home HPV testing in women

 

A recent article assessed the public health and economic outcomes in women doing HPV self-sampling for cervical cancer screening (see hpv self-testing jama2023 in dropbox, or doi:10.1001/jamanetworkopen.2023.4052).

 

Details:

-- 19,581 women were selected, aged 30-64 in the Kaiser Permanente Washington health plan, randomized to usual care (patient reminders and ad hoc outreach) vs that plus mailed HPV sampling kits

    -- all women were at least 3 years 5 months from last pap test, had not had hysterectomy, and had no high-risk HPV test within the past 3 years 5 months

-- mean age 50, 77% white/5% Black/10% Asian, BMI 52% 18.5-30/18% 30-35/13% 35-40/15% >40; smoking never 61%/current 15%/former 24%, Charlson comobrbidity index 0 in 815/1 in 11% (ie not many medical comorbidities)

-- time since last pap, stratified by time enrolled in health plan:

    -- in plan 3.4 to 5 yrs:  no pap test done in 68%, 32% had pap within 3.5-5 yrs

    -- in plan 5-10 yrs: no pap done in 34%, 49% had pap done in 3.5-5 yrs, 17% had pap done 5-10 yrs

    -- in plan >10yrs: no pap done in 15%, 49% had pap done in 3.5-5 yrs, 25%  had pap done in 5-10 yrs, 11% had pap done in >10yrs

-- the HPV kits were mailed to recipients with a letter clarifying that this was a voluntary study, advising they also get their regular pap tests. if the HPV kit was not returned within 3 weeks, there were up to 3 reminder calls

-- primary  outcomes: 

    -- histologically diagnosed CIN2+ and treated CIN2+ (assessed within 6 months of abnormal screening)

    -- primary economic outcome: incremental cost-effectiveness ratio (ICER) for increased screening uptake (ie incremental difference in cost between the 2 groups divided by the difference in the number of women completing screening). this study predated the current guidelines recommending primary HPV screening. The financial assessment included all labor and nonlabor costs

-- followup was up to 18 months after randomization

Results:

-- screening uptake: intervention group 26.3%, control group 17.4%

    -- 51% more screening done in intervention group, HR 1.51 (1.43-1.60)

-- positive CIN2+ results: intervention group 12 patients, control group 7 patients

    -- not statistically significant 70% increase, HR 1.70 (0.67-4.32), but very low numbers of patients

 

-- economic results:

    -- the screening uptake, comparing those in the intervention vs control groups:

        -- age 30-39:

            -- no prior test done: 17.8% vs 9.4%

            -- between 3.5-5 years since last test: 34.9% vs 29.1%

            -- between 5-10 years since last test: 24.5% vs 14.1%

            -- > 10 years: 13.3% vs 7.1%

        -- age 40-49:

            -- no prior test done: 13.2% vs 8.7%

            -- between 3.5-5 years since last test: 38.5% vs 27.2%

            -- between 5-10 years since last test: 20.6% vs 15.3%

            -- > 10 years: 10.4% vs 5.6%

        -- age 50-64:

            -- no prior test done: 14.2% vs 5.3%

            -- between 3.5-5 years since last test: 38.2% vs 28.5%

            -- between 5-10 years since last test: 24.1% vs 11.7%

            -- > 10 years: 13.1% vs 4.2%

 

    -- overall ICERs (incremental cost-effectiveness ratios): the total sample range from $85.84 ($85.68-$85.99) per additional completed screening to $146.29 ($146.20-$146.38) by using Medicare-based pap-only visit costs

 

Commentary:

-- Cervical cancer screening has evolved dramatically from yearly Pap smear screening of all women decades ago, to screening women when they reach the age of 21, to screening much less often (to three years and now to five years in women over 30 for women who have both Pap smear cytology as well as HPV testing), to primary HPV testing (eliminating the cytology component), to women self-testing with HPV tests without the need for a clinical exam. The guidelines do vary: USPSTF suggests cytology screening every 3 years til 29yo then either continued cytology every 3 yrs or HPV testing with or without cytology every 5 years (see hpv primary test uspstf jama2018 in dropbox or doi:10.1001/jama.2018.10897); the American Cancer Society suggests starting at age 25 with primary HPV testing every 5 years (as does the UK) and this is consistent with the ACOG guidelines

    -- Primary HPV testing has been used in in Turkey and Italy since 2014: https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(19)30491-4/fulltext 

 

-- this study had several findings:

    -- the screening uptake (ie, the % of women who actually had screening) increased pretty dramatically in all groups of women mailed the HPV self-testing kits (though there was pretty aggressive follow-up to help ensure better adherence to this)

        -- and this seemed to be especially significant in women who either had no prior test documented or a long time since prior evaluation

    -- there were very few women with more advanced cervical lesions, so not able to generate potentially statistically significant differences

    -- there was cost-effectiveness at lower system willingness-to-pay levels in women aged 50-64 and in those whose last pap test was within 3.5-5 years than in other subgroups

 

-- The issue of women self-testing for HPV is another example of empowering patients as well as decreasing the number of unnecessary and invasive tests. and per the above article, also is "cost-effective".  However, it does raise a concern about the overall direction of primary care:

    -- self-testing will likely mean that many of us in primary care will have less experience doing pelvic exams, and may not feel as comfortable being able to differentiate normal versus abnormal exams and therefore less able to help women with gynecologic problems. This is not so dissimilar from other examples in medicine:

        -- many clinicians do not feel comfortable doing eye exams. To me this is a significant problem, given that patients who come in with headaches should have their optic discs assessed for papilledema

        -- many clinicians also do not seem to be very comfortable with their cardiac exams. Any "abnormality" is referred for an echocardiogram, though a sufficient clinical exam might obviate the need for an echo

        -- many clinicians also are sending many patients to specialists, in part because of the tremendous time constraints and pressures on primary care (see http://gmodestmedblogs.blogspot.com/2023/04/healthcare-worker-burnout-whither.html ), and not necessarily because the patient needs specialty care. This may well lead to a cycle of clinicians not feeling comfortable with treating these conditions or prescribing some of the new drugs (eg, with the new diabetes or heart failure medicines), reinforcing further discomfort with treating these patients. And, this could lead to primary care devolving into more of a triage of patient care to specialists (perhaps unnecessarily), and undercutting (I think) our ability both to provide holistic care to the patients and to get the academic stimulation of understanding/treating the clinical issues

 

-- there was a meta-analysis done several years ago on the efficacy of HPV self-testing using PCR assays, finding that it was as accurate as clinician-based screening and had a much higher response rate than being invited to get tested by a clinician. this was particularly effective when community health workers delivered the test kits to women, less so with just mailing out the kits (see http://gmodestmedblogs.blogspot.com/2018/12/hpv-self-testing-and-hpv-prevalence.html )

 

-- it seems that some insurers in the US cover a small amount of the cost of HPV self-tests, though there still seems to be a pretty hefty out of pocket expense. And so far these tests are not FDA-approved. They are, however, covered as part of the National Health Service in the UK

 

-- and, of course, the good news: the decline in cervical cancer in young women is likely from the effects of vaccination against HPV (eg, see http://gmodestmedblogs.blogspot.com/2019/04/hpv-vaccination-dramatic-decrease-in.html ). and vaccination needs to be a top priority for both women and men (and especially targeting young kids, who have the highest antibody response to the vaccination and the best HPV infection prevention: (see blogs noted below)

 

Limitations:

-- this was a single (but large) insurer in Washington state, so the results may not be generalizable to other areas or to individuals who would not qualify for this type of insurance

-- they excluded women with recent high-risk HPV infections, which limits generalizability to the significant numbers of people who have chronic high-risk HPV infections

-- this study was limited to mailed HPV kits, which might not be as effective as other methods (see above), and that might thereby alter their economic analysis.

-- a systematic change to home-based HPV testing would require systems changes at all levels, and especially at the local clinic level: developing processes to mail lots of kits to lots of women, developing processes to make sure that the HPV testing were done, and having more access to necessary followup for the increased numbers of women who would be found to have high-risk HPV detected (including both clinical and nonclinical personnel, as well as more access to trained culposcopists and necessary equipment, etc)

    -- and this would include women who have non HPV 16 or 18 subtypes, who should get further testing (eg in-clinic cytology).

-- the costs used in their economic analysis were based on those in the particular health care system (Kaiser-Permanente) and are not necessarily similar to the costs in other areas/systems

    -- and all women in this study had insurance and a primary care provider (which happens in 88% and 75%, respectively, in the more general population). so, unable to generalize these results for our overall population (rather unfortunately, with our noninclusive/fragmented health care system....). and people from many settings are in fact minimized in this Kaiser-Permanente group, especially those with lower income/uninsured or living in more rural settings

    -- also, no data on prior HPV vaccine status, which clearly would affect the results; this issue also may well be a more significant problem in a less cohesive setting than Kaiser-Permanente

-- hard to quantify the actual benefit of home-based testing from this study in terms of more advanced cervical pathology (CIN 2+), since very few had that (12 in HPV group vs 7 in controls). likely that a larger sample or higher risk groups might have had statistically significant results. and perhaps longer followup would be necessary to show benefit

-- likely that many women in the "no prior test done" group included women who did have testing done when covered by a prior different insurance (too bad we don't have a national database of all preventive care done ......)

 

so, a few issues here:

-- there clearly is a benefit to having women do HPV self-testing, in terms of ease of performing an important intervention to reduce cervical cancer, a very likely increased adherence rate of testing (as found in this study), an important goal of patient self-care and self-realization, and (rather likely) a decrease in cervical cancer outcomes

-- this intervention is low-cost and pretty easy to implement (given adequate resources, as above)

-- this self-testing should be part of our public health campaign to decrease cervical cancer, hand-in-hand with promoting vigorous HPV vaccinations

-- and, perhaps there should be trials of oral self-testing for HPV, especially in men who have high (and increasing) risk of oral HPV infections and oropharyngeal cancers (see http://gmodestmedblogs.blogspot.com/2017/10/oral-hpv-in-men-and-oropharyngeal-cancer.html )

 

--prior blogs of note, largely on the HPV vaccine (there are lots of them, accessible at http://gmodestmedblogs.blogspot.com/search?q=hpv+vaccine:

    -- children 9-14 have a more profound immunologic response to vaccine and can get just 2 shots:  http://gmodestmedblogs.blogspot.com/2016/11/2-dose-hpv-vaccine-for-girls-and-boys.html 

    -- there may be benefit in those people on the 3-dose regimen in delaying the 3^rd dose until at least 240 days after the second one: http://gmodestmedblogs.blogspot.com/2018/02/new-adult-and-pedi-immunization.html

  -- there is development of herd immunity by vaccination, especially in men: http://gmodestmedblogs.blogspot.com/2019/10/hpv-vaccine-and-herd-immunity-in-men.html

 

geoff

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