Less Cervical Cancer Screening in HPV-Vaccinated Population?

Kristin Jenkins

October 24, 2016

In women who were vaccinated for the human papillomavirus (HPV) at the age of 12 years, cervical cancer screening can start at a later age, take place less frequently, and involve primary HPV testing instead of cytology, suggests analysis of results from a study based on a mathematical microsimulation model.

The model suggests that for women who received the first-generation vaccines active against HPV16 and HPV18, screening could begin at 25 to 30 years of age and be carried out every 5 years. For women who received the more recent HPV-9 vaccine, screening every 10 years would be sufficient.

At present, US guidelines for cervical cancer screening do not differentiate between women who have been vaccinated for HPV and those who have not, the researchers point out.

Jane J. Kim, PhD, of Harvard T. H. Chan School of Public Health in Boston, Massachusetts, and colleagues say that "this analysis supports a reassessment of cervical cancer screening policies in women who have been vaccinated against HPV."

This analysis supports a reassessment of cervical cancer screening policies in women who have been vaccinated against HPV. Dr Jane Kim and colleagues

Making modifications to current guidelines would provide optimal screening that is more cost-effective and more efficient and would reduce risks associated with excessive screening and treatment of precancerous lesions, they add.

Their report was published online October 18 in the Journal of the National Cancer Institute.

At present, US guidelines for cervical cancer screening do not differentiate between women who have been vaccinated for HPV and those who have not, the researchers point out. They recommend that screening policies be evaluated with respect to women who have been vaccinated for HPV and, if necessary, changed.

However, in an accompanying editorial, an expert cautions that optimal cervical cancer screening in HPV-vaccinated women who already have an 85% reduction in lifetime cancer risk "remains unresolved."

Editorialist Philip E. Castle, PhD, MPH, of the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in New York City, agrees that "less is more" when it comes to cervical cancer screening for women who received the HPV vaccine before becoming sexually active. These women "have a lifetime risk of cervical cancer before screening [that] is less than or equal to risk for previous cohorts of women who have undergone a lifetime of high-quality screening," he points out.

However, he also warns that the option to screen less intensively at a later age with HPV testing instead of cytology may not be an option for all HPV-vaccinated women. There is a greater chance that women who received "catch-up vaccination" after the age of 12 became sexually active prior to vaccination, thereby increasing their risk for infection by vaccine HPV types, he explains.

"Current prophylactic HPV vaccines do not treat preexisting infections and related conditions, and therefore the population cancer risk reduction from HPV vaccines is lower in older populations," he writes.

A risk-based approach to clinical decision-making should be extended to cohorts vaccinated after the age of 12, he advises.

"Lower and upper risk thresholds, defining a risk band, should be established to decide at what age screening starts, at what frequency, and when it stops, as well as who would benefit from colposcopy with biopsy and even treatment without a confirmatory biopsy, should the risk be sufficiently high."

"Importantly," he adds, "these risk-based recommendations for clinical actions must to be conveyed to the busy clinician in a simple, clear, and direct manner."

Microsimulation Model of Different Screening Strategies

In the study, researchers used an individual-based microsimulation model of HPV and cervical cancer to project the health benefits, costs, and harms associated with different screening strategies. They looked at women vaccinated with the bivalent vaccine (HPV-2) or the quadrivalent vaccine (HPV-4) or the nonavalent vaccine (HPV-9).

Strategies varied according to whether primary screening involved cytology or HPV testing or a combination of both. Strategies also varied with respect to the age at which screening started, the interval between routine screens, and whether screening tests changed.

Cost-effectiveness was analyzed using thresholds of $50,000 to $200,000 per quality-adjusted life years (QALY) gained.

The study showed that for women who received the bivalent or quadrivalent HPV vaccines, the most cost-effective strategy was either cytology or HPV testing alone, beginning at age 25 or 30 years and repeated every 5 years

For women who received the first-generation vaccines, the cost-effectivesness of such screening ranged from $34,680 to $138,560 per QALY gained. First-generation vaccines protect against HPV16 and HPV18, which together are responsible for about 70% of cervical cancer.

It was not cost-effective to start screening earlier or to perform it more frequently, the investigators write. In women vaccinated with the later nonavalent vaccine HPV-9 — which also protects against five additional carcinogenic HPV genotypes — HPV testing alone every 10 years was efficient, the study showed. Such testing could begin at age 35 years, at a cost of $40,210 per QALY, or at age 30 years, at a cost of $127,010 per QALY.

The mean reduction in lifetime risk for cervical cancer in women vaccinated with HPV-9 was 85.3% in comparison with no intervention, the study showed. With the addition of screening, reductions in lifetime cancer risk ranged from 91% to 99%.

"Given the lower baseline disease risk in women vaccinated with HPV-9, the optimal screening strategies involved later start ages and lower frequencies than for women vaccinated with HPV-2 or HPV-4," the researchers say. "Furthermore, only strategies that involved primary HPV testing were efficient."

The screening strategies in HPV-vaccinated women led to nearly equivalent health benefits in terms of QALYs and reductions in lifetime cancer risk as the screening intensity increased, especially for women vaccinated with the nonavalent vaccine, the researchers note. "The 10-year screening interval in women vaccinated with HPV-9 remained most efficient throughout," they say.

A 10-year screening interval for cervical cancer was also proposed recently by Dutch researchers, as reported by Medscape Medical News.

Funding for the study was provided by the National Cancer Institute of the National Institutes of Health. The study authors and Dr Castle have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online October 18, 2016. Abstract, Editorial


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