Primary Care Corner with Geoffrey Modest MD: Cervical Screening Guidelines From ASCO

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By Dr. Geoffrey Modest

The American Society of Clinical Oncology just published guidelines for the secondary prevention of cervical cancer (see doi: 10.1200/JGO.2016.006577, or go to  http://ascopubs.org/doi/abs/10.1200/JGO.2016.006577 ). These guidelines were unusual in that they stratified the screening approach based on the country’s resources, reflecting a global initiative, and also had several differences from the current US guidelines.

Details:

  • HPV testing is recommended in all resource settings, though visual inspection with acetic acid may be used in countries with basic resources.
  • Frequency of testing:
    • For countries with maximal resources: should be from age 25 to 65, every five years if negative.
    • For countries with enhanced resources: age 30 to 65. If two consecutive negative tests at five-year intervals, then every 10 years. Stop at age 65 if consistently negative results for the past 15 years
    • For countries with limited resources: age 30 to 49 every 10 years
    • For countries with basic resources: age 30 to 49, 1 to 3 times per lifetime
  • Treatment options for patients with a positive screen:
    • In countries with more than basic resources: colposcopy, then loop electrosurgical excision (LEEP) if positive
    • For countries with basic resources: treat with cryotherapy or loop electrosurgical excision
  • Follow-up post-treatment:
    • 12 month follow-up is recommended in all settings
  • For HIV-positive women (also applies to women who are immunosuppressed for any reason):
    • Overall, screen with HPV testing twice as many times per lifetime as in the general population (as above). Screening should begin as soon as they get the HIV diagnosis [? when to start if they are born with the infection/or get it from a transfusion at age 8???].
      • In countries with maximal  resources: screen with HPV every 2-3 years
      • In countries with enhanced resources: screen with HPV at 2-3 year intervals; but if negative, every 5 years (approx 8 screenings in lifetime)
      • In countries with limited resources: twice as often as in general population (4-6 screenings per lifetime)
      • In countries with basic resources: begin screening with HPV if available, or with visual inspection with acetic acid, at age 25, then every 3 years if negative initially. [A bit unclear, since they then suggest it will be approximately twice per lifetime]. These recommendations are based on murky data…
    • Postpartum screening: overall no screening recommended during the pregnancy, partly because the normal immune changes in pregnancy can have increased HPV changes which subside after pregnancy.
      • Screen at six months in all countries other than those with only basic resources, where screen at 6 weeks since longer interval could lead to loss of follow-up [though this might apply to other countries, or areas in other countries as well…..]
    • No screening should be done in people who had a total hysterectomy for benign causes [though see blog https://stg-blogs.bmj.com/bmjebmspotlight/2016/07/18/primary-care-corner-with-geoffrey-modest-md-pap-smears-post-hysterectomy-in-hiv-positive-women/, which would support general screenings in HIV-positive women who had hysterectomy]
    • And, in countries with basic resources without mass screening — infrastructure for HPV testing, diagnosis and treatment should be developed
    • Self-screening: there is evidence that women doing their own HPV sampling may improve screening coverage, though the pooled sensitivity and specificity are lower, especially for CIN2+. So, overall not suggested except in women who might otherwise not get tested at all [and the sensitivity and specificity are actually only a little lower].
    • Postulated effect of HPV vaccine: likely to decrease the incidence of HPV 16/18 cancers, and with approx 5 year later onset of disease as a result of decreasing these most-carcinogenic genotypes, so potentially can start screening later in life, and decrease screening to ages 30, 45, 60. Maybe no need to screen at all??? Or only once??  But all recommendations are pending actual data….

Commentary:

  • High-quality screening programs can lower the incidence of cervical cancer by up to 80%
  • HPV is the most frequent sexually-transmitted infection, with one study finding 43% of college women getting infected over 36 months (see Ho GYF. New Engl J Med 1998; 338:423)
  • As a point of reference, the US screening guidelines at this point are quite different from the above ASCO ones for countries with maximal resources (e.g. the USPSTF recommendations):
    • Begin at age 21, do cytology screening only until age 30, and then every 3 years if normal. HPV testing not recommended because of higher likelihood of unnecessary follow-up and procedures (HPV infection tends to be transient)
    • After age 30, either continue cytology only every 3 years, or do cytology/HPV co-testing every 5 years, if normal results
    • Stop at age 65 unless there is increased risk (history of abnormal screens, prior HPV-related disease, immunocompromise, DES exposure); and if there are 2 negative consecutive co-tests or 3 negative cytologies within prior 10 years; and no history of high-grade dysplasia or worse
  • Although ASCO cites the importance of HPV testing, they do not make formal recommendations about primary HPV testing vs co-testing, noting just that some countries and regions have moved towards adopting primary HPV testing (see https://stg-blogs.bmj.com/bmjebmspotlight/2016/10/12/primary-care-corner-with-geoffrey-modest-md-cervical-cancer-screening-less-frequently/ )
  • The American College of Obstetricians and Gynecologists also just came out with their recommendations in 2016 (though, not sure what to make of this: but these guidelines were retracted from the January 2016 issue of their publication Obstetrics and Gynecology, and I could find only recommendations for HIV-positive women, though these were also retracted), with a few differences from ASCO. for HIV infected women:
    • Start screening within one year of onset of sexual activity, but no later than age 21
    • Screening should be continued throughout a woman’s lifetime and not stop at age 65
    • For women less than 30 years old:
      • Cytology screening (without HPV testing) should be repeated in 12 months (though some people feel it should be followed in six months)
      • If three consecutive cervical cytology tests and normal, follow-up cervical cytology should be done every three years
      • If ASCUS on cytology, and reflex HPV testing is positive, then colposcopy. If HPV testing results are not available, repeat cytology in 6 to 12 months if more advanced dysplasia is found, refer for colposcopy
    • For women older than 30 years old, do cervical cytology or co-testing:
      • If only cytology is done, follow-up is as for women less than 30 years old
      • If co-testing is done and negative, repeat at three years; if cytology is negative and HPV positive, repeat in one year (though if HPV 16/18 is present go directly to colposcopy). if either of the co-tests at one year is abnormal, colposcopy
    • The hope is that as HPV vaccination becomes more widespread, the incidence of cervical cancer will decrease significantly as well as the need to screen for it; though this is in the relatively distant future, given the high prevalence of HPV infections currently, and the vaccine does not help those currently infected or with abnormal cytology from infection
    • They do recommend starting screening at age 25, as is done in several countries in Europe for example, noting that there is lack of evidence of the benefit of decreased cancer risk in those under 25 (very uncommon), and potential harm or screening and overtreatment. The United States still recommends initiation of screening at age 21. And though HPV infections are remarkably common in women under 25 (as noted in study above), HPV infections clear spontaneously, and 90 to 95% of those with even LGSIL as well as many with high-grade lesions regress spontaneously
    • And they recommend HPV screening at age 25 in countries with maximal resources, different from the general recommendations in the US to start HPV screening at age 30
    • So, my guess is that the formal US recommendations will change significantly in their next iteration (the USPSTF recommendations date from 2012, with an anticipated update 2018). Perhaps internal controversy led to ACOG retracting their guidelines??  But it is pretty clear that recently the approach to cervical cancer screening has changed significantly in other countries.
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