{"id":1163,"date":"2016-10-12T14:41:50","date_gmt":"2016-10-12T14:41:50","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1163"},"modified":"2017-08-21T10:47:08","modified_gmt":"2017-08-21T10:47:08","slug":"primary-care-corner-with-geoffrey-modest-md-cervical-cancer-screening-less-frequently","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/10\/12\/primary-care-corner-with-geoffrey-modest-md-cervical-cancer-screening-less-frequently\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Cervical Cancer Screening Less Frequently?"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>A recent review of cervical\u00a0HPV screenings in the Netherlands found that those with negative screening could potentially be screened less frequently than every 5 years (see\u00a0doi.org\/10.1136\/bmj.i4924).<\/p>\n<p>Details:<\/p>\n<ul>\n<li>43,339 women aged 29-61 with a negative HPV and\/or cytology were randomly assigned to HPV and cytology co-testing (intervention group)\u00a0or cytology testing alone (control group); with 3 screens: at baseline, 5 years and 10 years; and with followup at 14 years. Those in the cytology only group also got HPV testing but this was blinded to all.<\/li>\n<li>Mean age 43<\/li>\n<li>Their triage approach\u00a0(different from US recommendations):\n<ul>\n<li>For intervention group (cytology plus HPV):\n<ul>\n<li>Normal HPV and cytology: repeat in 5 years<\/li>\n<li>At least\u00a0moderate dyskaryosis on cytology: colposcopy<\/li>\n<li>HPV positive, and neg or borderline\/mild dyskaryosis (eg ASCUS or LGSIL) on cytology: repeat HPV\/cytology at 6 and 18 months. refer to colposcopy if continued HPV positive or cytology worse<\/li>\n<\/ul>\n<\/li>\n<li>For control group (cytology only)\n<ul>\n<li>Normal cytology: cont routine screen<\/li>\n<li>At least\u00a0moderate dyskaryosis on cytology: colposcopy<\/li>\n<li>Borderline\/mild dyskaryosis (eg ASCUS or LGSIL) on cytology: repeat cytology at 6 and 18 months. refer to colposcopy if cytology same or\u00a0worse<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>Co-testing group: 20,490 of 21,623 women had double negative HPV\/cytology, 764 had\u00a0pos HPV\/neg cytology, 369 pos\u00a0cytology\/neg HPV<\/li>\n<li>Cytology only\u00a0group: 20,533 of 21,716 had negative cytology, 814 had pos HPV\/neg cytology (the HPV results were blinded), 369 pos\u00a0cytology\/neg HPV<\/li>\n<li>During 14 years of followup:\n<ul>\n<li>Co-testing: 149 CIN2, 152 CIN3 (including 5 adenoca in situ), 8 squamous cell and 6 adeno carcinomas<\/li>\n<li>Cytology only: 126 CIN2, 169 CIN3 (including 5 adenoca in situ),\u00a017 squamous cell and\u00a010 adeno carcinomas<\/li>\n<\/ul>\n<\/li>\n<li>Breakdown of the 14 year followup according to cytology and HPV status (again, HPV results were blinded for the control group)\n<ul>\n<li>Cancer:\n<ul>\n<li>Cytology neg\/HPV neg: 7 in intervention, 12 control; 3.3 vs 5.7\/100,000 women, incidence ratio 0.58 (0.23-1.48), nonsignficant<\/li>\n<li>Cytology neg\/HPV pos:\u00a04 in intervention,\u00a015 control;\u00a055.4 vs 190.9\/100,000 women, incidence ratio 0.29 (0.10-0.87)<\/li>\n<li>Cytology pos\/HPV neg: 3 in intervention,\u00a00 control;\u00a079.7 vs 13.4\/100,000 women, incidence ratio\u00a05.97 (0.30-119.22), nonsignficant [but they had to use 0.5 instead of\u00a00 for the cancer count, in order to do the math]<\/li>\n<\/ul>\n<\/li>\n<li>CIN3+ (the combination of cervical cancer and precancer):\n<ul>\n<li>Cytology neg\/HPV neg: 74 in intervention,\u00a086 control; 35.0 vs 40.7\/100,000 women, incidence ratio 0.86 (0.63-1.17), nonsignficant<\/li>\n<li>Cytology neg\/HPV pos:\u00a082 in intervention,\u00a094 control;\u00a01135.1 vs 1196.1\/100,000 women, incidence ratio 0.95 (0.71-1.28), nonsignificant<\/li>\n<li>Cytology pos\/HPV neg:\u00a010 in intervention,\u00a016 control;\u00a0265.7 vs 427.1\/100,000 women, incidence ratio\u00a00.62 (0.28-1.37), nonsignficant<\/li>\n<\/ul>\n<\/li>\n<li>The\u00a0cumulative incidence of cervical cancer 14 years after the initial\u00a0negative cytology\/negative HPV\u00a0screen in the co-testing group\u00a0(0.09%) was the same as\u00a0in the cytology negative patients\u00a0in the\u00a0cytology-only group <strong>after 9 years<\/strong><\/li>\n<li>The cumulative incidence of CIN3+ was 0.56% 14 years after the initial negative\/negative\u00a0screen in the co-testing group,\u00a0but 0.69%\u00a0in the cytology negative\u00a0patients\u00a0in the\u00a0cytology-only group <strong>after 9 years<\/strong><\/li>\n<li>Combining both groups, the incidence of CIN3+ was 72.1% lower (60.5-80.4%) in women &gt;40 years old vs younger; no statistically significant difference in cervical cancer<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>Commentary:<\/p>\n<ul>\n<li>Several studies have supported using only HPV screening without cytology (primary HPV screening) for detection of cervical dysplasia\/cancer (g., see doi.org\/10.1136\/bmj.e670 from BMJ or Ronco G. Lancet 2014; 383 (9916): 524); the latter study found that there was 60-70% better protection with primary HPV screening over cytology screening. And primary HPV screening might avoid over-referral to colposcopy and biopsies. And decrease the number of screens done\/longer intervals between screenings. Several countries now do primary HPV screening including Australia, Italy, Netherlands, New Zealand, Sweden and the UK.\u00a0The current study looked not just at cervical cancer, which may take years to manifest itself, but also to high-grade precancerous lesions (CIN3+) to try to ascertain if the longer screening interval could miss women with evolving cancers (which it didn&#8217;t: those with combined screening had the same incidence at 14 years as the cytology only group at 14 years).<\/li>\n<li>So, this study suggests several things:\n<ul>\n<li>It confirms\u00a0the superiority of HPV\/cytology\u00a0screening over cytology alone<\/li>\n<li>The very low incidence of CIN3+ in the overall combined groups (including the blinded HPV testing of the cytology-only group) who had\u00a0negative HPV testing (independent of cytology)\u00a0was quite low: 84 events in 20,859 patients (e.g., as compared to those who were HPV positive but cytology negative, with CIN3+ in 82 of 764 patients), affirming that HPV testing is superior to cytology testing<\/li>\n<li>The study also confirmed the utility of testing more than just the highest risk HPV 16\/18 types, since there were 30 of 501 patients with CIN3+ who were HPV positive\/cytology negative and HPV 16\/18 negative<\/li>\n<li>And the big conclusion was the very low risk of CIN3+ and cervical cancer itself\u00a0in patients who were &gt;40yo and had dually negative initial HPV\/cytology<\/li>\n<li>Putting this all together, in 2017 the Netherlands will implement the strategy of every 10-year screening for HPV negative women at least 40 years old<\/li>\n<\/ul>\n<\/li>\n<li>So, there really seems to be increasing data suggesting that primary HPV is a superior screening test (adding cytology seems to add more false positives than providing real clinical benefit), though i would imagine there need to be more studies in different populations to see what the optimal screening interval should be.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Cervical Cancer Screening Less Frequently?  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