cervical cancer screening less frequently than every 5 years??

A recent review of cervical HPV screenings in the Netherlands found that those with negative screening could potentially be screened less frequently than every 5 years (see pap screening more than q5 yrs bmj2016in dropbox, or doi.org/10.1136/bmj.i4924​). details:

--43,339 women aged 29-61 with a negative HPV and/or cytology were randomly assigned to HPV and cytology co-testing (intervention group) or 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.
--mean age 43
--their triage approach (different from US recommendations):
    --for intervention group (cytology plus HPV):
        --normal HPV and cytology: repeat in 5 years
        --at least moderate dyskaryosis on cytology: colposcopy
        --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
    --for control group (cytology only)
       --normal cytology: cont routine screen
       --at least moderate dyskaryosis on cytology: colposcopy
       --borderline/mild dyskaryosis (eg ASCUS or LGSIL) on cytology: repeat cytology at 6 and 18 months. refer to colposcopy if cytology same or worse

results:
--co-testing group: 20,490 of 21,623 women had double negative HPV/cytology, 764 had pos HPV/neg cytology, 369 pos cytology/neg HPV
​--cytology only group: 20,533 of 21,716 had negative cytology, 814 had pos HPV/neg cytology (the HPV results were blinded), 369 pos cytology/neg HPV
--during 14 years of followup:
    --co-testing: 149 CIN2, 152 CIN3 (including 5 adenoca in situ), 8 squamous cell and 6 adeno carcinomas
    --cytology only: 126 CIN2, 169 CIN3 (including 5 adenoca in situ), 17 squamous cell and 10 adeno carcinomas
--breakdown of the 14 year followup according to cytology and HPV status (again, HPV results were blinded for the control group)
    --cancer:
        --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
        --cytology neg/HPV pos: 4 in intervention, 15 control; 55.4 vs 190.9/100,000 women, incidence ratio 0.29 (0.10-0.87)
        --cytology pos/HPV neg: 3 in intervention, 0 control; 79.7 vs 13.4/100,000 women, incidence ratio 5.97 (0.30-119.22), nonsignficant [but they had to use 0.5 instead of 0 for the cancer count, in order to do the math]  
    --CIN3+ (the combination of cervical cancer and precancer):
        --cytology neg/HPV neg: 74 in intervention, 86 control; 35.0 vs 40.7/100,000 women, incidence ratio 0.86 (0.63-1.17), nonsignficant
        --cytology neg/HPV pos: 82 in intervention, 94 control; 1135.1 vs 1196.1/100,000 women, incidence ratio 0.95 (0.71-1.28), nonsignificant
        --cytology pos/HPV neg: 10 in intervention, 16 control; 265.7 vs 427.1/100,000 women, incidence ratio 0.62 (0.28-1.37), nonsignficant
--the cumulative incidence of cervical cancer 14 years after the initial negative cytology/negative HPV screen in the co-testing group (0.09%) was the same as in the cytology negative patients in the cytology-only group after 9 years
--the cumulative incidence of CIN3+ was 0.56% 14 years after the initial negative/negative screen in the co-testing group, but 0.69% in the cytology negative patients in the cytology-only group after 9 years
--combining both groups, the incidence of CIN3+ was 72.1% lower (60.5-80.4%) in women >40 years old vs younger; no statistically significant difference in cervical cancer

Commentary:
--several studies have supported using only HPV screening without cytology (primary HPV screening) for detection of cervical dysplasia/cancer (eg, 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. The 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't: those with combined screening had the same incidence at 14 years as the cytology only group at 14 years).
--so, this study suggests several things:
    --it confirms the superiority of HPV/cytology screening over cytology alone
    --the very low incidence of CIN3+ in the overall combined groups (including the blinded HPV testing of the cytology-only group) who had negative HPV testing (independent of cytology) was quite low: 84 events in 20,859 patients (eg, 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
    ​--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
    --and the big conclusion was the very low risk of CIN3+ and cervical cancer itself in patients who were >40yo and had dually negative initial HPV/cytology
    --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
--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.