Human papillomavirus the main risk factor for cervical adenocarcinoma

Human papillomavirus (HPV) was found to be the main risk factor associated with increased incidence of an unusual type of cervical cancer called cervical adenocarcinoma, according to a study in the March 1 issue of the Journal of the National Cancer Institute.

The incidence of cervical adenocarcinoma has increased in recent years, even in countries with widespread screening programs, with incidence doubling in relation to all other cervical cancers between 1973 and 1996. HPV is a well-established cause of cervical squamous cell cancer, the most common type of cervical cancer worldwide. Previous studies have suggested HPV may also cause cervical adenocarcinoma, but those studies were small and did not provide information on the role of other factors in the development of this cancer.

To investigate the links between HPV and cervical adenocarcinoma in a multicenter, international sample of women, Xavier Castellsague, M.D., at the Institut Catala d'Oncologia in Barcelona, Spain, and colleagues conducted a pooled analysis of eight case-control studies of cervical cancer conducted in countries in Africa, South America, and Southeast Asia. Women had been interviewed to determine potential risk factors for cervical cancer, and all received a pelvic examination as well as testing for HPV and cervical cancer.

Castellsague and colleages found that HPV infection was associated with an 80-fold increase in the risk of cervical adenocarcinoma in the populations studied. Additional risk factors for cervical adenocarcinoma among HPV-positive women included poor hygiene, long-term use of hormonal contraceptives, no schooling, sexual behavior-related variables, and infection with herpes simplex virus 2 (HSV-2). The most common HPV types in women with cervical adenocarcinoma were HPV 16 and 18, which are also the most common types in women who develop the more common type of cervical cancer, squamous cell carcinoma.

The authors suggest that these findings have direct implications for cervical cancer prevention and control. On the basis of the data from this study, they estimated that the two currently most widely tested HPV vaccines, which are designed to prevent infection by HPV 16 and 18, have the potential to prevent up to 86% of all cervical adenocarcinomas worldwide.

"This multi-center study demonstrates the existence of a consistent, strong and robust increased association between infection by high-risk HPV types and risk of development of adenocarcinoma," the authors write.

In an accompanying editorial, Allan Hildesheim, Ph.D., of the National Cancer Institute, and Amy Berrington, D.Phil., of Johns Hopkins University, write, "Despite increases in [adenocarcinoma] rates in recent decades, it would not be unrealistic to expect rates of [adenocarcinoma] to drop in future years, as screening continues to be improved, HPV testing is incorporated into (or in some instances replaces) Pap smear screening programs, and prophylactic HPV16/18 vaccines become available for broad use. The new challenge facing policymakers and the public health community at large is to use the various tools now at our disposal to reduce disease burden associated with [squamous cell carcinoma] and [adenocarcinoma] in the broadest, most rational, and cost-effective manner."