An exploration of individual- and population-level impact of the 2-dose HPV vaccination schedule in pre-adolescent girls

Figures & data

Figure 1. Countries that have implemented HPV vaccination in their National Immunization Program as of November 2015. Colors indicate the dosing schedules used. Primary sources used were the WHO vaccine-preventable diseases: monitoring system, HPV information center and the ECDC vaccination scheduler.^15-17 *Five countries recommend both the 2vHPV and the 4vHPV (2-dose schedule) in their program (Kenya, Malawi, Belgium, Hungary and Italy).

Table 1A. Geometric mean concentrations (GMC) for HPV16-specific antibodies after 3- and 2-dose schedules and corresponding ratios at different time points. GMCs for HPV16 after 3- and 2-dose schedules as reported in several studies and corresponding ratios for dividing 3-doses by 2-doses. Based on according-to-protocol analysis population, the GMC ratio shown in this table is calculated from the GMCs, as reported in the original papers; hence, small deviations might be present from the GMC ratios, as reported in these papers.

Vaccine	Study	Age group	N	GMC 3-dose (95% CI)	N	GMC 2-dose (95% CI)	Measured at	GMC ratio (95% CI) (3-dose/2-dose)	Assay
4vHPV	Dobson^19	9–13	251	7640 (6561–8896)	243	7457 (6388–8704)	7	1.02 (0.82–1.27)	cLIA
		16–26	246	3574 (3065–4169)			7	^*0.48 (0.39–0.60)
		9–13	98	1804 (1508 -2160)	96	1598 (1333–1916)	18	1.13 (0.87–1.46)
		16–26	92	837 (695–1008)			18	^*0.52 (0.40–0.68)
		9–13	186	1739 (1514–1998)	195	1414 (1235–1618)	24	1.23 (1.01–1.49)
		16–26	189	813 (709–933)			24	^*0.57 (0.47–0.70)
		9–13	83	1413 (1122–1780)	86	1151 (918–1444)	36	1.23 (0.89–1.70)
		16–26	86	678 (540–850)			36	^*0.59 (0.43–0.81)
4vHPV	Krajden^20	9–13	254	7332 (3641–13360)	251	8103 (3641–16318)	7	0.90 (0.34–2.44)	cLIA
		16–26	276	3641 (1808–7332)			7	^*0.45 (0.16–1.25)
		9–13	99	1998 (898–3641)	100	1480 (812–3641)	18	1.35 (0.48–3.77)
		16–26	96	812 (446–1480)			18	^*0.55 (0.21–1.43)
		9–13	187	1808 (898–3294)	200	1480 (735–2697)	24	1.22 (0.49–3.06)
		16–26	210	812 (446–1636)			24	^*0.55 (0.22–1.38)
		9–13	85	1636 (735–2981)	85	1480 (602–2441)	36	1.11 (0.41–2.97)
		16–26	99	735 (365–1636)			36	^*0.50 (0.18–1.39)
4vHPV	Hernandez-Avila^26	9–10	150	6539 (5220–8191)	145	5137 (4036–6538)	7	1.27 (0.92–1.77)	cLIA
		18–24	141	2409 (2004–2896)			7	^*0.47 (0.35–0.64)
		9–10	145	355 (289–435)	140	413 (338–504)	21	0.86 (0.65–1.14)
		18–24	134	276 (226–338)			21	^*0.67 (0.50–0.89)
4vHPV	Sankaranarayanan^33	10–18	1000	11 (10–12)	937	9 (8–10)	0 (day 1)	1.22 (1.06–1.41)	MFI
		10–18	308	5460 (5195–5738)	317	6125 (5785–6485)	7	0.89 (0.83–0.96)
		10–18	313	1209 (1105–1323)	314	1222 (1116–1338)	18	0.99 (0.87–1.12)
		10–18	271	221 (197–247)	278	163 (147–181)	36	1.36 (1.16–1.58)
		10–18	89	218 (181–262)	127	183 (160–209)	48	1.19 (0.95–1.50)
4vHPV	Leung^10	9–14	322	4807 (4421–5528)	327	5056 (4597–5562)	7	0.95 (0.82–1.10)	VLP-based ELISA
2vHPV		9–14			330	8244 (7678–8852)	7
4vHPV		9–14	315	1591 (1449–1748)	318	1285 (1151–1435)	12	1.24 (1.07–1.43)
2vHPV		9–14			325	2218 (2023–2431)	12
2vHPV	Lazcano-Ponce^21	9–10	416	18219 (16833–19720)	1016	10442 (9894–11020)	7	1.74 (1.59–1.92)	VLP-based ELISA
		18–24	317	6991 (6333–7717)			7	^*0.67 (0.60–0.75)
		9–10	408	2376 (2216–2547)	975	1432 (1357–1510)	21	1.66 (1.52–1.81)
		18–24	298	1035 (953–1125)			21	^*0.72 (0.65–0.80)
2vHPV	Romanowski 2011^24	9–14	67	22261 (18034–27480)	65	11067 (9190–13328)	7	2.01 (1.52–2.66)	VLP-based ELISA
		15–19	60	12858 (9696–17051)	62	8442 (6895–10336)	7	1.52 (1.08–2.16)
		20–25	51	7971 (5766–11020)	51	5673 (4377–7354)	7	1.41 (0.93–2.13)
		15–25	111	10332 (8329–12792)			7	^*0.93 (0.70–1.24)
		9–14	61	3606 (2738–4750)	63	1702 (1416–2045)	24	2.12 (1.52–2.95)
		15–25	101	1865 (1505–2311)			24	^*1.10 (0.83–1.45)
2vHPV	Romanowski 2014^23	9–14			53	1595 (1298–1960)	36		VLP-based ELISA
		15–25	85	1592 (1283–1976)			36	^*1.00 (0.74–1.35)
		9–14			53	1320 (1084–1607)	48
		15–25	80	1420 (1134–1777)			48	^*1.08 (0.80–1.45)
2vHPV	Romanowski 2015^22	9–14			45	1369 (1104–1698)	60
		15–25	79	1455 (1187–1782)			60
2vHPV	Safaeian^25	18–25	120	748 (648–867)	52	520 (422–641)	48	1.44 (1.12–1.85)	VLP-based ELISA
2vHPV	HPV-070^8	9–14			488	9400 (8818–10020)	7		VLP-based ELISA
		15–25	352	10234 (9258–11314)				^*1.09 (0.97–1.23)

* Immunobridging principle. The GMC ratio for antibody levels after 3 doses (in 15- to 25-year-old women) divided by 2 doses (in 9- to 14-year-old girls).

Table 1B. Geometric mean concentrations (GMC) for HPV18-specific antibodies after 3- and 2-dose schedules and corresponding ratios at different time points. GMCs for HPV18 after 3- and 2-dose schedules as reported in several studies and corresponding ratios for dividing 3-doses by 2-doses. Based on according-to-protocol analysis population, the GMC ratio shown in this table is calculated from the GMCs, as reported in the original papers; hence, small deviations might be present from the GMC ratios, as reported in these papers.

Vaccine	Study	Age group	N	GMC 3 dose (95% CI)	N	GMC 2 dose (95% CI)	Measured at	GMC ratio (95% CI) (3-dose/2-dose)	Assay
4vHPV	Dobson^19	9–13	252	1703 (1489–1946)	243	1207 (1054–1384)	7	1.41 (1.17–1.71)	cLIA
		16–26	264	661 (580–784)			7	^*0.55 (0.45–0.67)
		9–13	99	236 (184–304)	96	137 (106–177)	18	1.72 (1.20–2.47)
		16–26	95	74 (57–95)			18	^*0.54 (0.38–0.78)
		9–13	187	267 (220–234)	195	132 (109–160)	24	2.02 (1.67–2.46)
		16–26	202	91 (76–110)			24	^*0.69 (0.53–0.90)
		9–13	83	239 (175–327)	86	104 (77–141)	36	2.30 (1.49–3.55)
		16–26	96	71 (53–95)			36	^*0.68 (0.45–1.04)
4vHPV	Krajden^20	9–13	254	1808 (812–2981)	251	1212 (735–2441)	7	1.49 (0.62–3.61)	cLIA
		16–26	282	665 (299–1480)			7	^*0.55 (0.20–1.49)
		9–13	99	221 (110–545)	100	134 (81–270)	18	1.65 (0.61–4.49)
		16–26	98	99 (37–148)			18	^*0.74 (0.29–1.85)
		9–13	187	245 (122–665)	200	148 (67–230)	24	1.66 (0.58–4.72)
		16–26	215	110 (37–221)			24	^*0.74 (0.25–2.20)
		9–13	85	200 (99–545)	85	122 (55–270)	36	1.64 (0.51–5.26)
		16–26	102	90 (33–200)			36	^*0.74 (0.22–2.45)
4vHPV	Hernandez-Avila^26	9–10	150	1087 (891–1326)	145	605 (503–727)	7	1.80 (1.37–2.36)	cLIA
		18–24	141	344 (292–405)			7	^*0.57 (0.44–0.73)
		9–10	126	126 (105–151)	99	94 (76–115)	21	1.34 (1.02–1.77)
		18–24	77	74 (61–89)			21	^*0.79 (0.59–1.04)
4vHPV	Sankaranarayanan^33	10–18	1000	6 (5–7)	937	5 (4–5)	0 (day 1)	1.20 (0.98–1.47)	MFI
		10–18	308	2942 (2733–3167)	317	3068 (2812–3347)	7	0.96 (0.86–1.07)
		10–18	313	377 (337–422)	314	269 (241–299)	18	1.40 (1.20–1.64)
		10–18	271	184 (162–208)	278	117 (104–132)	36	1.57 (1.32–1.87)
		10–18	89	206 (165–257)	127	129 (111–151)	48	1.60 (1.22–2.09)
4vHPV	Leung^10	9–14	333	1654 (1484–1842)	331	1207 (1093–1333)	7	1.37 (1.18–1.59)	VLP-based ELISA
2vHPV		9–14			334	5277 (4859–5732)	7
4vHPV		9–14	326	477 (422–540)	322	264 (234–297)	12	1.81 (1.52–2.14)
2vHPV		9–14			328	1313 (1188–1451)	12
2vHPV	Lazcano-Ponce^21	9–10	416	8912(8198–9687)	1016	5876 (5517–6175)	7	1.53 (1.38–1.69)	VLP-based ELISA
		18–24	317	3483 (3164–3834)			7	^*0.60 (0.53–0.67)
		9–10	408	1036 (952–1127)	976	619 (583–657)	21	1.67 (1.51–1.86)
		18–24	298	438(395–485)			21	^*0.71 (0.63–0.80)
2vHPV	Romanowski 2011^24	9–14	68	7399 (6033–9073)	64	5510 (4646–6535)	7	1.34 (1.03–1.75)	VLP-based ELISA
		15–19	61	4845 (3740–6277)	63	5142 (4354–6072)	7	0.94 (0.69–1.28)
		20–25	53	3676 (2898–4664)	49	3523 (2514–4937)	7	1.04 (0.69–1.58)
		15–25	114	4262 (3572–5084)			7	^*0.77 (0.61–0.99)
		9–14	63	1102 (845–1436)	63	702 (563–876)	24	1.57 (1.11–2.22)
		15–25	103	728 (588–900)			24	^*1.04 (0.76–1.41)
2vHPV	Romanowski 2013^23	9–14			52	689 (530–896)	36		VLP-based ELISA
		15–25	81	712 (560–906)			36	^*1.03 (0.72–1.47)
		9–14			52	543 (427–691)	48
		15–25	79	605 (746–768)			48	^*1.11 (0.79–1.56)
2vHPV	Romanowski 2015^22	9–14			43	672 (476–826)	60
		15–25	76	635 (498–809)			60	^*0.94 (0.65–1.36)
2vHPV	Safaeian^25	18–25	120	335 (285–392)	52	305 (238–391)	48	1.10 (0.82–1.47)	VLP-based ELISA
2vHPV	HPV-070^8	9–14			493	5909 (5509–6638)	7		VLP-based ELISA
		15–25	382	5003 (4573–5473)				^*0.85 (0.76–0.95)

* Immunobridging principle. The GMC ratio for antibody levels after 3 doses (in 15- to 25-year-old women) divided by 2 doses (in 9- to 14-year-old girls).

Table 2. Incidence rate ratios of 3-dose compared with 2-dose incidence rates of genital warts after 4vHPV vaccination.

Study	Interval between doses	Age group	IRR (+95% CI) (3-dose/2-dose)	Adjusted IRR (+95% CI) (3-dose/2-dose)	Adjusted for
Blomberg et al.^42	Data for different intervals not shown. However, with increasing time between the doses, the differences between 3 and 2 doses decreased.	≤ 15 years	0.19 (0.08–0.46)	0.33 (0.13–0.85)	Age at vaccination, maternal educational level, disposable-income and calendar time
		16–17 years	0.23 (0.15–0.33)	0.35 (0.23–0.53)
		18–19 years	0.34 (0.24–0.48)	0.48 (0.34–0.68)
		20–21 years	0.35 (0.26–0.48)	0.49 (0.35–0.68)
		22–23 years	0.56 (0.40–0.79)	0.59 (0.42–0.83)
		24–27 years	0.66 (0.43–1.02)	0.56 (0.36–0.85)
		Total	0.46 (0.39–0.54)	0.53 (0.36–0.85)
Herweijer et al.^43	Not considered	10–16 years	0.63 (0.43–0.93)
		17–19 years	0.66 (0.45–0.95)
		10–19 y (Total)	0.63 (0.48–0.82)

Table 3A. Vaccine effectiveness for vaccine types HPV16 and HPV18 after 3- and 2-dose schedules compared with no vaccination after 2vHPV and 4vHPV vaccination.

Study	Vaccine	Age groups	Outcome	Proportion 3-dose (+95% CI)	Proportion 2-dose (+95% CI)	VE 3-dose (+95% CI)	VE 2-doses (+95% CI)	Proportion Two-dose (0,1 months) (+95% CI)	Proportion Two-dose (0,6 month ) (+95% CI)	VE 2-doses (0,1 month ) (+95% CI)	VE 3-doses (0,6 month) (+95% CI)
Kavanagh^46	2vHPV	20–21 years	HPV16/18 prevalence	13.6% (11.7–15.8%)	20.8% (14.1–29.4%)	54% (46–61%)	30% (−1–52%)
Kreimer – Costa Rica Vaccine Trial^44	2vHPV	18–25 years	12 month (incident) persistent HPV16/18 infection	0.85% (0.56–1.2%)	0.71% (0.18–1.9%)	81% ^1(71–87%)	84% ^1(46–95%)
Kreimer – Costa Rica Vaccine Trial/PATRICIA trial (modified total vaccinated cohort)^45	2vHPV	15–25 years	Incident detection HPV16/18	Rate per 100 PY 1.23 (1.12–1.34)	Rate per 100 PY 0.87 (0.56–1.29)	77% ^1 (75–79%)	76% ^1 (62–85%)	Rate per 100 PY 0.90 (0.49–1.53)	Rate per 100 PY 0.68 (0.17–1.85)	75% (54–88%)	83% (42–96%)
			Incident HPV16/18 detection, persisting for at least 6 months	Rate per 100 PY 0.26 (0.22–0.31)	Rate per 100 PY 0.16 (0.05–0.38)	89% ^1(87–91%)	90% ^1(73–97%)
			Incident HPV16/18 detection, persisting for at least 12 months	Rate per 100 PY 0.19 (0.15–0.24)	Rate per 100 PY 0.12 (0.03–0.32)	87% ^1 (84–90%)	90% ^1(69–98%)
Sankaranarayanan^33	4vHPV	10–18 years	Incident detection HPV16/18	0.4% (0.0–1.3%)				1.3% (0.6–2.4%)	0.8% (0.2–1.9%)
			Incident detection HPV6/11	0.2% (0.0–1.0%)				0.7% (0.2–1.6%)	0.2% (0.0–1.0%)

PY, person years. ¹Both vaccinated groups were compared to their own control group, composed of participants randomized for the control vaccine (Hepatitis A) who had received an equal number of doses.

Table 3B. Vaccine effectiveness for cross-protective types HPV31, HPV33 and HPV45 after 3- and 2-dose schedules compared with no vaccination after 2vHPV and 4vHPV vaccination.

Study	Vaccine	Outcome	Proportion 3-dose (+95% CI)	Proportion 2-dose (+95% CI)	VE 3-dose (+95% CI)	VE 2-dose (+95% CI)	Proportion Two-dose (0,1 month) (+95% CI)	Proportion Two-dose (0,6 month) (+95% CI)	VE 3-dose (0,1 month) (+95% CI)	VE 3-dose (0,6 month) (+95% CI)
Kavanagh^46	2vHPV	HPV31/33/45 prevalence	6.8% (5.5–8.5%)	7.5% (3.9–14.2%)	85% ^1 (81–88%)	83% ^1 (66–91%)
Kreimer – Costa Rica Vaccine Trial/ PATRICIA trial (modified total vaccinated cohort)^45	2vHPV	Incident one-time detection of HPV31/33/45	Rate per 100 PY 1.65 (1.53–1.78)	Rate per 100 PY 2.21 (1.68–2.85)	59.7% ^1 (56.0–63.0%)	37.7% ^1 (12.4–55.9%)
		Incident detection of HPV31/33/45 that persisted at least 6 months	Rate per 100 PY 0.61 (0.54–0.69)	Rate per 100 PY 0.71 (0.43–1.09)	60.1% ^1 (54.0–65.4%)	30.7% ^1 (-27.9–63.0%)	Rate per 100 PY 2.76 (1.96–3.78)	Rate per 100 PY 3.07 (2.21–4.18)	10% (−42–43%)	68% (27–87%)
		Incident detection of HPV31/33/45 that persisted at least 12 months	Rate per 100 PY 0.40 (0.34–0.46)	Rate per 100 PY 0.43 (0.23–0.74)	54.9% ^1 (46.2–62.3%)	7.6% ^1 (−118 - 61%)
Sankaranarayanan^33	4vHPV	Incident detection HPV31/33/45	6.0% (4.1–8.3%)				4.6% (3.2–6.4%)	4.9% (3.3–7.2%)

PY, person years. ¹Both vaccinated groups were compared to their own control group, composed of participants randomized for the control vaccine (Hepatitis A) who had received an equal number of doses.

Table 4. Vaccine effectiveness (VE) of different dosing schedules on cervical precursor lesions.

Study	Vaccine	Design	Age groups	Endpoint	Effect estimate	Adjusted for	Adjusted effect estimate 3-doses^*	Adjusted effect estimate 2-doses^*
Brotherton et al. (Vaccination before first screen) ^46	4vHPV	Data-linkage	12–26 years	Any high grade	Hazard Ratio	Age in 2007, remoteness and SES	0.71 (0.64–0.80)	1.21 (1.02–1.44)
				CIN3/AIS			0.69 (0.58–0.81)	1.17 (0.92–1.48)
				CIN2			0.75 (0.65–0.86)	1.22 (0.97–1.54)
				High-grade cytology			0.53 (0.47–0.60)	0.63 (0.50–0.80)
				Low-grade cytology			0.73 (0.68–0.78)	0.52 (0.44–0.61)
Crowe et al. (all ages) ^47	4vHPV	Data-linkage	11–27 years	High-grade cases	Odds Ratio	SES, remoteness, year of birth, quartile of follow-up times	0.54 (0.43–0.67)	0.79 (0.64–0.98)
				Other cases			0.66 (0.62–0.70)	0.79 (0.74–0.85)
Gertig et al. ^48	4vHPV	Data-linkage	12–17 years	Any high grade	Hazard ratio	Remoteness, SES and age at first screening	0.61 (0.48–0.78)	1.02 (0.68–1.53)
				CIN3/AIS			0.53 (0.36–0.77)	0.87 (0.46–1.67)
				CIN2			0.70 (0.52–0.94)	0.99 (0.59–1.64)
				CIN1			0.82 (0.66–1.0)	0.90 (0.61–1.33)
				High-grade cytology			0.71 (0.61–0.83)	0.95 (0.73–1.23)
				Low-grade cytology			0.79 (0.75–0.84)	0.64 (0.57–0.72)
Pollock et al. ^49	2vHPV	Data-linkage	20–21 years	CIN 3	Risk Ratio	Cohort year, deprivation score and age in months	0.45 (0.35–0.58)	0.77 (0.49–1.21)
				CIN 2			0.5 (0.40–0.63)	0.81 (0.54–1.22)
				CIN1			0.71 (0.58–0.87)	0.65 (0.42–1.01)

* The reported effect estimates are relative to the unvaccinated. A ratio below 1 indicates a protective effect of vaccination on cervical precursor lesions. The closer the effect estimate is to 0, the lower is the risk for a cervical precursor lesion.

Dobson SR, Mcneil S, Dionne M, Dawar M, Ogilvie G, Krajden M, Sauvageau C, Scheifele DW, Kollmann TR, Halperin SA, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA 2013; 309(17):1793–802; PMID:23632723.

 PubMed Web of Science ®Google Scholar

Krajden M, Cook D, Yu A, Chow R, Su Q, Mei W, Mcneil S, Money D, Dionne M, Palefsky J, et al. Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization, Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial. Vaccine 2014; 32(5):624–30; PMID:24055350; http://dx.doi.org/10.1016/j.vaccine.2013.09.007

 PubMed Web of Science ®Google Scholar

Hernandez-Avila M, Torres L, Stanley M, Salmeron J, Cruz-Valdez A, Munoz N, Herrero R, Villasenor-Ruiz IF, Lazcano-Ponce E. Evaluation of the immunogenicity of the quadrivalent HPV vaccine using two versus three doses at month 21: An epidemiological surveillance mechanism for alternate vaccination schemes. Hum Vaccin Immunother, 2016; 12(1):30-8; http://dx.doi.org/10.1080/21645515.2015.1058458

 PubMed Web of Science ®Google Scholar

Sankaranarayanan R, Prabhu PR, Pawlita M, Gheit T, Bhatla N, Muwonge R, Nene BM, Esmy PO, Joshi S, Poli UR, et al. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol 2015.

 Web of Science ®Google Scholar

Leung TF, Liu AP, Lim FS, Thollot F, Oh HM, Lee BW, Rombo L, Tan NC, Rouzier R, Friel D, et al. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9–14 years: Results to month 12 from a randomized trial. Hum Vaccin Immunother 2015; 11(7):1689–702; PMID:26062002; http://dx.doi.org/10.1080/21645515.2015.1050570

 PubMed Web of Science ®Google Scholar

Lazcano-Ponce E, Stanley M, Munoz N, Torres L, Cruz-Valdez A, Salmeron J, Rojas R, Herrero R, Hernandez-Avila M. Overcoming barriers to HPV vaccination: non-inferiority of antibody response to human papillomavirus 16/18 vaccine in adolescents vaccinated with a two-dose vs. a three-dose schedule at 21 months. Vaccine 2014; 32(6):725–32; PMID:24355090; http://dx.doi.org/10.1016/j.vaccine.2013.11.059

 PubMed Web of Science ®Google Scholar

Romanowski B, Schwarz TF, Ferguson LM, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Catteau G, Dobbelaere K, et al. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum Vaccin 2011; 7(12):1374–86; PMID:22048171; http://dx.doi.org/10.4161/hv.7.12.18322

 PubMed Web of Science ®Google Scholar

Romanowski B, Schwarz TF, Ferguson LM, Ferguson M, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Behre U, et al. Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination: results from a randomized study. Hum Vaccin Immunother 2014; 10(5):1155–65; PMID:24576907; http://dx.doi.org/10.4161/hv.28022

 PubMed Web of Science ®Google Scholar

Romanowski B, Schwarz TF, Ferguson L, Peters K, Dionne M, Behre U, Schulze K, Hillemanns P, Suryakiran P, Thomas F, et al. Sustained Immunogenicity of the HPV-16/18 AS04-Adjuvanted Vaccine Administered as a Two-Dose Schedule in Adolescent Girls: Five-Year Clinical Data and Modelling Predictions from a randomized study. Hum Vaccin Immunother. 2016 Jan 2; 12(1):20-9’’, For 47 via Science Direct’’Papillomavirus Research Volume 1, December 2015, Pages 59–73.

 Google Scholar

Safaeian M, Porras C, Pan Y, Kreimer A, Schiller JT, Gonzalez P, Lowy DR, Wacholder S, Schiffman M, Rodriguez AC, et al. Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial. Cancer Prev Res (Phila) 2013; 6(11):1242–50; PMID:24189371; http://dx.doi.org/10.1158/1940-6207.CAPR-13-0203

 PubMed Web of Science ®Google Scholar

European Medicines Agency, Assessment report Cervarix. 2013.

 Google Scholar

Blomberg M, Dehlendorff C, Sand C, Kjaer SK. Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts: A Nationwide Study of 550 000 Young Girls. Clin Infect Dis 2015; 61(5):676–82; PMID:25944340; http://dx.doi.org/10.1093/cid/civ364

 PubMed Web of Science ®Google Scholar

Herweijer E, Leval A, Ploner A, Eloranta S, Simard JF, Dillner J, Netterlid E, Sparen P, Arnheim-Dahlstrom L Association of varying number of doses of quadrivalent human papillomavirus vaccine with incidence of condyloma. JAMA 2014; 311(6):597–603; PMID:24519299; http://dx.doi.org/10.1001/jama.2014.95

 PubMed Web of Science ®Google Scholar

Kavanagh K, Pollock KG, Potts A, Love J, Cuschieri K, Cubie H, Robertson C, Donaghy M. Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types. Br J Cancer 2014; 110(11):2804–11; http://dx.doi.org/10.1038/bjc.2014.198

 PubMed Web of Science ®Google Scholar

Kreimer AR, Rodriguez AC, Hildesheim A, Herrero R, Porras C, Schiffman M, Gonzalez P, Solomon D, Jimenez S, Schiller JT, et al. Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. J Natl Cancer Inst 2011; 103(19):1444–51; PMID:21908768; http://dx.doi.org/10.1093/jnci/djr319

 PubMed Web of Science ®Google Scholar

Kreimer AR, Struyf F, Del Rosario-Raymundo MR, Hildesheim A, Skinner SR, Wacholder S, Garland SM, Herrero R, David MP, Wheeler CM, et al. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA trials. Lancet Oncol 2015; 16(7):775–86; PMID:26071347; http://dx.doi.org/10.1016/S1470-2045(15)00047-9

 PubMed Web of Science ®Google Scholar

Brotherton JM, Malloy M, Budd AC, Saville AM, Drennan K, Gertig DM. Effectiveness of less than three doses of quadrivalent human papillomavirus vaccine against cervical intraepithelial neoplasia when administered using a standard dose spacing schedule: Observational cohort of young women in Australia. Papillomavirus Research, 2015.

 Google Scholar

Crowe E, Pandeya N, Brotherton JM, Dobson AJ, Kisely S, Lambert SB, Whiteman DC. Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical abnormalities: case-control study nested within a population based screening programme in Australia. BMJ 2014; 348:g1458; http://dx.doi.org/10.1136/bmj.g1458

 PubMed Web of Science ®Google Scholar

Gertig DM, Brotherton JM, Budd AC, Drennan K, Chappell G, Saville AM, Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. BMC Med 2013; 11:227; PMID:24148310; http://dx.doi.org/10.1186/1741-7015-11-227

 PubMed Web of Science ®Google Scholar