USPSTF guidelines on cervical cancer screening, and recs for HIV pts

The USPSTF just released their new cervical cancer screening guidelines (see https://jamanetwork.com/journals/jama/fullarticle/2697704?resultClick=1 for the recommendations, and https://jamanetwork.com/journals/jama/fullarticle/2697703 for the evidence report and systematic review).

Details/Results:

-- 8 RCTs (n=410,556), 5 cohort studies (n=402,615), and 1 individual participant data meta-analysis (n=176,464) were included

-- primary high risk human papillomavirus (hrHPV) testing (ie, the sole test performed) vs cytology:

    --increased detection of CIN 3+ on the first round of testing, ranging from RR of 1.61-7.46

    --in general the detection rate was significantly lower in the second round of screening

-- co-testing (both cytology plus hrHPV) vs cytology alone:

    -- none of the studies showed improvement in CIN 3+ by co-testing

-- false positives were:

    --cytology: 2.6-10.9%

    --primary hrHPV:  6.6-7.4%; culposcopy rates: 1.2-7.9% vs 1.1-3.1% for cytology

    --cotesting: 5.8-19.9%; culposcopy rates: 6.8-10.9% vs 3.3-5.2% for cytology

Recommendations:

-- women 30 to 65 years old can choose a variety of cervical cancer screening options:

    -- primary high risk human papillomavirus (hrHPV) testing (ie, the sole test performed) every 5 years, a preferred strategy (Grade A recommendation)

    -- cervical cytology every 3 years, a preferred strategy (Grade A recommendation)

    -- co-testing every 5 years of both cytology and hrHPV, an alternative strategy because of increased testing/procedures (and also has the highest false positive rate)

-- women 21 to 29 would still get cytology every 3 years

-- testing is not recommended for (all with Grade D recommendations):

    -- women younger than 21

    -- women over 65 who aren’t at high risk and have had adequate prior screening

    -- women who have had a hysterectomy with cervix removal who did not have prior high-grade precancerous lesions

Commentary:

-- cervical cancer deaths in the US has decreased worldwide since the implementation of cervical cancer screening programs. For example, even a single screening test by hrHPV in India found a 50% reduction in cervical cancer (this finding on single screening is reinforced by the above-noted significantly lower CIN 3+ in the second round of screening)

-- in the US, the death rate has further decreased from 2000 (2.8 deaths/100K women) to 2015 (2.3 deaths/100K women). But in 2018, the estimates are that there will still be 13,240 new cases and 4170 deaths from cervical cancer

-- in 2013 in the US, 82% of women aged 21-44, and 79% aged 45-64 reported a Pap smear in the past 3 years

-- mean age of cervical cancer diagnosis is 49 years

-- racial/ethnic/geographic/financial differences:

    -- African-American women have a death rate for cervical cancer at 10.1 deaths/100K women, which is more than twice the rate of white women; mortality is also higher among older African-American women. Though it seems that the screening rates for African-American women are similar to white women, the higher mortality rate may be attributable to differences in follow-up and treatment afterwards. Also, for unclear reasons, African American women with cervical cancer seem to have a higher than average rate of adenocarcinoma, with its attendant worse prognosis.

    -- American Indian/Alaska native women also have higher rates of cervical cancer mortality, at 3.2 deaths/100K women; these women have a lower screening rate and inadequate follow-up

    -- Hispanic women have a slightly higher incidence rate of cervical cancer and slightly higher mortality (2.6 deaths/100K women), with especially high rates along the Texas-Mexico border

    -- white women living in Appalachia and other geographically and medically isolated areas have much higher mortality rates than the US average

    -- 23.1% of women without health insurance, and 25.5% of women with no regular healthcare clinician have not had a Pap in the last 5 years, vs 11.4% of the general population (ie, twice as many!! oh, it would be great to have an inclusive and accessible health care system.....)

-- a few other comments: cytology screening does rely on cytopathologists, and there is significant inter-observer variability (though there are now approved automated slide interpretation devices).  HPV specimens can be self-collected by women, and small studies have shown satisfactory results (but probably not quite ready for prime-time as a routine, though might be useful for women declining a speculum exam or in resource-poor areas, with the further caveat that the ideal method of getting the specimen is still not clear). perhaps notably, the WHO does not even mention the co-testing strategy (see http://apps.who.int/iris/bitstream/handle/10665/94830/9789241548694_eng.pdf;jsessionid=BEE2B9852ED2EE947B96BEDA9CB11CD4?sequence=1​ )

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For HIV positive women, the US guidelines from May 2018 (see https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-oi-prevention-and-treatment-guidelines/343/hpv ) are:

--women 21-29: pap test at initial diagnosis, then at 6-12 months later, and every 3 years after 3 consecutive negative paps

--women 30 and older: as with women 21-29 if do just cervical sampling. Can do co-testing every 3 years if negative cytology and HPV. evaluations should continue throughout a woman’s lifetime and not stop at age 65. HPV vaccines should be given, and the younger the better (better to vaccinate prior to people getting HPV infection), and both males and females should get the vaccine ages 9-26, though efficacy data are lacking (there are data showing immunogenicity of the vaccine, as well as later anamnestic responses)

--no comment on primary HPV testing, but these guidelines predate the new USPSTF ones. some data do suggest benefit for primary HPV testing, in women younger than age 50 (see https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.21955​ )

 --see the guidelines for more information on what to do if these exams are not negative

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so,

it does seem that primary hrHPV screening is the way to go for those women 30 and older (and this does seem to be the way several other countries are going). co-testing does not seem to add much other than cost and false-positives (which also lead to more testing, and cost). and, it is important, i think, to reinforce prevention of HPV infections (ie, immunizing kids, beginning at age 9 when there are only 2 shots needed and the shots are more immunogenic at an earlier age), though this was not part of these USPSTF recommendations. but, the anticipation of these new USPSTF recommendations is that these are likely to be the accepted approach in the future, and the one that insurers are required to cover.

see http://gmodestmedblogs.blogspot.com/2015/01/primary-hpv-testing-for-cervical-cancer.html  for an array of former blogs on primary HPV testing trials and former recommendations

also, see http://gmodestmedblogs.blogspot.com/2017/10/primary-cervical-hpv-screening-and.html for a blog on primary cervical HPV screening in an Australian cohort, finding that there was an increased detection rate for high-grade pre-cancerous lesions, and subsequent decreases in CIN3 and invasive cervical cancer vs cytology screening, as well as another article noting that using HPV vaccines was associated with almost no subsequent high-grade cervical, vulvar and vaginal lesions from the major oncogenic HPV strains

and, http://gmodestmedblogs.blogspot.com/2018/02/new-adult-and-pedi-immunization.html which has a few studies suggesting that younger kids (9-14) do well with just 2 HPV shots, and that in older kids getting a 3^rd dose of HPV vaccine, it may be better to delay the third dose to to >8 months after the second one

geoff​

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