Human papillomavirus and cancer: the epidemiological evidence

doi:10.1016/S1386-6532(00)00125-6

Journal of Clinical Virology

Volume 19, Issues 1–2, October 2000, Pages 1-5

https://doi.org/10.1016/S1386-6532(00)00125-6 Get rights and content

Abstract

Objective: Summary of the studies carried out by the IARC on HPV and cervical cancer is presented. Results: the first one was the international prevalence survey of HPV types in invasive cervical cancer (ICC) conducted in up to 22 countries. Overall, 99.7% of 1000 cases with histologically confirmed ICC were also shown to be HPV DNA positive using the GP5+/GP6+ or E7 primers, indicating that HPV is a necessary cause of cervical cancer. The most prevalent HPV types were HPV 16 (53%), HPV 18 (15%), HPV 45 (9%), HPV 31 (6%) and HPV 33 (3%). HPV 16 was the most common type in all geographical regions, followed by HPV 18 that was particularly, common in South–East Asia. The second set of studies included case-control studies carried out in 13 countries. They included about 2000 cases and 2000 controls. Positivity, for any HPV DNA yielded a pooled odds ratio (OR) of 70. The association was equally strong for both squamous cell (OR=74) and adenocarcinoma (OR=50) and for HPV 16 and 18 as well as for the less common HPV types. Our results indicate that in addition to HPV 16 and 18, HPV 31, 33, 35, 45, 51, 52, 58 and 59 now can be considered as carcinogenic. The third group of studies is aimed to determine the HPV DNA prevalence in random, age-stratified (by 5 years, 15–19 to 65+) subsamples (1100 women) of the general population. Two age-peaks (<25 and >59 years), have been found in some countries (Costa-Rica, Mexico, Colombia) but not in all (Argentina). Whether the second peak is due to viral reactivation, variations in screening or represents a birth-cohort effect remains to be determined. The distribution of the most prevalent HPV types in the general population (HPV 16, 18, 45, 31, 58, 33, 35) resembles that for cervical cancer cases. Conclusions: our studies provide the most solid epidemiological evidence, to conclude that HPV is not only the central cause of cervical cancer worldwide but also a necessary cause.

Introduction

Certain types of human papillomavirus (HPV) are recognized today as human carcinogens. In 1995, the International Agency for Research on Cancer (IARC) evaluated all relevant data on the carcinogenicity of HPV and concluded that there was sufficient evidence to categorize HPV types 16 and 18 as human carcinogens, but that the existing evidence was limited or inadequate for the other HPV types (IARC, 1995). Since the IARC evaluation, we have completed case-control studies on cervical cancer in various populations. There have also been several studies linking these viruses to other ano-genital tumours and cancers of other sites.

In the following, I will briefly summarize these studies. First, the old international survey on invasive cervical cancer with a recent update, then the series of multi-centre case-control studies that we have been doing in various countries, and finally, international prevalence surveys of HPV in general population.

Section snippets

HPV and cervical cancer

There is no doubt that infection with certain types of HPV is the main cause of cervical cancer (IARC, 1995). The next question, we will have to answer will be: is this infection a necessary and sufficient cause of cervical cancer? To address the first part of this question, we have retested the specimens originally categorized as HPV-negative in the IARC international prevalence survey of HPV DNA in invasive cervical cancer (Bosch et al., 1995). Over 1000 frozen biopsy specimens were collected

Case-control studies

The second set of multi-centre studies that the IARC has conducted, are the case-control studies on invasive cervical cancer first in collaboration with Keerti Shah's lab for the Spain–Colombia studies, and later with Jan Walboomers’ lab. What we wanted to do in these case-control studies was to assess the risk associated to the various HPV types and also to assess the role of co-factors.

We have conducted 13 case-control studies, 11 of them are hospital based, again in many areas of the world.

Population surveys

We are involved in cohort studies with in Costa Rica and Colombia. In Colombia, we are following a cohort of 2000 women in the age-group 30–69. These women were recruited from four areas in Bogota. They are being interviewed with a very detailed questionnaire on risk factors for cervical cancer. We are collecting cervical scrapes and blood samples from them, and they are being followed every 6–9 months. At each follow-up visit we interview them with a short questionnaire and collect the

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Human papillomavirus and cancer: the epidemiological evidence

Abstract

Introduction

Section snippets

HPV and cervical cancer

Case-control studies

Population surveys

Prevalence of human papillomavirus in cervical cancer: a worldwide perspective

J. Natl. Cancer Inst.

The viral origin of cervical cancer in Rabat, Morocco

Int. J. Cancer

Risk factors for cervical cancer in Thailand: a case-control study

J. Natl. Cancer Inst.

Human papillomavirus and invasive cervical cancer in Brazil

Br. J. Cancer

A population-based study of all grades of cervical neoplasia in rural Costa Rica

J. Natl. Cancer Inst.