Human papillomavirus genotype-specific risks for cervical intraepithelial lesions

Figures & data

Table 1. Distribution of participants by age at screening, country, and corresponding cytology abnormalities in Denmark, Iceland, Norway, and Sweden, in 2006–2008

	Nordic Countries
	Denmark		Iceland		Norway		Sweden		Total		Cervical intraepithelial lesion
Age group	N	(%)	N	(%)	N	(%)	N	(%)	N	(%)	Normal^a	Low-grade^b	High-grade^c
18–23	271	(11.7)	498	(21.6)	649	(32.9)	330	(18.7)	1748	(20.9)	1498	221	29
24–26	556	(24.0)	363	(15.7)	382	(19.4)	479	(27.1)	1780	(21.3)	1531	190	59
27–29	353	(15.2)	251	(10.9)	130	(6.6)	114	(6.5)	848	(10.1)	749	73	26
30–34	394	(17.0)	393	(17.0)	242	(12.3)	180	(10.2)	1209	(14.5)	1118	65	26
35–39	259	(11.2)	381	(16.5)	248	(12.6)	218	(12.3)	1106	(13.2)	1030	52	24
40–51	486	(21.0)	424	(18.4)	321	(16.3)	445	(25.2)	1676	(20.0)	1598	60	18
Total	2319		2310		1972		1766		8367		7524	661	182

^aNegative for intraepithelial lesions or malignancy.

^bAtypical squamous intraepithelial lesion or low-grade squamous intraepithelial lesion.

^cAtypical squamous cells cannot rule out high-grade lesion, high-grade squamous intraepithelial lesion, adenocarcinoma in situ, or cervical cancer.

Table 2. Weighted prevalence^a of 40 HPV types measured, carcinogenic HPV^b, non-carcinogenic HPV^c, the 5 most common HPV types in declining order, vaccine-targeted carcinogenic HPV types in combination^d,e,f, and a hypothetical prevalence of remaining carcinogenic HPVs if vaccine-targeted HPVs would be eliminated^g,h, by age group

Age groups	18–23 n = 1748	24–26 n = 1780	27–29 n = 848	30–34 n = 1209	35–39 n = 1106	40–51 n = 1676		Total n = 8367
Prevalence of HPV types
Any HPV  95% CI	56.7% 53.8–59.6	47.1% 44.4–9.8	36.2% 32.2–40.4	26.4% 23.3–29.7	17.7% 14.9–20.7	12.6% 10.8–14.6		25.3% 24.1–26.5
Carcinogenic HPV^b  95% CI	46.2% 43.3–49.0	36.6% 34.1–39.2	25.8% 22.3–29.6	19.5% 16.8–22.5	11.8% 9.5–14.4	7.3% 5.9–8.9		18.1% 17.1–19.1
non-carcinogenic HPV^c	30.0% 27.5–32.7	22.5% 20.4–24.8	16.9% 13.8–20.3	10.6% 8.6–13.0	7.7% 5.8–9.9	6.4% 5.1–7.9		11.8% 11.0–12.7
The five most common HPV types in declining order
1^st most prevalent HPV type  % (95% CI)	HPV 16 14.2 (12.3–16.2)	HPV 16 11.4 (9.8–13.1)	HPV 16 8.3 (6.1–10.9)	HPV 16 4.6 (3.3–6.4)	HPV 16 3.2 (2.0–4.8)	HPV 70 1.5 (0.9–2.4)		HPV 16 4.9 (4.4–5.5)
2^nd most prevalent HPV type  % (95% CI)	HPV 31 9.3 (7.8–11.1)	HPV 31 6.6 (5.4–8.0)	HPV 42 5.3 (3.7–7.4)	HPV 52 3.6 (2.4–5.0)	HPV 42 2.0 (1.0–3.5)	HPV 16 1.1 (0.6–1.9)		HPV 31 2.9 (2.5–3.3)
3^rd most prevalent HPV type  % (95% CI)	HPV 42 8.5 (7.0–10.1)	HPV 52 6.0 (4.8–7.3)	HPV 31 4.1 (2.8–5.9)	HPV 31 3.0 (1.9–4.5)	HPV 52 1.8 (1.0–2.9)	HPV 42 0.9 (0.5–1.6)		HPV 42 2.9 (2.4–3.3)
4^th most prevalent HPV type  % (95% CI)	HPV 51 8.5 (7.1–10.2)	HPV 42 5.8 (4.6–7.2)	HPV 52 3.9 (2.4–5.8)	HPV 39 2.2 (1.2–3.5)	HPV 31 1.8 (1.0–3.1)	HPV 52 0.9 (0.5–1.6)		HPV 52 2.8 (2.4–3.3)
5^th most prevalent HPV type  % (95% CI)	HPV 56 7.5 (6.1–9.1)	HPV 18 4.6 (3.6–5.9)	HPV 45 3.3 (2.0–5.2)	HPV 42 2.1 (1.2–3.4)	HPV 18 1.6 (0.8–3.0)	HPV 39 0.9 (0.4–1.6)		HPV 56 2.0 (1.7–2.4)
HPV types targeted by HPV vaccines
2-valent^d  16, 18	19.7% 17.6–22.0	15.6% 13.7–17.5	10.0% 7.6–12.8	6.3% 4.7–8.2	4.6% 3.1–6.5	1.5% 0.9–2.4		6.6% 5.9–7.2
4-valent^e  6,11,16,18	23.8% 21.5–26.2	17.4% 15.5–19.5	11.9% 9.2–15.0	6.8% 5.2–8.8	5.4% 3.8–7.4	2.3% 1.6–3.3		7.8% 7.1–8.5
9-valent^f  6,11,16,18,31,33,45,52,58	36.6% 33.9–39.4	29.6% 27.3–32.1	22.3% 18.9–26.0	14.9% 12.5–17.6	10.0% 7.9–12.5	5.1% 3.9–6.5		14.4% 13.5–15.4
Prevalence of the carcinogenic HPV types after removing those targeted by HPV vaccines
2 v and 4 v vaccine^g  31,33,35,39,45,51,52,56,58,59,68	37.1% 34.4–39.9	28.5% 26.2–31.0	20.4% 17.2–23.9	14.8% 12.3–17.5	8.4% 6.5–10.6		6.2% 4.9–7.7	14.2% 13.3–15.1
9 v vaccine^h  35,39,51,56,59,68	23.2% 20.9–25.6	16.0% 14.2–18.0	10.0% 7.7–12.7	7.1% 5.4–9.2	3.5% 2.3–5.1		3.4% 2.5–4.6	7.5% 6.8–8.2

^aThe prevalence of HPV is estimated as the number of positive specimens for a given HPV type (or combination of HPV types) divided by the total number of specimens with a valid PCR result, for each stratum. Weighting was performed for the sampling fractions (Supplementary Table 1).

^bCarcinogenic HPV is defined as positive to one of the HPV types 16,18,31,33,35,39,45,51,52,56,58,59,68.

^cNon-carcinogenic HPV is defined as positive to one of the HPV types 6,11,26,30,32,40,42,43,44,53,54,55,61,62,66,67,69,70,73,74,81,83,86,87,89,90,91.

^dHPV types included in 2 valent vaccine HPV16, 18

^eHPV types included in 4 valent vaccine, HPV6,11.16,18

^fHPV types included in 9 valent vaccine, HPV6,11,16,18,31,33,45,52,58

^gPrevalence of the carcinogenic HPV types after removing those targeted by HPV vaccines, HPV31,33,35,39,45,51,52,56,58,59,68

^hHPV 35,39,51,56,59,68

Abbreviations: CI = confidence interval; HPV = human papillomavirus.

Figure 1. The age-specific prevalence of carcinogenic HPV types and non-carcinogenic HPV types among those with normal cytology. Abbreviation: HPV = human papillomavirus

Table 3. Positive predictive value^a for concomitant low-grade and high-grade cytology, combined as carcinogenic HPV^b, 2 v and 4v HPV Vaccine vaccine-targeted carcinogenic HPV types in combination ^c, HPV types targeted by 9valent HPV vaccine^d, 27 non-carcinogenic HPV types^g and age

Age groups	18–23	24–26	27–29	30–34	35–39	40–51		Total
Carcinogenic HPV
#	860	705	253	253	147	147	2365
PPV for Low-grade cytology  95% CI	22.1% 19.4–25.0	20.6% 17.6–23.7	22.1% 17.2–27.8	18.6% 14.0–23.9	19.0% 13.0–26.3	20.4% 14.2–27.8	21.0% 19.3–22.7
PPV for High-grade cytology  95% CI	3.0% 2.0–4.4	7.5% 5.7–9.7	9.1% 5.9–13.3	9.1% 5.9–13.3	14.3% 9.1–21.0	7.5% 3.8–13.0	6.6% 5.7–7.7
Carcinogenic HPV types targeted by 2 v HPV or 4v vaccines^c, HPV16,18
#	372	292	94	84	46	33		921
PPV for Low-grade cytology 95% CI	23.9% 19.7–28.6	20.2% 15.8–25.3	21.3% 13.5–30.9	21.4% 13.2–31.7	15.2% 6.3–28.9	24.2% 11.1–42.3		21.8% 19.2–24.6
PPV for High-grade cytology 95% CI	4.3% 2.5–6.9	12.3% 8.8–16.7	17.0% 10.1–26.2	16.7% 9.4–26.4	21.7% 10.9–36.4	9.1% 1.9–24.3		10.3% 8.4–12.5
Carcinogenic HPV types targeted by 9v vaccines^d, HPV16, 18, 31, 33,45,52,58
#	668	553	202	181	112	92		1808
PPV for Low-grade cytology  95% CI	22.0% 18.9–25.3	21.0% 17.7–24.6	21.8% 16.3–28.1	18.8% 13.4–25.2	23.2% 15.8–32.1	20.7% 12.9–30.4		21.3% 19.5–23.3
PPV for High-grade cytology  95% CI	3.4% 2.2–5.1	9.4% 7.1–12.1	10.4% 6.6–15.5	11.0% 6.9–16.5	17.0% 10.5–25.2	9.8% 4.6–17.8		8.0% 6.8–9.3
Remaining carcinogenic HPV types after excluding those targeted by 2v and 4v HPV vaccines^e, HPV31,33,35,39,45,51,52,56,58,59,68
#	488	413	159	169	101	114		1444
PPV for Low-grade cytology  95% CI	20.7% 17.2–24.6	20.8% 17.0–25.1	22.6% 16.4–29.9	17.2% 11.8–23.7	20.8% 13.4–30.0	19.3% 12.5–27.7		20.4% 18.4–22.6
PPV for High-grade cytology  95% CI	2.0% 1.0–3.7	4.1% 2.4–6.5	4.4% 1.8–8.9	5.3% 2.5–9.9	10.9% 5.6–18.7	7.0% 3.1–13.4		4.3% 3.3–5.5
Remaining carcinogenic HPV types after excluding these HPV types which are targeted by 9v HPV vaccines^f, HPV35,39,51,56,59,68
#	192	152	51	72	35	55		557
PPV for Low-grade cytology  95% CI	22.4% 16.7–29.0	19.1% 13.2–26.2	23.5% 12.8–37.5	18.1% 10.0–28.9	5.7% 0.7–19.2	20.0% 10.4–33		19.7% 16.5–23.3
PPV for High-grade cytology  95% CI	1.6% 0.3–4.5	0.7% 0.0–3.6	3.9% 0.5–13.5	4.2% 0.9–11.7	5.7% 0.7–19.2	3.6% 0.4–12.5		2.3% 1.2–4.0
27 non-carcinogenic HPV types^g
#	551	426	157	135	95	115		1479
PPV for Low-grade cytology  95% CI	20.5% 17.2–24.1	20.9% 17.1–25.1	18.5% 12.7–25.4	17.0% 11.1–24.5	16.8% 9.9–25.9	11.3% 6.2–18.6		19.1% 17.2–21.2
PPV for High-grade cytology  95% CI	1.3% 0.5–2.6	3.8% 2.2–6.0	3.8% 1.4–8.1	5.2% 2.1–10.4	2.1% 0.3–7.4	4.3% 1.4–9.9		2.9% 2.1–3.9

^aPositive predictive value was estimated as the number of specimens of a given cytology category positive to an HPV type (or combination of types) divided by the total number of specimens positive to the same HPV type (or combination of types) irrespective of cytology category.

^bCarcinogenic HPV is defined as positive to one of the HPV types 16,18,31,33,35,39,45,51,52,56,58,59,68.

^cCarcinogenic HPV types included in 2valent or 4valent HPV vaccine, HPV16, 18

^dHPV types included in 9valent HPV vaccine, HPV16,18,31,33,45,52,58

^eRemaining of 13 carcinogenic HPV types after removing those targeted by 2valent and 4valent HPV vaccines, HPV31,33,35,39,45,51,52,56,58,59,68

^fRemaining of 13 carcinogenic HPV types after removing those targeted by 9valent HPV vaccines, HPV35,39,51,56,59,68

^g27 non-carcinogenic HPV is defined as positive to one of the HPV types 6,11,26,30,32,40,42,43,44,53,54,55,61,62,66,67,69,70,73,74,81,83,86,87,89,90,91.

Abbreviations: PPV = Positive predictive value, CI = confidence interval; HPV = human papillomavirus.

Figure 2. Adjusted odds ratios with 95% CIs for high-grade (A) and low-grade (B) cytology diagnoses among women positive to specified HPV type with HPV infection of the specified type compared with women having normal cytology. Carcinogenic HPV types are marked in red. Abbreviations: CI = confidence interval; HPV = human papillomavirus; OR = odds ratio