Primary Care Corner by Geoffrey Modest MD: pap in women with HPV vaccine jnci2016

By Dr. Geoffrey Modest

Given the recent 2 articles on cervical cancer screening (https://stg-blogs.bmj.com/bmjebmspotlight/2016/10/12/primary-care-corner-with-geoffrey-modest-md-cervical-cancer-screening-less-frequently/ and https://stg-blogs.bmj.com/bmjebmspotlight/2016/10/17/primary-care-corner-with-geoffrey-modest-md-cervical-screening-guidelines-from-asco/), I thought I would add (briefly) a third to the troika (see doi: 10.1093/jnci/djw216). Funded by National Cancer Institute of the NIH and done by Harvard School of Public Health.

Details:

  • This is a mathematical modeling of the cost-effectiveness of different cervical cancer screening approaches in HPV-vaccinated women
  • They looked at different levels of cost-effectiveness thresholds: from $50K to $200K per quality-adjusted life-year (QALY) gained

Results:

  • In women who were fully vaccinated with either the bivalent or quadrivalent HPV vaccine, optimal screening strategies involved either cytology or HPV screening alone every 5 years starting at age 25 or 30 (cost-effectiveness ratios ranging from $34,680 to $138,560 per QALY gained
  • In women vaccinated with the nonavalent vaccine (that being: 9 HPV genotypes), only HPV testing by itself was efficient, with both decreased frequency (every 10 years) and starting later at age 35 ($40,210 per QALY) or age 30 ($127,010 per QALY)
  • If there were in reality decreased nonavalent vaccine efficacy, then the 10-year HPV screening should start at age 25 or 30.

Commentary:

  • This article does highlight the issue mentioned briefly in the prior 2 blogs: HPV vaccination might significantly change the cervical cancer screening algorithm
  • The nonavalent vaccine, the one we use now, covers 90% of the carcinogenic HPV types (including the biggies 16/18), as well as 2 of them (6/11) associated with noncarcinogenic genital warts
  • But, there are certainly concerns about directly applying the above:
    • The US rates of HPV vaccination remain <50%
    • There are very limited real-world data on the effectiveness of the vaccines in reducing HPV infection and, especially, the development of precancerous or cancerous lesions
    • This relies on mathematical modeling, which without any real data, is likely fraught with potential errors in assumptions
    • There is potential collateral benefit from screening less: fewer harms from unnecessary colposcopies (???though are we missing some of the “necessary” ones??)
  • So, this adds some to the argument that we need to screen less. The analysis/conclusions would be different if women did not receive the vaccine before they had sexual relations (though, important to remember that HPV can be transmitted without penetrative sexual relations), or did not receive the full series of shots. And the real issue is waiting for real data about the effects of vaccinations in the real world on the incidence of actual CIN and advanced cervical cancer and morbidity/mortality. I am also a little leery about the effect of doing many fewer pelvic exams: I find now that some newer clinicians are less confident doing them, and sometimes do not do them when there are clear clinical indications. This potential adverse effect should somehow be factored into the risk/benefit analysis…
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