Thursday, October 6, 2016

Cervical cancer screening interval can be extended beyond five years in HPV negative women.

 Clinical pearls:

  • Primary HPV testing provides better protection against cervical cancer than cytology screening tests.
  • HPV negative women who are at-least 40 years of age have a very low risk of cervical pathology and the screening interval can be increased to 10 years in Netherlands. All other women continued to be screened every 5 years.
  • HPV positive women, who are triage negative, or negative for HPV 16/18 genotyping have a very high risk of developing CIN3+ or cervical cancer, and the screening intervals cannot be extended beyond 5 years.
  • The use of HPV testing and age of the patient is the first step towards risk based screening.


Randomized control trials in the past have shown that HPV based screening provides a better protection against CIN3 than only cytology based screening.  Dutch researchers have reported the results of large population based study that confirms the findings from earlier studies. They suggest that cervical cancer screening interval for those women who test negative for HPV and are older (40+ years) can be safely extended from 5 to 10 years. All other women can get the screening at 5 years’ interval.

Separate screening intervals are defined for women who are HPV negative and those who were initially HPV positive but subsequent HPV negative after the triage test, because they face different risks for CIN3.[1]

Many countries (Australia, Italy, Netherlands, New Zealand, Sweden, and the UK) around the world have adopted or recommended HPV screening as the primary screening procedure and US still combines it with cytology.  When advocating for change in policies, the risk of interval cancer should also be taken into account. So longitudinal studies are required to document the incidence of long term cervical cancer.

New data analysis from the Netherlands was published in British Medical Journal, published 04 October 2016, suggest that the interval for cervical screening for HPV-negative individuals, older than 40 years) could be extended from 5 years to 10 years; all other women should continue to be screened every 5 years.[2]

The study is a population based 14 years follow up of cohorts from earlier POBASCAM randomized trial. (population based screening study Amsterdam). The follow up of 14 years comprised of three screening rounds first at baseline, then at five years and 10 years.

A total of 44 938 women aged between 29 and 61 were enrolled, 22 420 were randomized to the intervention group (cytology and HPV co-testing) and 22 518 to the control group (cytology with blinded HPV testing).

Follow up data was collected till year 2013, till that point of time every woman had the opportunity to undergo three rounds of 5-year screening.

Study results showed that the cumulative incidence of cervical cancer and CIN3+ among HPV negative women in the intervention group was similar to negative cytology in control group after two rounds of screening.

Cervical cancer and CIN risk ratios were .97 and .82 respectively.

In women with HPV negative and in the age range of 40+ years, the CIN3+ incidence was 72% lower as compared to younger women. (< .001). 

Women who were   HPV-positive but had negative results on HPV 16/18 genotyping and negative results on baseline and repeat cytology testing had 10.4 times the cumulative risk of developing CIN3 than HPV-negative women.

Similarly, HPV-positive women with negative cytology triage had 11.9-fold higher risk for developing cervical cancer than among HPV-negative women. After adding HPV 16/18 genotyping or repeat cytology as a triage test, only one cancer case was observed.

The study results show that HPV based screening programme provides a better protection as compared to cytology results. Long term incidences of cervical cancer and CIN3+ were low among HPV negative women in this study cohort, and supports an extension of the cervical screening interval beyond five years for women aged 40 years and older. 

HPV positive women with negative repeat cytology, HPV16/18 genotyping, and/or repeat cytology have at least a fivefold higher risk of CIN3+ than HPV negative women, indicating that HPV based screening programmes with long intervals (>five years) should be implemented with risk stratification according to the age of the patients. 





[1] Bulkmans NWJ, Berkhof J, Rozendaal L, et al. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet2007;370:1764-72.doi:10.1016/S0140-6736(07)61450-0 pmid:17919718.
[2] http://www.bmj.com/content/355/bmj.i4924

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