Clinical Laboratory Experience with Cervista HPV HR as a Function of Cytological Classification: Comparison with Retrospective digene HC2 High-Risk HPV DNA Test Data

LETTER

Kinney et al. (1) signaled caution over a purported increased rate of high-risk human papillomavirus (HPV) DNA detection from liquid-based cytology collections (ThinPrep; Cytyc Corporation, Marlborough, MA) with Cervista HPV HR (Cervista; Hologic, Madison, WI) compared to the rate using the digene HC2 High-risk HPV DNA test (HC2; Qiagen, Gaithersburg, MD). Other studies published from a laboratory (2–6) or clinical (7) perspective do not reflect this opinion. In this letter, we compare a large data set generated from consecutive 9-month intervals of HC2 and Cervista screening, stratified by age and cytological classification.

(The results of this work were previously presented, in part, at the 59th Annual Scientific Meeting of the American Society for Cytopathology, Baltimore, MD, 4 to 8 November 2011.)

Prior to July 2009, high-risk HPV screening was performed with HC2 at a reference laboratory. Beginning in July 2009, high-risk HPV detection was performed by Wheaton Franciscan Laboratory utilizing Cervista according to the package insert protocol (6, 8). In an institutional review board-approved protocol, an 18-month review of all HPV screenings was executed (October 2008 through March 2010). All cytological screening was derived from ThinPrep collection; processing and analysis were performed by Wheaton Franciscan Laboratory cytologists during the combined interval. The significance test of proportions (two-proportion Z-ratio) determined if differences in cytological classification or detection rate were significant.

Of specimens sufficient for screening within the first 9-month interval (n = 2,386), 80.2% of cytological assessments were negative for intraepithelial lesions or malignancy (NILM), while 16.7% yielded a diagnosis of atypical squamous cells of undetermined significance (ASC-US). The ASC-US and NILM rates from evaluable specimens (n = 2,400) changed inversely within the second 9-month interval (P ≤ 0.0002) (Table 1). Despite a higher rate of ASC-US during the Cervista testing interval, the HPV detection rates within ASC-US and NILM classifications revealed no significant differences from those during the HC2 testing interval (P ≥ 0.14) (Table 2). A secondary calendar-matched 5-month review of HPV detection within NILM and ASC-US classifications, when stratified by age, extended these findings (Table 3).

Table 1.

Cytological classification of specimens yielding an evaluable HPV screening result for consecutive 9-month intervals in which HC2 or Cervista was utilized

Cytology diagnosisa	% of specimens with diagnosis		P value
	HC2, 2008-2009 (n = 2,386)	Cervista, 2009-2010 (n = 2,400)
NILM	80.2	73.7	<0.0002
ASC-US	16.7	22.8	<0.0002
LSIL	1.8	2.4	0.17
HSIL	0.8	0.4	0.13
Unsatisfactory for cytology	0.5	0.7	0.47

^aLSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion.

Table 2.

HPV DNA detection percentage, delineated by cytology diagnosis, from consecutive 9-month intervals of HC2 and Cervista screening

Cytology diagnosis	% of specimens in which HPV DNA was detecteda		P value
	HC2, 2008-2009b	Cervista, 2009-2010c
NILM	7.7	9.1	0.14
ASC-US	43.0	40.3	0.41
LSIL	79.5	79.3	0.98
HSIL	72.2	70.0	0.90
Unsatisfactory for cytology	0.0	0.0	NDd

^aPercentages are specific to cytology diagnosis.

^bThere were 2,386 total determinations.

^cThere were 2,400 attempted determinations; 20 specimens yielded indeterminate results by Cervista (16 NILM, 1 ASC-US, and 3 unsatisfactory).

^dND, not determined.

Table 3.

Comparison of HPV DNA detection by HC2 and Cervista, stratified by patient age and cytology diagnosis, for calendar-matched 5-month intervals

Age range	NILM				ASC-US
	No. of specimens (range)	% with HPV detected		P value	No. of specimens (range)	% with HPV detected		P value
		HC2	Cervista			HC2	Cervista
<30	55–68	21.8	16.2	0.42	111–148	61.3	54.1	0.24
30–39	362–375	11.7	10.5	0.59	43–75	41.9	40.0	0.84
40–49	310–328	4.6	8.4	0.05	42–61	31.1	23.8	0.42
50–59	243–282	5.0	7.0	0.32	22–29	9.1	13.7	0.61
>60	113–128	3.4	9.4	0.06	8–9	25.0	11.1	0.45
≥30	1,043–1,101	7.0	8.9	0.10	134–155	30.6	29.0	0.77
Total	1,111–1,156	7.7	9.4	0.16	245–303	44.5	41.3	0.45

Castle et al. (9) reported a 7.8% rate of HC2 reactivity to nontargeted and noncarcinogenic HPV types in ASC-US patients. Laboratory comparisons of Cervista and HC2 reported a trend toward increased HC2 detection rates from ASC-US patients. Such detection percentages via HC2 and Cervista ranged from 42.9 to 50.5% and 36.4 to 48.4%, respectively (4, 6). Improved Cervista specificity within data sets not delineated by cytological classification was noted in additional tandem comparisons with HC2 (2, 3, 5).

Recent guidelines advocate adjunctive HPV screening in women aged ≥30 years regardless of cytological result (10). Kinney et al. (1) reviewed Cervista data which suggested detection rates of >18% in NILM patients aged ≥30 years. Furthermore, the detection rate was 18.4% in patients aged ≥60 years. In contrast, our comparison of over 1,000 retrospective HC2 results from NILM patients aged ≥30 years to approximately 1,100 results generated by Cervista showed no difference in rates of detection (P = 0.10) (Table 3). Moreover, the overall Cervista detection rates in NILM patients (9.4%) and NILM patients aged ≥50 years (7.8%) are similar to the rates from a meta-analysis of NILM patients (11.3%) and NILM patients aged ≥54 years (∼10%) (11).

In conclusion, HPV detection rates, when stratified by cytological classification and age of patient, did not differ significantly between HC2 and Cervista screening. The opinions of Kinney et al. (1) were derived from a didactic review of Cervista data (8). The contrasting data reported here were obtained from “real-world performance” (1) and suggest that Cervista and HC2 assays adjunctively contribute to cervical cancer triage in equivalent fashion.