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Study IDs Cervical Cancer-Associated HPV Genotypes in New Mexico

NEW YORK (GenomeWeb News) – A large genotyping study in New Mexico has linked the human papillomavirus genotypes HPV16 and HPV18 to most of the invasive cervical cancer cases in that state in the 1980s and 90s.

A team of researchers from the University of New Mexico, the National Cancer Institute, and the DDL Diagnostic Lab in the Netherlands genotyped HPVs isolated from more than 2,000 cancer in situ or precancerous lesions and invasive cervical cancers, collected over 20 years, comparing these with 4,000 healthy control samples. The research, which appears online today in the Journal of the National Cancer Institute, indicates that HPV16 was associated with the majority of cancer in situ and invasive cervical cancer cases.

In addition, the results suggest that HPV genotype influences everything from cancer invasiveness to age at cervical cancer diagnosis. The researchers argue that such efforts should prove useful for gauging the effectiveness of new and existing HPV prevention efforts.

"[The study] provides important baseline data for evaluating the effectiveness of newly implemented HPV-based technologies, HPV vaccines, and HPV screening in the prevention of cervical cancer," lead author Cosette Wheeler, molecular genetics and microbiology researcher at the University of New Mexico Health Sciences Center, and her colleagues wrote.

"Moreover," they added, "these data can guide the future application of these technologies to maximize the cost-effective, public health benefits of these interventions."

New HPV vaccination and testing approaches have been introduced in the past decade or so as part of an ongoing effort to curb HPV infections, the primary known cause of cervical cancer. In 1999, the US Food and Drug Administration approved Digene's HPV Test, which can identify 13 HPV genotypes contributing to cervical cancer risk. (Digene was acquired by Qiagen last year.)

And in 2006, the FDA approved Merck's HPV vaccine Gardasil, which protects against four HPV genotypes: HPV16, HPV18, HPV6 and HPV11. GlaxoSmithKline submitted a Biologics License Application to the FDA in 2007 for its own vaccine, Cervarix, which targets HPV16 and HPV18. That vaccine has already been approved in Europe.

"Population-based studies of HPV genotype prevalence are needed to predict how these two approaches might influence cervical cancer prevention and how prophylactic HPV vaccination of young women could affect the secondary prevention of cervical cancer," the authors noted.

In an effort to determine which HPV genotypes are most often associated with precancerous lesions or invasive cervical cancer in New Mexico, the researchers used PCR-based approaches to genotype 1,213 paraffin-embedded precancerous lesions diagnosed between 1985 and 1999 and 808 invasive cervical cancer cases diagnosed between 1980 and 1999. These cases were identified through the New Mexico Surveillance, Epidemiology, and End Results Registry.

The team compared these with specimens collected during Pap tests from more than 4,000 healthy controls between the ages of 18 and 40 years old between 1996 and 2000. More than a third of the controls contained HPV, most commonly HPV16, HPV53, or HPV54.

Among the invasive cervical cancer samples, more than half — 53.2 percent — contained HPV16. Another 13 percent contained HPV18 and about six percent contained HPV45. Four percent of invasive cases contained HPV31 or HPV33.

In addition, the team found that HPV16 or HPV18 positive invasive cancers tended to be diagnosed roughly five years earlier than cancers associated with the other HPV genotypes.

HPV16 was also associated with more than 56 percent of the precancerous lesion (also known as cancer in situ) cases. But in this group, HPV31 was detected in nearly 13 percent of the precancerous lesion samples and HPV33 was detected in about eight percent. Fewer than six percent of women carried HPV18.

The team reported that 16 percent of the precancerous and invasive cancer cases contained multiple HPV genotypes.

Interestingly, their analysis suggests that the proportion of HPV16-related cancers declined in the most recent years of the study, despite the fact that samples were collected before the HPV vaccine was available in the US. They credit the drop in HPV16-related cancers to increased screening efforts, which may have prevented precancerous lesions from becoming full-blown cancers.

Based on their results, the rarity of cervical cancers in women under 25 years old, an increase in vaccinations that target HPV16 and HPV18, and the observation that current screening approaches usually don't prevent invasive cancers in young women, the authors suggested that it may be worth considering a delay in the initiation of cervical cancer screening programs. In the US, such screening is currently recommended for women 21 years old or older or within three years of first sexual activity.

In an editorial scheduled to appear in the same issue of JNCI, a trio of researchers from the US Centers for Disease Control and Prevention called the team's state-wide study "a potentially useful model" for gauging HPV-related health outcomes.

Even so, senior author Mona Saraiya, of the CDC's National Center for Chronic Disease Prevention and Health Promotion, and her colleagues noted that although there are ongoing efforts to monitor HPV-related outcomes, "challenges remain to link data from immunizations, cervical cancer screening, and outcomes that will allow comprehensive monitoring and evaluation."

The CDC team also discussed a range of HPV-related issues including the debate surrounding the age at which cervical cancer screening should begin and the potential impact of HPV vaccination and testing strategies. "Continued work is needed to determine the best methods for monitoring vaccine impact and optimal strategies for both primary and secondary prevention of cervical cancer," they concluded.