Author: Laurie Barclay, MD

High coverage of quadrivalent human papillomavirus (HPV) vaccination in young Australian women resulted in a lower frequency of genital warts, which might protect heterosexual men through herd immunity, according to the results of an analysis of national sentinel surveillance data published online November 9 in Lancet Infectious Diseases.

“The natural history of cervical and HPV-associated diseases is slow,” Mark H. Einstein, MD, MS, associate professor of obstetrics and gynecology and women’s health, and director of clinical research for women’s health and gynecologic oncology at Albert Einstein College of Medicine and Albert Einstein Cancer Center, Montefiore Medical Center, in New York City, told Medscape Medical News when asked for independent comment. “This is the first registry-based study that has already shown the declines after vaccinating a large population of vaccine-eligible adolescents and young adults. This prospectively shows what all the models have been predicting all along.”

The annual incidence of genital warts has been increasing for decades and is currently about 1% in young, sexually active people. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, which are 2 of the 4 types targeted by the quadrivalent HPV vaccine used in Australia (Gardasil; CSL Biotherapies).

“While it will probably be as effective as the quadrivalent HPV vaccine at preventing anogenital and other cancers, the bivalent HPV vaccine (Cervarix, GSK) used in the UK national program provides no protection against genital warts,” lead author Basil Donovan, MD, head of the Sexual Health Program, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, in Sydney, Australia, said in a news release.

Beginning in July 2007, Australia was the first country to fund an HPV vaccination program for all women 12 to 26 years of age. Using a national surveillance network, the investigators assessed trends in diagnoses of genital warts in Australia from January 2004 to December 2009. New patients attending 8 sexual health services in Australia during that time provided standardized data for demographic factors, frequency of genital warts, HPV vaccination status, and sexual behavior.

Significant trends in proportions of patients diagnosed with warts in periods before and after vaccination began were identified using χ2 analysis. The main study population was female Australian residents eligible for free vaccination, but the investigators also analyzed data for patients ineligible for free vaccination, including women older than 26 years of age, nonresident women, and men.

Genital warts were identified in 9867 (9%) of 112,083 new patients attending sexual health services between 2004 and 2009. Before the vaccination program began, the proportion of women or heterosexual men diagnosed with genital warts did not change, but after vaccination began, young female residents had a significant decline in number of diagnoses of genital warts from 11.7% in July to December 2007 to 4.8% in July to December 2009 (59% change; P trend < .0001). There was no significant decrease in diagnoses of genital warts among female nonresidents, women older than 26 years in July 2007, or men who have sex with men. During the vaccine period, proportionally fewer heterosexual men were diagnosed with genital warts, from 12.3% to 8.9% (28%; P trend < .0001). This effect was most apparent in young men. By 2009, 65.1% of female Australian residents who were eligible for free vaccine had received quadrivalent or unknown HPV vaccine. "The strengths of this study are the large numbers and the very high uptake in Australia, which came about for a number of reasons," Dr. Einstein said. "Firstly, the year the quadrivalent vaccine was introduced, one of the patent holders of the technology, Ian Frazer, was named Australia's Man of the Year. Also, the prime minister's wife came out saying she was a cervical cancer survivor, and all this led to large campaigns for young women being vaccinated." Limitations of this study include the failure to yield true population-based data on genital warts; the use of a clinic-based sample, with possible bias against detecting a decline in incidence of genital warts; and misclassification of some women as eligible or ineligible for free vaccination. "The decrease in frequency of genital warts in young Australian women resulting from the high coverage of HPV vaccination might provide protective effects in heterosexual men through herd immunity," the study authors write. "The high morbidity in [men who have sex with men] attributable to HPV-related disease, including anal cancer, and the possible role of anal warts in facilitation of transmission of HIV, means that this group should be considered in future HPV-vaccination programmes." When asked about suggestions for additional research, Dr. Einstein recommended continued follow-up with good registries in well-vaccinated populations, such as many Western European countries (including the United Kingdom, Scandinavia, Belgium, Netherlands, Australia) and certain provinces in Canada, where most young adults have already been vaccinated. If possible, he also suggested linking the disease with HPV types in some subsets of these populations. "We hope that our findings of national population benefit from the quadrivalent HPV vaccine, showing much the same efficacy as in clinical trials, will be followed by widespread reductions in infection and disease from oncogenic HPV 16 and 18," the study authors conclude. "This reduction might already be underway, but will take longer to document than did decreased incidence of genital warts." CSL Biotherapies supported this study. Some of the study authors report various conflicts of interest with CSL Biotherapies, Sanofi Pasteur, GlaxoSmithKline (GSK), and/or Merck. Dr. Einstein has advised or participated in educational speaking activities but does not receive an honorarium from any companies. In specific cases, his hospital, Montefiore Medical Center, has received payment for his time spent for these activities from Merck and GSK. Montefiore has also received grant funding from Merck and GSK for research related costs of clinical trials for which he has been the Montefiore PI. Source: Lancet Infect Dis. Published online November 9, 2010.