Role and uptake of human papillomavirus vaccine in adolescent health in the United States

Figures & data

Figure 1 Major cancers attributable to HPV infection. Seven cancers are associated with HPV infection, total attributable risk to any HPV infection is shown with blue color referring to HPV types 16 and 18 and the remaining due to other HPV infection (in red).

Note: Based on data excerpted from Parkin et al.⁹⁷
Abbreviation: HPV, human papillomavirus.

Table 1 New cases of HPV-related major cancers in the USA and worldwide^42,100,101

	Percentage of all cancers caused by HPV	New cases per year USA/worldwide	Median age of diagnosis (years)
Cervix	3.18	12,280/53,000	47
Vaginal	0.12	2300/13,200	69
Vulval	0.12	3900/26,800	70
Anal	0.23	5260/99,000	62
Penal	0.06	1250/21,100	57
Oral cavity	0.07	10,840/183,100	67
Oropharynx	0.05	12,660/27,700	64

Abbreviation: HPV, human papillomavirus.

Table 2 Comparison of two HPV vaccines with regard to efficacy, safety, and immunogenicity trial data key to FDA licensure^102,103

	Cervarix® PATRICIA HPV types 16 and 18		Gardasil® Phase II/III data HPV types 6, 11, 16, and 18
	Females aged (96.1% CI)a 10–25 years		Females aged 16–26 years (95% CI)b					Males aged 16–26 years (95% CI)
All combined HPV vaccine specific types	CIN 1+ or AIS	CIN 2/3 or AIS	CIN 1+ or AIS	CIN 2/3 or AIS (HPV 16/18)	VIN 2/3 (HPV 16/18)	VaIN 2/3 (HPV 16/18)	Genital warts	External genital lesions	Genital warts	AIN 1/2/3c
Percent efficacy for 3 doses (ATPd/PPEe)	93 (80,98)	92 (82,97)	96 (92,98)	98 (94,100)	100 (56,100)	100 (50,100)	99 (96,100)	91 (70,98)	89 (66,98)	78 (40,93)
Percent efficacy for ≥ 1 dosef	97 (89,99)	98 (90,100)	95 (92,97)	97 (93,99)	97 (82,100)	97 (82,100)	96 (93,98)	76 (56,88)	80 (60,91)	77 (51,90)
Percent reduction regardless of HPV 16/18 exposureg	56 (43,65)	53 (38,65)	62 (55,67)	52 (41,61)	73 (50,90)	73 (50,90)	80 (74,85)	67 (48,79)	68 (49,81)	50 (26,67)
Duration of vaccine induced anti-HPV (GMTs)	Titers to HPV 16 and 18 peaked at month 7 and 18, reached a plateau sustained to month 76		Titers to HPV 6, 11, 16, and 18 peaked at month 7 after the initial vaccine dose, declined through month 24, then stabilized, and were similar at month 60					Titers to HPV 6, 11, 16, and 18 peaked at month 7 after the initial vaccine dose; GMTs declined through month 24 and stabilized through month 36 at levels above baseline.
Serious adverse eventsh	5.3% of vaccines and 5.9% of controls		0.8% of vaccines and 1.0% of controls

Notes:

a The 96.1% confidence interval analysis results from a statistical adjustment from a previously conducted interim analysis;

b combined protocols which was prospectively planned and included use of similar study entry criteria;

c represents MSM Sub-Study for Vaccine HPV Types Population;

d ATP (According to Protocol Cohort; Cervarix) – women who had normal cytology, ASCUS, or LSIL at baseline) who received three doses of vaccine and were HPV DNA negative and seronegative at baseline and HPV DNA negative at month 6 for the corresponding HPV type;

e PPE (per protocol population, Gardasil) received all three vaccinations within 1 year of enrollment, did not have major deviations from the study protocol, and were naïve (PCR negative and seronegative to HPV Types 6, 11, 16, and 18 prior to dose 1 and through 1 month post dose 3 (month 7);

f subjects who received at least one dose of vaccine, who were HPV-naïve (ie, seronegative and PCR negative) at day 1 the vaccine HPV type being analyzed. (Cervarix population also were negative to all 14 oncogenic HPV types and who had normal cytology), case counting started at day 1;

g includes all vaccinated subjects described in ^firrespective of HPV DNA status and serostatus at baseline;

h for all combined study populations controlled and uncontrolled; Gardasil reports are for serious systemic adverse events. The information in this table have been based on multiple resources.^102,103 Table does not include disease due to nonvaccine types.

Abbreviations: CI, confidence interval; AIS, adenocarcinoma in situ; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; VIN, vulvar intraepithelial neoplasia; VaIN, vaginal intraepithelial neoplasia; AIN, anal intraepithelial neoplasia; GMT, geometric mean titer; PCR, polymerase chain reaction; DNA, deoxyribonucleic acid; MSM, men having sex with men; ASCUS, atypical squamous cells of undermined significance; LSIL, low grade squamous intraepithelial lesion; FDA, US Food and Drug Administration; PATRICIA, Papilloma TRIal Cervical cancer in young Adults.

Table 3 US HPV vaccine licensure and recommended schedules^{23,83,102–105}

	Cervarix® HPV types 16 and 18	Gardasil® HPV types 6, 11, 16, and 18
	Females		Males
FDA licensure and usage for vaccination	Age 10–25 years for:	Age 9–26 years for:	Age 9–26 years for:
	• Cervical cancer	• Cervical cancer	• Genital warts (HPV types 6 and 11)
	• CIN Grades 2 or worse and AIS	• CIN Grade 1, CIN Grade 2 or worse and AIS	• Anal cancer and associated precancerous lesions (HPV types 6, 11, 16, and 18)
	• CIN Grade 1	• Condylomata acuminata
		• VIN grade 2 and grade 3	• CIN Grades 2 or worse and AIS
		• VaIN grade 2 and grade 3	• CIN Grade 1
		• Anal precancerous lesions and cancer (HPV types 6, 11, 16, and 18)
ACIP guidelines		For prevention of cervical cancers, precancers, and genital warts	May be administered to reduce the likelihood of genital warts
	• Either vaccine is recommended for the prevention of cervical precancers, cancers, and genital warts
	• Females as young as 9 years eligible
	• Females aged 11–12 for routine HPV vaccination
	• Females aged 13–18 for catch up vaccination
Dosing	A complete series is three doses; the second dose should be administered 1–2 months after the frist dose; the third dose should be administered 6 months after the frist dose
Cost	Approximately $384 (approximately $184 per dose × three doses)
Special situations	• Can be administered to females who have abnormalities on their cervical cancer screening or to those with active or past history of genital warts; vaccine can protect against infection with HPV vaccine types not already acquired.
	• Prevaccination assessments such as Papanicolau testing, screening for high-risk HPV DNA, or serologic testing are not indicated.
	• Safe in lactating women
Immunocompromised individuals	Vaccines can be administered to individuals who are immunosuppressed from disease or medications, but the immune response and vaccine efficacy may be less than that in immunocompetent individuals
Not recommended	Pregnant women and women above the age of 26 years

Note: Information based on multiple resources.^{23,83,102–105}

Abbreviations: ACIP, Advisory Committee of Immunization Practices; FDA, US Food and Drug Administration; HPV, human papillomavirus; AIS, cervical adenocarcinoma in situ; CIN, cervical intraepithelial neoplasia; VIN, vulvar intraepithelial neoplasia; VaIN, vaginal intraepithelial neoplasia.

Figure 2 HPV vaccine coverage (in percent) for 13–17-year-old adolescents by race/ethnicity for at least one dose and for complete three doses. The percent coverage is based on data on either Gardasil® or Cervarix® vaccine among 9621 females. Persons who identified as Native Hawaiian or other Pacific Islanders and persons of multiple races were categorized as other.

Notes: Excerpted from the 2009 National Immunization Survey-Teen.^60,98 Adapted from Centers for Disease Control and Prevention. National, state, and local area vaccination coverage among adolescents aged 13–17 years – United States, 2009. MMWR 2010;59:1018–1023 and Centers for Disease Control and Prevention. 2009 NIS-Teen Vaccination Coverage Table Data; 2011.
Abbreviations: HPV, human papillomavirus; AI, American Indian; AN, Alaskan Natives.

Figure 3 HPV vaccination uptake in 13–17-year-old adolescents by state in the USA. Estimated percent coverage for (A) first dose of the HPV vaccine and (B) all three doses of the HPV vaccine.

Notes: Based on data excerpted from the 2009 National Immunization Survey-Teen.^60,98 Adapted from Centers for Disease Control and Prevention. National, state, and local area vaccination coverage among adolescents aged 13–17 years – United States, 2009. MMWR 2010;59:1018–1023 and Centers for Disease Control and Prevention. 2009 NIS-Teen Vaccination Coverage Table Data; 2011.
Abbreviation: HPV, human papilloma virus.

Figure 4 Financial sources among adolescents receiving HPV vaccine. Vaccine is mostly covered by individual insurance, Vaccine for Children (VFC) program (those on Medicaid, uninsured, American Indian or Alaskan Native or underinsured), and Federally Qualified Health Centers.

Notes: Based on data excerpted from the 2009 National Immunization Survey-Teen;⁹⁹ adapted from Centers for Disease Control and Prevention. National, state, and local area vaccination coverage among adolescent aged 13–17 years – United States, 2008. MMWR Morb Mortal Wkly Rep. 2009;58(36):997–1001. Data are presented as percentages.
Abbreviation: HPV, human papillomavirus.

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