HPV - Huge Paradigm Variation

I'm not sure if that title makes sense. Regardless, this is a wonderfully important study, that even though the big blogs will assuredly address it, I need to try and publicize it as much as possible. Published in New England (online only, text version not until the end of the month), these Indian researchers have shifted how we will screen for one of the most deadly diseases on the planet. The evidence against the Pap smear has been mounting for some time, with convention being the only residual argument for it in our changing molecular environment, with effective vaccines and with molecular testing. A developed world study, also published in New England (from my two alma matars), argued that HPV testing has better sensitivity for detecting cervical cancer. Now, in a developing region, we have evidence not just for the arguably-useful outcome of cervical cancer detection, but mortality itself, with HPV testing saving significant numbers of lives compared with traditional methods of cervical cancer screening. Crucially, the patients testing negative for HPV had no deaths in the eight years they were followed, ie the false negative rate was appropriately low.

I'll leave aside the methodology - it appears sound from my assessment. They have powerfully shown that screening women greater than 30, ie at least 15 or 20 years from their first sexual exposure, with HPV testing leads to an appropriate detection rate of cervical cancer. These cases can then be treated, with proven survival benefits, skipping the notoriously subjective Pap smears and visual inspection (especially in cost-limited healthcare settings with large quality variability). The treatment algorithms haven't been fully codified yet - but hopefully this will be worked upon.

They have demonstrated that HPV testing is both reproducible and objective, and something that can be easily scaled up in the developing world. The next steps are to bring down the costs of the tests themselves, something that will hopefully happen as demand goes up and competition arises, as well as governments throwing in their funding dollar in what is clearly an important area of investment. Also, figuring out just how often to screen women is still to be determined - a ten year window may be reasonable, though long-term studies will need to be done to determine that. In addition, making sure that any tests include all of the HPV serotypes, not just the ones covered by the new vaccines, is crucial, as widespread vaccination may lead to serotype switching. What level of screening an HPV-negative women deserves still is under debate, however. Also, screening of young women, ie less than 15 years after their first sexual exposure, with their extremely low incidence of cervical cancer may be antiquated.

The accompanying editorial makes the good point that this may be slow to disseminate in places like the USA, where Pap smears form the basis of primary care for women in this age group, and that cytology could be used as a secondary screen for HPV positive women. Regardless, this is a huge leap forward for cervical cancer screening for the entire planet, and may be one more step towards making the routine Pap smear a thing of the past.