Evaluation of human papillomavirus (HPV) tests for primary screening of precancerous and cancerous lesions of the cervix and the role of p16/Ki67 dual immunostaining
The present recommendations concern immunocompetent women eligible for cervical cancer screening, aged between 25 and 65, who have not undergone total hysterectomy. Based on current knowledge, the screening recommandation will be the same, irrespective of whether women have been vaccinated against HPV or not.
- Maintenance of cervical cancer screening procedures and triage strategies for women aged 25 to < 30 years
- between the ages of 25 and 30, cervical cancer screening continues to be based on the use of two cytology tests one year apart, then after 3 years if the results of the first two are normal;
- in this context, liquid-based cytology is recommended: collection in a liquid medium makes it possible to perform an HPV test on the same sample (reflex test), and avoids the need to recall women for collection of a second sample in the event of an abnormal result, as would be the case for a conventional Pap smear;
- the INCa recommendations on the management of women with an abnormal cervical cytology result apply1.
- Modification of cervical cancer screening procedures for women aged 30 to 65 years
- from the age of 30 years, the HAS recommends that the HPV test replace cytology as the primary cervical screening test;
- based on current cervical cancer screening guidelines, which recommend three-yearly cytology testing between the ages of 25 and 30 years, HPV tests in women from the age of 30 will be performed 3 years after the last normal cytology test;
- the interval between two HPV screening tests is 5 years, as long as tests are negative.
- Self-collected vaginal sampling: an alternative to collection of cervical samples by a health professional for an HPV test for certain women
Self-collected vaginal sampling should be offered, from the age of 30, to women who are not screened or who are inadequately screened: it facilitates the screening of women who never undergo screening or who are underscreened.
- Triage strategies for women with a positive HPV test
For women aged 30 to 65 years, in whom an HPV test has been used for primary cervical screening, a twostage triage strategy is recommended. After a positive HPV test, a reflex cytology test should be performed:
- if the cytology result is ASCUS or more severe abnormalities, women should be recalled for a colposcopy;
- if the cytology result is negative, an HPV test is performed one year later (see algorithm). If this triage HPV test performed one year later is positive a colposcopy should be performed; if this triage HPV test is negative, a new HPV screening test should be done 5 years later.
- Role of p16/Ki67 dual immunostaining in the cervical cancer screening strategy
In view of the available data, the use of p16/Ki67 dual immunostaining for primary screening or as a triage test following a positive HPV test is not recommended.
Triage algorithm for women aged 30 to 65 years to whom an HPV test has been proposed for primary cervical cancer screening
Global preventive stratégy
Cervical cancer screening must be part of a global preventive strategy incorporating all the methods of prevention. In particular, this strategy is based on vaccination, the early treatment of precancerous lesions and the appropriate and rapid treatment and management of women with cervical cancer.
Since the Ministerial Order of 4 May 2018, cervical cancer screening in France has been based on an organised national screening programme. The national screening programme is based on current French guidelines for cervical cancer screening, i.e., cytology testing in asymptomatic women aged 25 to 65 years every 3 years, following two consecutive normal tests performed one year apart. In its 2010 guidelines, the HAS considered that switching to the HPV test as a screening test was premature but might ultimately be implemented once organised screening was in place, particularly in terms of coverage and quality assurance measures. Guaranteeing the quality of the cervical cancer screening programme is crucial insofar as this programme is aimed at populations who are not ill and given that it presents associated risks (particularly in terms of unnecessary procedures), is funded collectively and should make it possible to offer treatment of equivalent quality to all participating women, across the whole territory.
In view of the changing context of cervical cancer screening in France and the availability of new scientific data, the Directorate General for Health requested that HAS evaluate the role of the HPV test and the use of p16/Ki67 dual immunostaining in the primary screening strategy for precancerous and cancerous lesions of the cervix.