Women who harbor multiple HPV type infections are at higher risk for cervical lesions

The risk for developing the tissue abnormalities, or lesions, that typically precede cervical cancer is much higher for women infected with multiple genotypes of the human papillomavirus (HPV) than previously reported, according to a study published in the July issue of Cancer Epidemiology, Biomarkers & Prevention.

Although doctors have known that the cervical tissue at the opening to the womb can harbor multiple HPV types, this study is the first to document that the risk for developing cervical cancer, the second most common form of cancer in women worldwide, is higher in females infected with multiple HPV types than those infected with just one HPV type.

In addition, the study's findings provide baseline data for analyzing over time the impact of the newly approved vaccine, Gardasil, on the dynamics of HPV infection.

"Women who harbor multiple infections are at higher risk for cervical lesions than those ever infected with one type only and should be followed more closely," said Eduardo L. Franco, Dr.PH., leader of the study and professor of epidemiology and oncology, and director, division of cancer epidemiology at McGill University.

Like previous studies on HPV in cervical cancer, the new research found that pre-cancerous abnormalities primarily occurred in women infected with HPV 16 and 18, the targets of Gardasil.

The vaccine also will prevent infection by the HPV types 6 and 11 that are associated with genital warts, and thus is expected to prevent cervical cancer in thousands of women.

However, the vaccine will not protect against HPV 58, which the new study discovered to be far more oncogenic than others when found in co-infections with other HPV types. The study's findings suggest HPV 58 should be one of the targets of the next generation of cervical cancer vaccines.

Indeed, the scientists discovered that the higher risk associated with HPV 58 in co-infections was similar to that conferred by HPV 16 in co-infections. Both HPV 58 and 16 "seemed particularly prone to increase risk" for pre-cancerous lesions in the cervix, said Helen Trottier, Ph.D., the first author of the research paper.

Participating in the study were 2,000 women, ages 18 to 40, most of whom were Caucasian and lived in Brazil. The team of scientists who conducted the study is based at McGill University in Canada and the Ludwig Institute for Cancer Research in Brazil.

The results suggest that the current method that doctors use for HPV screenings - the Papanicolaou cytology or "pap smear" - should be replaced with a test that detects the presence of a HPV co-infection and identifies each HPV genotype. If an infection is present, the current test cannot determine whether it was triggered by just one genotype or multiple types of HPV.

Because the HPV test used by Franco and his colleagues could detect more than 40 types of the virus and the presence of multiple infections, they could determine the specific genotypes of HPV present in the women's cervical tissue in single infections as well as co-infections.

The scientists theorized that the multiple viral infections could act synergistically to increase the pre-cancerous mutations or to expedite their progression to cancer. They also suggest that the presence of HPV co-infections may indicate that a woman's immune system is not particularly effective in clearing viruses.

This new research is the first prospective study using multiple measurements longitudinally to investigate the relationship between multiple HPV types and a woman's risk for developing pre-cancerous abnormalities in her cervix. During each of the 16,000 patient visits, both the pap smear and HPV tests were administered. The mean follow-up time of the study participants was over three years.

When Franco, Trottier and their colleagues analyzed the data about all patients (women who did not develop pre-cancerous cervical lesions as well as those who did), five HPV types emerged as the most common: 16, 53, 51, 31 and 18. HPV 16's high prevalence in infections was underscored by the scientists' analysis of the HPV types that were identified in all of the infections. HPV 16 was found in 9 to 14 percent of single and multiple infections respectively.

Just over 12 percent of the women tested during the first year were infected with multiple HPV types. Over four years, the total increased to more than 22 percent.None of the HPV types were more involved than other types in co-infections. In future studies, the scientists hope to pinpoint the particular combinations of HPV types that characterize the high-risk co-infections.