High concordance of results of testing for human papillomavirus in cervicovaginal samples collected by two methods, with comparison of a novel self-sampling device to a conventional endocervical brush

Abstract

A user-friendly self-sampling method for collecting representative cervical cell material would lower the threshold for women to respond to the invitation for cervical screening. In the present article, we introduce such a device; we have evaluated its sensitivity and specificity to detect high-grade cervical intraepithelial neoplasia (CIN), via high-risk human papillomavirus (hrHPV) detection and liquid-based cytology (LBC), compared to endocervical brush samples obtained by gynecologists. Women who had a cervical smear reading of moderate dyskaryosis or worse or a repeat equivocal Pap smear result in the cervical screening program (n=64) and healthy volunteers (n=32) took a self-obtained sample at home prior to their visit to the gynecological outpatient department. At the outpatient department, an endocervical brush smear was taken, followed by colposcopy and biopsy whenever applicable. Both self-obtained samples and endocervical brush samples were immediately collected in Surepath preservation solution and used for LBC and hrHPV testing (by general primer-mediated GP5+/6+PCR). hrHPV test results showed a good concordance between the two sample types (87%; kappa=0.71), with sensitivities for prevalent high-grade CIN that did not differ significantly (92% and 95%; P=1.0). The hrHPV test on self-obtained samples proved to be at least as sensitive for high-grade CIN as cytology on endocervical brush samples (34/37 versus 31/37; P=0.5). LBC showed a poor concordance between self-obtained and endocervical brush samples (60%; kappa=0.27). In conclusion, self-obtained samples taken by this novel device are highly representative of the hrHPV status of the cervix. In combination with hrHPV testing, the use of this device may have implications for increasing the attendance rate for cervical screening programs.

Figures

FIG. 1.

(A) The Mermaid cervicovaginal self-sampling method. The instrument comes ready-filled with 5 ml saline. After the insertion of the nozzle (N) into the vagina, the plunger (P) is pushed in order to release the saline via small holes in the nozzle (B) and rinse the upper vagina and the cervix. Then by releasing the plunger, the saline is aspirated back into the instrument. Upon removal of the instrument from the vagina, the saline now containing the sampled cells is released into a dedicated collection vial containing 10 ml SurePath fluid.

FIG. 2.

Representative thin layer sample pairs read as having conditions worse than BMD obtained from endocervical brush samples (A, C, and E) and the corresponding self-obtained samples (B, D, and F). (A through D) Objective, ×40; (E and F) objective, ×20.

FIG. 3.

A possible algorithm for follow-up of hrHPV positive self-obtained samples. These samples could be used for reflex cytology, and if this turns out to be abnormal, women should be referred for colposcopy-directed biopsy because the specificity of combined hrHPV testing and cytology on cervicovaginal self-obtained samples is quite high for CIN2, CIN3, and cervical cancer. If cytology of an hrHPV-positive cervicovaginal self-obtained sample is normal, an endocervical brush smear should be taken for cytology. If this smear is cytologically abnormal (BMD or worse dyskaryosis), referral for colposcopy is warranted. If the smear is cytologically normal, advisement for a repeat cervical smear after 1 year could be given for hrHPV testing and cytology. If this repeat smear is cytologically normal and hrHPV negative, women can go to the next screening round. Women should be referred for colposcopy-directed biopsy if the repeat smear is hrHPV positive and/or cytologically abnormal (BMD or worse dyskaryosis).