How HPV vaccine will—and won’t—change practice
Franco EL, Harper DM. Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control. Vaccine. 2005;23:2388–2394.
Cervical screening will continue, but will be more accurate and more efficient.
Yes, we are on the verge of the possibility of reducing the risk of cervical cancer to close to zero, but it will take decades. Vaccinating young girls will not significantly reduce cervical cancer rates until these girls reach the median ages of microinvasive (early 40s) and invasive (late 40s) cervical cancer.
Even then, cervical cancer rates will depend on these factors:
- the extent of vaccination coverage
- the number of high-risk HPV types in the vaccine
- whether vaccination provides multidecade protection or falls off with time
- whether the medical community and the public continue to diligently follow recommended screening guidelines
If immune protection falls with time, booster HPV vaccine shots should provide ongoing protection, but population protection will depend on the percent of the population obtaining the booster. If the population becomes complacent about cervical screening as risk for cervical cancer decreases, then cancers will develop that would have otherwise been prevented.
Why screening will continue
Virus-like particle (VLP) vaccines for all of the important oncogenic HPV types could, theoretically, be produced. But until long after multivalent HPV vaccines that include all the important oncogenic types are available, women will require screening to prevent the 30% of cancers that occur from other high-risk HPV types not in the present vaccine. And, we will need screening to protect women who are not vaccinated, and those already infected.
As Franco and Harper stressed, “Although the future seems bright on the vaccine front, policy makers are strongly cautioned to avoid scaling back cervical cancer screening. Any premature relaxation of cervical cancer control measures already in place will bring a resurgence of the disease to the unacceptable levels of the not too distant past.”
In other words, cervical screening will continue for the foreseeable future.
A peek at a “new world”
Fewer abnormal Pap tests. The vaccine will likely steadily decrease the rate of abnormal Paps that are important, as an increasing proportion of women are vaccinated against the 2 most common types in high-grade CIN.
Colposcopies and cervical treatments will decline in number coincident with the proportion of the population vaccinated.
A training challenge? This change will decrease the number of significant lesions that a colposcopist may see, increasing the challenge of training and maintaining expertise in identification and treatment of these lesions. As significant Pap abnormalities decrease, maintaining expertise in cytologic interpretation, and even in maintaining attention to detail, may become more difficult.
Specific testing. Finding women with significant abnormalities may more and more be accomplished with the accuracy afforded by testing for specific HPV types known to be most at-risk for CIN 3+.
With respect to cervical cancer prevention, the years to come will surely be a new world, different from what we all have known.
Improving folate status protects against HPV
Piyathilake CJ, Henao OL, Macaluso M, et al. Folate is associated with the natural history of high-risk human papillomaviruses. Cancer Res. 2004;64:8788–8793.
Improving folate status in women at risk of getting infected or already infected with high-risk HPV may help prevent cervical cancer. It is reasonable to advise women with HPV that folate supplements may be helpful.
Recommending oral folate supplements is one of the few things we can offer that can empower our patients with something positive that they can do for themselves.
A subset of women in the ASCUS LSIL Triage (ALT) study were evaluated prospectively to determine whether systemic levels of folic acid are associated with the occurrence and duration of HPV infections after controlling for other micronutrients (vitamins B12, A, E, C, and total carotene) and for known risk factors for high-risk HPV infections and cervical cancer. Hybrid Capture 2 and serum levels of these micronutrients were obtained at 6-month intervals throughout the trial’s 2-year follow-up.
Women with higher folate status were significantly less likely to be repeatedly HPV positive, more likely to become testnegative during the 2-year study, and 73% less likely to become newly HPV positive.
These associations held after controlling for other micronutrients and known risk factors for HPV. The authors reviewed a possible role of folate in preventing integration of HPV, thereby improving clearance of HPV infections, and documented that increased folate levels were also protective against the development of CIN 2/3.
Food fortification with folate became mandatory in the United States in 1998. The median folate level in women in this study mirrored the median post-fortification level for women in the United States—indicating that folate levels in food are not adequate to affect HPV status.
Therefore, it appears reasonable to advise women with HPV that taking folic acid supplementation in the levels usually advised for pregnant women may be helpful.