Cervical cancer screening in immunosuppressed persons (other than PLHIV)

Cervical cancer (CC) is the fourth most common female cancer worldwide, and the twelfth most common in France (approximately 3,000 new cases per year and 800 deaths). Almost all cases are attributable to long-term human papilloma virus (HPV) infection. The French National Health Insurance Fund (CNAM) has requested the HAS to issue recommendations in relation to organised CC screening in immunosuppressed persons (other than PLHIV) in view of the increased risk of CC observed in this population.

Recommendation

The HAS points out firstly that primary prevention of genital HPV infection is based on universal vaccination. This vaccination is recommended in the general population for girls or boys starting at 11 years of age, with catch-up up to 26 years of age. Given that vaccination does not protect against all the potentially oncogenic types of HPV, and the duration of protection provided by these vaccines is not clearly established, particularly in immunosuppressed populations, HPV vaccination in no way dispenses with the need for CC screening and regular gynaecological follow-up. The screening procedure to be followed is the same for women who have had HPV vaccination and those who have not.

Thus, following its assessment, the HAS recommends more frequent cervical cancer screening, for the following immunosuppressed persons:

• living with primary or congenital immunodeficiency (e.g. DiGeorge syndrome, agammaglobulinaemia, hypogammaglobulinaemia, etc.)
• post-allogeneic haematopoietic stem cell transplantation;
• living with systemic lupus (treated or not);
• on immunosuppressive therapy for at least one year (e.g. organ transplantation, rheumatoid arthritis, IBD, multiple sclerosis, etc.)
• and any severely immunosuppressed person, diagnosed by a healthcare professional.

For these targeted persons, screening must start within one year following stem cell transplantation, systemic lupus diagnosis, or initiation of immunosuppressive therapy, including in women over 30 years of age whose most recent HPV test was negative prior to these situations.

Screening is recommended at the following intervals, for immunosuppressed persons (other than PLHIV):

• from 25 to 29 years of age, an annual cytology test is recommended.
• from 30 to 65 years of age, perform an initial HPV test at 30 years of age, and subsequently test every 3 years, if the test result is negative.
• from 65 years of age, the decision to continue or discontinue CC screening should be taken based on the most recent HPV test result and accounting for medical history

Implementation methods

To ensure equity of access throughout the country, cervical sampling may be carried out, as for the immunocompetent general population, by a gynaecologist, a general practitioner, or a midwife, and in pathology laboratories on medical prescription.

Screening should provide an opportunity to carry out (in the case of a general practitioner or gynaecologist) or refer for (in the case of other healthcare professionals) medical gynaecological follow-up required in immunosuppressed cases (particularly on account of a greater risk of other gynaecological conditions in this population).

In the event of an abnormal screening result, the healthcare professionals must ensure patient follow-up, referral and/or care.

Self-sampling is an alternative to cervical sampling by a healthcare professional for HPV testing for women from 30 years of age, previously unscreened or inadequately screened based on the recommended schedule, or in the specific case of reduced mobility (e.g. persons living with multiple sclerosis).

Need for information and communication

The HAS points out that good screening uptake will help lower the incidence of cervical cancer and the number of related deaths. Thus, it recommends to:

• conduct communication campaigns aimed at the target population and healthcare professionals in support of the updated cervical cancer screening regimen for immunosuppressed persons and issue reminders on the procedure to be followed in the event of an abnormal screening result;
• provide healthcare professionals with the necessary tools and resources to allow them to provide cervical cancer screening at the recommended intervals based on women’s age and immunological status.

The HAS adds that targeting immunosuppressed women concerned by this recommendation is a major challenge as regards sending out invitation letters at the recommended intervals to prevent any loss of chance.

Finally, the HAS strongly encourages the set-up of impact studies in order to measure i) the uptake rate among immunosuppressed women in the National cervical cancer screening programme, ii) the incidence of precancerous and cancerous lesions in immunosuppressed women according to the new recommendations, particularly to compare incidence based on immunosuppression profiles and age groups, and iii) the mortality rate from cervical cancer in immunosuppressed women.

The HAS may be required to review or specify its position based on impact study findings and the latest data available, particularly on the degree of immunosuppression induced by treatments.

 *Immunosuppressed persons concerned by this recommendation: post-organ transplantation (regardless of transplantation type) and on immunosuppressive therapy for at least one year; post-allogeneic haematopoietic stem cell transplantation; living with systemic lupus (treated or not); on immunosuppressive therapy for at least one year. Screening must start within one year following transplantation, systemic lupus or initiation of immunosuppressive therapy.

^α Negative result for intra-epithelial lesion or malignancy

^β Cervical screening in practice and Procedure to be followed for a woman who has an abnormal cervico-uterine cytology test, Thesaurus, Recommendations and guidelines collection, INCa, December 2016. Procedure to be followed for a woman who has an abnormal cervico-uterine cytology test (pending specific recommendations for the care of immunosuppressed persons)

This public health recommendation is intended for public decision-makers.