Detection of Carcinogenic Human Papillomavirus in Specimens Collected with a Novel Self-Sampling Device

We compared the detection of carcinogenic human papillomavirusDNA in cervicovaginal specimens self-collected using a noveldevice to the detection in physician-collected cervical specimensfrom 137 women. The kappa value was 0.66 (95% confidence interval,0.53 to 0.78), with an 83% overall test agreement and a 68%positive test agreement.

INTRODUCTION

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Introduction

Based on the central role of carcinogenic human papillomavirus(HPV) types in the development of cervical cancer (1, 3, 7)and its immediate precursor lesions (5), HPV testing has nowbeen approved in the United States as an adjunct to cytologyfor triage at all ages and for general screening in women aged30 years and older (8). One possible method to expand HPV-basedcervical cancer screening to underserved populations is self-collectionof cervicovaginal specimens. Numerous studies have evaluatedself-collection in combination with HPV DNA testing as a potentialalternative to cytology in low-resource settings. A new device(1a) was designed to physically mimic tampons and perhaps improvesampling of the cervix while minimizing sampling of the vagina.The self-sampling device has an ejectable tip, which is protectedduring insertion and removal by a retractable outer sheath.In this pilot validation study, we compare the detection ofcarcinogenic HPV DNA in cervicovaginal specimens self-collectedusing the Fournier device to detection in cervical specimenscollected from the cervix by a physician.

MATERIALS AND METHODS

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Materials and Methods

The study was carried out at the Department of Obstetrics andGynecology Division of Gynecologic Oncology at the Universityof Miami School of Medicine. The institutional review boardof the university approved the study. In total, 146 nonpregnant,nonhysterectomized women were recruited from the colposcopyand general gynecology clinics at Jackson Memorial Hospital,and 137 women (94%) agreed to participate and provided written,signed, informed consent. A research nurse assigned to the studyexplained the use of the self-sampling device (Fournier device)to the study subjects. A video demonstration was also shownto the study participants. Upon completion of the self-collection,women underwent a standard pelvic examination during which cervicalspecimens were collected using plastic disposable specula, cytobrushes,and Ayer's spatulas.

The tip of the self-sampling device was ejected into a vialcontaining a liquid-based cytology medium (SurePath; TriPath,Burlington, NC) and vortexed to release cells. Cytobrushes andAyer's spatulas were immersed and agitated in a separate vialcontaining the SurePath medium to release cells. Specimens werethen processed for the production of cytology slides accordingto the manufacturer's specifications.

HPV DNA testing. A Hybrid Capture 2 (HC2) (Digene Corporation, Gaithersburg,MD) test, a pooled-probe DNA test for one or more carcinogenicHPV types (HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56,-58, -59, and -68) (4), with probe set B was performed on residualSurePath specimens as previously described (6).

Statistical analysis. We calculated kappa values, overall agreement, and positiveagreement with 95% confidence intervals (95% CI). McNemar's ${chi}$ ² test was used to test for statistical differences (P <0.05) in HC2 positive test results between physician-collectedand self-collected specimens. We also compared the paired HC2results of the self-collected specimen and the physician-collectedspecimen to the cytology results from the physician-collectedspecimens.

RESULTS

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Results

Of 137 patients enrolled, 135 (99%) had complete data and wereincluded in this analysis. One-third (33%) of the women in thestudy sample were younger than 30 years of age and 18% wereolder than 49. Women were predominately African-American (44%)or Caucasian (49%). Two-thirds of the participants had completedhigh school or attended college, while 25% did not have anyformal education.

Table 1 summarizes the results of the HPV DNA testing of specimenscollected by the two methods. Sixty-one physician-collectedsamples (45%) and 58 patient-collected samples (43%) testedpositive by HC2 (P = 0.5, McNemar's ${chi}$ ²). The kappa value forthe HC2 test results on the paired specimens was 0.66 (95% CI,0.53 to 0.78), with an 83% overall agreement and a 68% positiveagreement.

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TABLE 1. Paired HC2 test results for physician-collected cervical specimens and self-collected cervicovaginal specimens collected using the Fournier sampler^a

A comparison of cytology and paired HC2 test results for physician-collectedand patient-collected specimens is shown in Table 2. There was75%, 100%, 83%, and 78% concordance of HC2 results for womenwith high-grade squamous intraepithelial lesions (HSIL), low-gradesquamous intraepithelial lesions (LSIL), atypical squamous cellsof undetermined significance (ASCUS), and negative cytology,respectively. Two (50%) of 4 patients with HSIL cytology, 22(88%) of 25 with LSIL cytology, 11 (37%) of 30 with ASCUS cytology,and 13 (17%) of 76 with negative cytology were HC2 positivefor both physician-collected and patient-collected specimens.Of the remaining two HSIL cases, one tested HC2 positive forthe physician-collected specimen but negative for the patient-collectedspecimen and the other tested negative by HC2 for both specimens.

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TABLE 2. Comparison of paired HC2 results to liquid-based cytology (SurePath) interpretations^a

DISCUSSION

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Discussion

We found a good concordance between test results of HC2, anFDA-approved test for carcinogenic HPV DNA, performed on cervicovaginalspecimens self-collected using the Fournier device and physician-collectedcervical specimens. Although this was a small sample of women,we suggest that this device might offer an acceptable alternativeto the relatively uncomfortable and costly traditional collectionmethod of undergoing a pelvic exam for the collection of a cervicalspecimen. Self-sampling can potentially reduce the patient timeand travel, with only women who test positive needing additionalclinical follow-up.

We note a couple of limitations for this pilot study. First,our limited sample size in this pilot study prevented us fromassessing the clinical performance for detection of histologicallyconfirmed precancer and cancer. The small number of HSILs, aless rigorous outcome, did not permit us to assess the relationshipbetween HPV testing of self-collected samples and HSIL cytology.Second, we did not alter the order of specimen collection, whichcould have introduced a systematic bias and reduced concordanceof HPV test results between the two specimens.

In summary, the good concordance with HPV DNA detection withthe referent standard, the cervical specimen collected by thephysician, and its acceptability suggest that the Fournier devicemay be a useful device for self-collection. However, largerstudies that include rigorous histologic endpoints and follow-upto overcome the insensitivities of colposcopy (2) are clearlyneeded to validate this device for screening. This device ismore complicated and expensive than using a simple Dacron swabor even a tampon for self-sampling, and increased performanceand acceptability must be demonstrated to warrant its use. Finally,cost utility analyses will also be needed to assess the viabilityof using this device in primary cervical cancer screening.

FOOTNOTES

* Corresponding author. Mailing address: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Room 7074, EPS MSC 7234, Bethesda, MD 20892-7234. Phone: (301) 435-3976. Fax: (301) 402-0916. E-mail: castlep{at}mail.nih.gov.

REFERENCES

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