Clinical Performance of Human Papillomavirus (HPV) Testing versus Cytology for Cervical Cancer Screening: Results of a Large Danish Implementation Study

Figures & data

Figure 1 Screening algorithms in the HPV- and cytology group of HPV SCREEN DENMARK.

Abbreviations: ASC-US, atypical squamous cells of undetermined significance; DNA, deoxyribonucleic acid; HPV, human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; mRNA, messenger ribonucleic acid.

Table 1 Characteristics of Women in HPV and Cytology Groups in the HPV SCREEN DENMARK Study

Characteristic	A. Invited population(n=35,081)				B. Screened population(n=28,352)
	HPV group		Cytology group		HPV group		Cytology group
	(n=14,104)		(n=20,977)		(n=11,339)		(n=17,013)
	n	%	n	%	n	%	n	%
Age^a
30–34	2,190	15.5	3,196	15.2	1,705	15.0	2,685	15.8
35–39	2,609	18.5	3,791	18.1	2,065	18.2	3,005	17.7
40–44	3,097	22.0	4,345	20.7	2,429	21.4	3,440	20.2
45–49	3,093	21.9	4,589	21.9	2,378	21.0	3,601	21.2
50–54	1,462	10.4	2,430	11.6	1,493	13.2	2,230	13.1
55–59	1,653	11.7	2,626	12.5	1,269	11.2	2,052	12.1
Median (IQR)	43 (37–49)		43 (37–49)		43 (37–49)		44 (37–50)
Educational level
Basic	2,228	15.8	3,438	16.4	1,510	13.3	2,356	13.8
Medium	5,560	39.4	8,332	39.7	4,443	39.2	6,727	39.5
High	6,001	42.5	8,831	42.1	5,247	46.3	7,752	45.6
Missing	315	2.2	376	1.8	139	1.2	178	1.0
Country of origin
Denmark	11,994	85.0	17,835	85.0	9,911	87.4	14,918	87.7
Immigrant	1,965	13.9	2,925	13.9	1,362	12.0	2,005	11.8
Descendant	56	0.4	115	0.5	46	0.4	75	0.4
Missing	89	0.6	102	0.5	20	0.2	15	0.1
Employment
Employed	10,945	77.6	15,403	73.4	9,232	81.4	13,176	77.4
Unemployed	2,824	20.0	5,006	23.9	1,905	16.8	3,428	20.1
Students	239	1.7	454	2.2	181	1.6	389	2.3
Missing	96	0.7	114	0.5	21	0.2	20	0.1
HPV vaccinated
Yes	1,234	8.8	1,915	9.1	1,247	11.0	1,928	11.3
No	12,870	91.3	19,062	90.9	10,092	89.0	15,085	88.7
Screened in previous screening round^b
Yes	11,103	78.7	16,616	79.2	9,904	87.3	14,788	86.9
No	3,001	21.3	4,361	20.8	1,435	12.7	2,225	13.1
History of cervical dysplasia
No prior CIN2+	13,249	93.9	19,660	93.7	10,322	91.0	15,584	91.6
Prior CIN2+	855	6.1	1,317	6.3	1,017	9.0	1,429	8.4

Notes: ^aFor invited population: age at invitation; For screened population: age at screening. ^bFor women aged 30–49 years: Screened during the past 4 years; For women aged 50–59 years: Screened during the past 6 years.

Abbreviations: CIN2+, cervical intraepithelial neoplasia grade 2 or worse; HPV, human papillomavirus, IQR, interquartile range.

Table 2 Odds Ratio of Screening Participation Within Six Months of Invitation in HPV Group and Cytology Group, Overall and by Age

Age	Group	N Invited for Screening	n (%) Screened		Model 1 (Crude)		Model 2 (Adjusted*)
					OR	(95% CI)	OR	(95% CI)
All	Cytology	20,977	12,327	(58.8)	1	(ref)	1	(ref)
	HPV	14,104	8241	(58.4)	0.99	(0.94–1.03)	0.97	(0.93–1.01)
30–39	Cytology	6987	3703	(53.0)	1	(ref)	1	(ref)
	HPV	4799	2477	(51.6)	0.95	(0.88–1.02)	0.93	(0.86–1.00)
40–49	Cytology	8934	5405	(60.5)	1	(ref)	1	(ref)
	HPV	6190	3800	(61.4)	1.04	(0.97–1.11)	1.01	(0.95–1.09)
50–59	Cytology	5056	3219	(63.7)	1	(ref)	1	(ref)
	HPV	3115	1964	(63.0)	0.97	(0.89–1.07)	0.95	(0.86–1.05)

Notes: *Adjusted for age, educational level, country of origin and employment status. A total of 691 women (2.0%) with missing values of adjustment variables excluded from model.

Abbreviations: CI, confidence interval; HPV, human papillomavirus; OR, odds ratio.

Figure 2 Flowchart of referrals and clinical outcomes among women screened by HPV testing or cytology during year 1 of the HPV SCREEN DENMARK study.

Abbreviations: AIS, adenocarcinoma in situ; ASCUS, atypical squamous cells of undetermined significance; CIN2, cervical intraepithelial neoplasia grade 2; CIN3, cervical intraepithelial neoplasia grade 3; DNA, deoxyribonucleic acid; HPV, human papillomavirus; hrHPV, high-risk human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; mRNA, messenger ribonucleic acid.

Table 3 Proportions and Odds Ratios of Referral to Colposcopy, Repeat Screening and Routine Screening in HPV and Cytology Groups, Overall and According to Age

Referral at Baseline	Age	HPV Group n=11,339		Cytology Group n=17,013		OR for HPV versus Cytology Group
						Model 1		Model 2
						(Crude)		(Adjusted*)
		n	(%)	n	(%)	OR	(95% CI)	OR	(95% CI)
New screen due to unsatisfactory test	All	8	(0.1)	117	(0.7)	0.10	(0.05–0.21)	0.11	(0.05–0.22)
	30–39	3	(0.1)	47	(0.8)	0.10	(0.03–0.31)	0.10	(0.03–0.33)
	40–49	3	(0.1)	40	(0.6)	0.11	(0.03–0.35)	0.11	(0.04–0.36)
	50–59	2	(0.1)	30	(0.7)	0.10	(0.03–0.43)	0.11	(0.03–0.44)
Colposcopy	All	436	(3.8)	362	(2.1)	1.84	(1.60–2.12)	1.88	(1.63–2.17)
	30–39	199	(5.3)	182	(3.2)	1.69	(1.37–2.07)	1.73	(1.41–2.13)
	40–49	162	(3.4)	128	(1.8)	1.88	(1.49–2.38)	1.94	(1.53–2.46)
	50–59	75	(2.7)	52	(1.2)	2.27	(1.59–3.25)	2.22	(1.55–3.17)
Repeat screening in 12 months	All	566	(5.0)	30	(0.2)	29.73	(20.58–42.96)	29.85	(20.65–43.14)
	30–39	236	(6.3)	12	(0.2)	31.59	(17.66–56.49)	31.44	(17.56–56.28)
	40–49	227	(4.7)	13	(0.2)	26.79	(15.30–46.91)	27.11	(15.48–47.48)
	50–59	103	(3.7)	5	(0.1)	33.12	(13.48–81.34)	32.78	(13.33–80.63)
Back to routine screening	All	10,329	(91.1)	16,504	(97.0)	0.32	(0.28–0.35)	0.31	(0.27–0.34)
	30–39	3332	(88.4)	5449	(95.8)	0.34	(0.29–0.40)	0.32	(0.28–0.38)
	40–49	4415	(91.8)	6860	(97.4)	0.30	(0.25–0.36)	0.29	(0.24–0.35)
	50–59	2582	(93.5)	4195	(98.0)	0.30	(0.23–0.39)	0.30	(0.23–0.39)

Notes: *Adjusted for age, educational level, country of origin and employment status; 317 women with missing values of adjustment variables excluded from models.

Abbreviations: CI, confidence interval; HPV, human papillomavirus; OR, odds ratio, PPV, positive predictive value.

Table 4 Detection of CIN2+ and CIN3+ Within Six Months of Follow-Up, in HPV and Cytology Group

Outcome	Age	% with CIN2+ or CIN3+ Detected						Odds Ratio of CIN2+ and CIN3+ Detection in HPV vs Cytology Group				PPV of Colposcopy Referral
		HPV Group			Cytology Group			Model 1 (Crude)		Model 2 (Adjusted*)		HPV Group			Cytology Group
		N	n	(%)	N	n	(%)	OR	(95% CI)	OR	(95% CI)	n/N	%	(95% CI)	n/N	%	(95% CI)
CIN2+	All	11,339	161	(1.4)	17,013	158	(0.9)	1.54	(1.23–1.92)	1.60	(1.28–2.00)	154/436	35.3	(30.8–39.8)	153/362	42.3	(37.2–47.4)
	30–39	3770	86	(2.3)	5690	89	(1.6)	1.47	(1.09–1.98)	1.54	(1.14–2.08)	83/199	41.7	(34.8–48.6)	86/182	47.3	(39.9–54.6)
	40–49	4807	57	(1.2)	7041	55	(0.8)	1.52	(1.05–2.21)	1.60	(1.09–2.33)	53/162	32.7	(25.4–40.0)	53/128	41.4	(32.8–50.1)
	50–59	2762	18	(0.7)	4282	14	(0.3)	2.00	(0.99–4.03)	1.97	(0.97–3.96)	18/75	24.0	(14.1–33.9)	14/52	26.9	(14.5–39.4)
CIN3+	All	11,339	110	(1.0)	17,013	117	(0.7)	1.42	(1.09–1.84)	1.47	(1.13–1.91)	107/436	24.5	(20.5–28.6)	115/362	31.8	(26.9–36.6)
	30–39	3770	62	(1.6)	5690	69	(1.2)	1.36	(0.96–1.92)	1.43	(1.01–2.03)	60/199	30.2	(23.7–36.6)	68/182	37.4	(30.3–44.5)
	40–49	4807	37	(0.8)	7041	37	(0.5)	1.47	(0.93–2.32)	1.52	(0.95–2.42)	36/162	22.2	(15.8–28.7)	36/128	28.1	(20.2–36.0)
	50–59	2762	11	(0.4)	4282	11	(0.3)	1.55	(0.67–3.59)	1.52	(0.66–3.51)	11/75	14.7	(6.5–22.9)	11/52	21.2	(9.7–32.6)

Notes: *Adjusted for age, educational level, country of origin and employment status; 317 (1.1%) women with missing values of adjustment variables excluded from models.

Abbreviations: CI, confidence interval; CIN2+, cervical intraepithelial neoplasia grade 2 or worse; CIN3+, cervical intraepithelial neoplasia grade 3 or worse; HPV, human papillomavirus; OR, odds ratio, PPV, positive predictive value.