education, enjoying optimal health, bonding with others their own age, maturing, and ultimately choosing their own life partners. Child marriage is driven by poverty and has many effects on girls' health: increased risk for sexually transmitted diseases, cervical cancer, malaria, death during childbirth, and obstetric fistulas. Girls' offspring are at increased risk for premature birth and death as neonates, infants, or children. To stop child marriage, policies and programs must educate communities, raise awareness, engage local and religious leaders, involve parents, and empower girls through education and employment.

Health consequences of child marriage in Africa.

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.

The epidemiology of cervical carcinogenesis.

Re-establishment of the cancer registry in Kyadondo County, Uganda, has allowed estimation of incidence rates for the period September 1989 to December 1991. The results are compared with earlier data from the same area, and from other African cancer registries. The most striking feature is the emergence of Kaposi's sarcoma as the leading cancer in males (almost half of all registered cases) and the second most frequent (17.9%) in females. This parallels the evolution of the epidemic of AIDS. There were also marked increases in the incidence of both oesophageal and prostatic carcinoma, while the incidence of cancer of the penis and the urinary bladder declined, possibly as a result of improved standards of hygiene. In females, the incidence of cancer of the cervix has more than doubled since the 1950s, and is now among the highest recorded in the African continent.

Cancer in Kampala, Uganda, in 1989–91: Changes in incidence in the era of aids

A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.

Risk factors for cervical cancer in Colombia and Spain

The presence of several infections was determined in tissue and serum samples from 34 cases and 23 controls seen in 1984-85 at Mulago Hospital in Kampala, Uganda. When assessing single infections, association with cervical cancer could be shown for 5 agents, namely by Southern blot assay for human papillomavirus types 16 and 18 (HPV), and by serological tests at varying levels of antibody titres, for herpes simplex virus type I and/or 2 (HSV), cytomegalovirus (CMV), Epstein-Barr virus, viral capsid antigen (EBV-VCA), and Chlamydia trachomatis (CLT). Due to interaction, HSV and CMV were associated with cervical cancer only when infection by both of these agents was demonstrable. In the assessment of the simultaneous presence of these 5 infections, moderately high antibody titres were taken as the cut-off point for infection by HSV, CMV, EBV-VCA, and CLT. This showed that 3 and 4 infections at a time were seen in the majority of the cases in contrast to the controls with essentially no more than 2 such infections. A linear trend in the rise of risk for cervical cancer was noted with increasing number of infections.

P. Okong

Papers

Multiple infections in cases of cervical cancer from a high-incidence area in tropical Africa.