CLINICAL OBSTETRICS AND GYNECOLOGY Volume 57, Number 2, 256–278 r 2014, Lippincott Williams & Wilkins
Primary Strategies for HPV Infection and Cervical Cancer Prevention DIANE M. HARPER, MD, MPH, MS,* and LESLIE R. DEMARS, MDw *Departments of Family and Geriatric Medicine, Obstetrics and Gynecology, Bioengineering, Epidemiology and Population Health, Health Promotion and Behavioral Sciences, University of Louisville School of Medicine, Louisville, Kentucky; and wDepartment of Obstetrics and Gynecology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
Abstract: Counseling messages for tobacco cessation, condom use, circumcision, and selective choice in the number of sexual partners can help reduce the risk of cervical cancer. Other sexual behavioral and reproductive risk factors for cervical cancer are a younger age at first intercourse and at first full-term pregnancy as well as increasing duration of combined hormonal oral contraceptive use. Micronutrients and supplements can reduce the risk of human papillomavirus infection, persistence, progression, and regression. Some human papillomavirus infections can be prevented by vaccination. Cervical cancer is best prevented by screening. Key words: HPV vaccines, efficacy, immune titers, dosing schedule
Prophylactic HPV Vaccines Human papillomavirus (HPV) is a double-stranded, about 8000-bp, DNA virus that has 2 late transcription regions and 7 early transcription regions as well as regulatory regions. The first late region, L1, produces a protein that represents the outermost coat of the virus. HPV vaccines contain replicates of the L1 protein called virus-like particles (VLPs) that are type specific (Table 1). In addition, each vaccine has its own adjuvant used to promote the durability of the immune response. There are 2 prophylactic HPV vaccines currently registered with national and international regulatory bodies: Cervarix and Gardasil/Silgard; in addition, Gardasil has added 5 additional oncogenic types against which it offered no original protection as a next-generation L1 VLP
Correspondence: Diane M. Harper, MD, MPH, MS, Departments of Family and Geriatric Medicine, Obstetrics and Gynecology, Bioengineering, Epidemiology and Population Health, Health Promotion and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY. E-mail: diane.m.harper@ gmail.com The authors declare that they have nothing to disclose. CLINICAL OBSTETRICS AND GYNECOLOGY
256 | www.clinicalobgyn.com
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VOLUME 57
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JUNE 2014
Primary Prevention for Cervical Cancer and HPV TABLE 1.
Composition of 3 Prophylactic HPV Vaccines Cervarix34
HPV VLP protein content
Total L1 VLP protein content Adjuvant
257
Gardasil/Silgard35
Gardasil+ 516
HPV 16
20 mg
HPV 16
40 mg
HPV 16
60 mg
HPV 18
20 mg
HPV 18 HPV 6 HPV 11
20 mg 20 mg 40 mg
HPV 18 HPV 31 HPV 33 HPV 45 HPV 52 HPV 58 HPV 6 HPV 11
40 mg 20 mg 20 mg 20 mg 20 mg 20 mg 30 mg 40 mg 270 mg
225 mg Aluminum hydroxyphosphate sulfate
500 mg
40 mg
120 mg
3-O-desacyl-4-mono- 50 mg phosphoryl lipid A Aluminum hydroxide 500 mg Aluminum salt hydroxyphosphate sulfate
HPV indicates human papillomavirus; VLP, virus-like particle.
vaccine (Table 1). All vaccines have proven efficacy against type-specific HPV infections.1 None of the vaccines has proven efficacy against any HPV-associated cancer and will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.2 Unlike cervical cancer, there are no secondary screening tests universally acknowledged to detect HPV-associated precancers of the head and neck, penis, anus, vulva, or vagina.3 In the setting of effective cervical cytology screening programs, prophylactic HPV vaccines will prevent some abnormal cytologic changes as well as some cervical intraepithelial neoplasia grade 3 (CIN 3) diseases, thereby preventing the need for surgical treatment of the CIN 3 precancer. This review will provide specific data for the 2 approved prophylactic vaccines, and where data are available, the nonavalent ‘‘Gardasil+ 5’’ vaccine data for efficacy and immunogenicity. All efficacy studies to date show that prevention of type-specific HPV infections is most easily accomplished by type-specific vaccination before HPV infection. Both
Cervarix and Gardasil are effective in populations that have already been sexually active or exposed to HPV, but at a lesser efficacy compared with populations that are naive to the HPV types before vaccination.4,5 Gardasil efficacy in males is restricted to short follow-up times and more rapid loss of antibody titers than seen in females6; there are no efficacy studies of Cervarix in males.
The Focus on Cervical Cancer Prevention of cervical cancer has focused on the identification of cervical cancer precursors with cytologic screening and the treatment of high-grade precancerous lesions. With this model, the incidence of cervical cancer in the United States has decreased by 80% since the widespread adoption of Pap testing.7 There are 2 main histologic categories of cervical cancer: squamous cell and adenocarcinoma. The majority of the cancers are squamous, starting at the transformation zone of the cervix, detectable with cervical samplings at the time of Pap testing, www.clinicalobgyn.com
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and usually visible at colposcopy.8 Adenocarcinoma, in contrast, develops in the glandular cells of the endocervix, is harder to detect by cytology, harder to detect by colposcopy, presents at later stages, and is associated with a higher mortality.9 Because of the effectiveness of cytologic screening and treatment for squamous cell precursors, the proportion of adenocarcinoma and adenocarcinoma in situ cancers diagnosed is increasing. As with squamous cell cancers, the most common HPV types associated with adenocarcinoma include HPV 16, 18, and 45.10 Although Pap testing remains the best way to detect squamous cervical cancer precursors, a convincing argument for HPV vaccination would be the prevention of adenocarcinomas and their precursor lesion, adenocarcinoma in situ. This would elevate the HPV vaccine discussion above the economic evaluation of costeffectiveness within a screening program. Economic analyses have shown that US cervical cancer prevention and treatment accounts for 92% of the HPVrelated economic burden with 8% allocated to the costs for care and prevention of vulvar, vaginal, penile, anal, oropharyngeal, and mouth cancers as well as juvenile-onset recurrent respiratory papillomatosis and anogenital warts.11,12 Specific models of HPV vaccination strategies have consistently shown that the duration of vaccine protection is one of the most potent predictors of cancer TABLE 2.
reduction; no cancer prevention is possible if vaccination efficacy is not maintained for at least 15 years without waning.13–15 Although the incidence of noncervical diseases may eventually be reduced with vaccination, it is a small highlight economically compared with what needs to be done to prevent HPV cervical disease in the United States and globally.
Reduction in Cytologic Cervical Abnormalities and Surgical Treatments Both vaccines provide some level of efficacy against those HPV infections that persist to cause cytologic abnormalities and subsequent excisional therapies for high-grade precancerous lesions. Table 2 details the differences in these efficacies between Cervarix and Gardasil. In the HPV-naive population, Cervarix provides a higher protection rate against all abnormal cytologies than does Gardasil [27% (95% confidence interval (CI), 21, 33) vs. 17% (95% CI, 10, 24)] and a higher reduction in excisional treatments for CIN 2/3 disease [70% (95% CI, 58, 79) vs. 42% (95% CI, 28, 54)]. The increased reduction in excisional therapies for CIN 2/3 exhibited by Cervarix is most likely because of the cross-protection it offers against other nonvaccine HPV types.
Clinical Reduction in Abnormal Cytology and Excisional Therapies by HPV Vaccines in HPV-naive Women Cervarix4
ASCUS LSIL HSIL All abnormal cytology Reduction in colposcopies Reduction in excisional therapies
Gardasil150
Efficacy (%)
95% CI
Efficacy (%)
95% CI
23 24 54 27 29 70
17, 39 14, 33 5, 79 21, 33 22, 36 58, 79
22 17 45 17 20 42
9, 36 9, 24 28, 54 10, 24 12, 27 28, 54
ASCUS indicates atypical squamous cells of undetermined significance; CI, confidence interval; LSIL, low grade squamous intraepithelial lesion; HSIL, high grade intraepithelial lesion; HPV, human papillomavirus.
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Primary Prevention for Cervical Cancer and HPV TABLE 3.
259
Cross-Protection Against Other Persistent HPV Infections Among HPV-naive Women by Vaccination
HPV 31 HPV 33 HPV 45 HPV 51 HPV 52 HPV 31/33/45/52/58
Cervarix Efficacy Compared to Control151
Gardasil Efficacy Compared to Control152
Gardasil+ 5 Efficacy Compared to Gardasil Recipients153
Efficacy (%)
95% CI
Efficacy (%)
95% CI
Efficacy (%)
95% CI
77 43 79 26 19
67, 84 19, 60 61, 89 12, 37 3, 32
46 29 8 — 6
15, 66 – 45, 66 – 67, 49 — – 54, 42 96
94, 97
CI indicates confidence interval; HPV, human papillomavirus.
Cross-protection against HPV types not covered by the VLP content of the Cervarix vaccine has been established in 2 ways: the first way measures the post hoc efficacy each vaccine provides to naive women by HPV type, and the second way calculates the magnitude of protection against histologic disease regardless of HPV associations, similar to that is seen in the reduction of excisional therapies. Table 3 presents the direct efficacy against non–vaccine-containing HPV types. Cervarix has substantial direct evidence of cross-protective efficacy against 5 oncogenic infections not included in its HPV VLP formulation, including HPV 45, which is one of the main contributors to adenocarcinoma. It is evident that Gardasil has minimal crossTABLE 4.
protection in its original formulation, but by adding 5 oncogenic VLPs, Gardasil+ 5 is able to show efficacy against these persistent infections. The maximal efficacy against CIN 2/3 by Gardasil+ 5 is estimated to be 75% to 85% on the basis of the original Gardasil studies.16 Efficacy is also measured by disease prevention regardless of HPV type. Table 4 presents the efficacy against histologic changes regardless of HPV causation. Cervarix shows 93% efficacy against CIN 3 caused by any HPV type, which is substantially higher than Gardasil alone at 43% or Gardasil+ 5 with an estimated maximal CIN 2/3 efficacy of 85%. Adenocarcinoma in situ did not occur very often in either the Cervarix or the Gardasil trials, but when caused by HPV 16/18,
HPV Vaccine Efficacy to Prevent Histologic CIN Changes Among Women Naive to HPV Cervarix4
CIN 2+ caused by HPV 16/18 only CIN 3+ caused by HPV 16/18 only AIS caused by HPV 16/18 only CIN 2+ caused by any HPV CIN 3+ caused by any HPV
Gardasil150
Efficacy (%)
95% CI
Efficacy (%)
95% CI
95 92 100 65 93
88, 98 67, 99 16, 100 53, 74 79, 99
100 100 60 43 43
91, 100 91, 100 NS 24, 57 13, 63
CIN 2+ means cervical intraepithelial neoplasia grade 2, grade 3, invasive squamous cervical cancer, adenocarcinoma in situ, and adenocarcinoma. CIN 3+ means cervical intraepithelial neoplasia grade 3, invasive squamous cervical cancer, adenocarcinoma in situ, and adenocarcinoma. AIS indicates adenocarcinoma in situ; CI, confidence interval; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.
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it was prevented by both vaccines, albeit with a greater efficacy by Cervarix.4 Other HPV types also appear to be cross-protected by Cervarix. Although Gardasil has VLPs to HPV 6 and 11, the cause of 90% of genital warts, Cervarix does not. Yet, during 3 years of exclusive Cervarix vaccination programs in the United Kingdom, the incidence of genital warts decreased by 21% in the observed population.17 Post hoc analysis of the Cervarix trial showed substantial and unexpected type-specific protection against persistent infections caused by genital wart-causing HPV types: HPV 6 (35%), HPV 11 (30%), and HPV 74 (50%).18
Age at Vaccination Age at vaccination is critically determined by the duration of vaccine efficacy and the peak incidence of HPV infection, which the vaccine is designed to prevent. After proving efficacy, duration, and affordability, the next challenge has been implementing the 3-dose HPV vaccine series in an adolescent population.19 The trials indicate that HPV vaccine efficacy will provide the greatest public health benefit in those with no prior exposure to HPV; yet, identifying this group is not easy. Unlike most childhood vaccines, current recommendations for HPV vaccination are to target 11- to 12-year-old girls, as there is less likelihood that they will have initiated sexual activity and hence will not be HPV exposed. Studies, however, show that 10% to 15% of the population is infected with oncogenic HPV genital or oral infections throughout childhood, and 2.5% have TABLE 5.
HPV 16/18 infection, which is the same proportion of infection as in the sexually active young adult US population.1,20–22 Other studies have shown that oncogenic genital HPV is present in the fingernail mucosa and on hands, and appears to be transmissible,23–25 making it entirely possible for a portion of the sexually naive target population to already be HPV DNA and/ or seropositive for oncogenic types. Age is not an accurate surrogate for HPV exposure.19 While targeting young HPV-naive females will result in the highest efficacy possible for a public health goal, vaccinating those who are older or with sexual experience may provide individual health benefits. Many studies have shown that
Primary Strategies for HPV Infection and Cervical Cancer Prevention DIANE M. HARPER, MD, MPH, MS,* and LESLIE R. DEMARS, MDw *Departments of Family and Geriatric Medicine, Obstetrics and Gynecology, Bioengineering, Epidemiology and Population Health, Health Promotion and Behavioral Sciences, University of Louisville School of Medicine, Louisville, Kentucky; and wDepartment of Obstetrics and Gynecology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
Abstract: Counseling messages for tobacco cessation, condom use, circumcision, and selective choice in the number of sexual partners can help reduce the risk of cervical cancer. Other sexual behavioral and reproductive risk factors for cervical cancer are a younger age at first intercourse and at first full-term pregnancy as well as increasing duration of combined hormonal oral contraceptive use. Micronutrients and supplements can reduce the risk of human papillomavirus infection, persistence, progression, and regression. Some human papillomavirus infections can be prevented by vaccination. Cervical cancer is best prevented by screening. Key words: HPV vaccines, efficacy, immune titers, dosing schedule
Prophylactic HPV Vaccines Human papillomavirus (HPV) is a double-stranded, about 8000-bp, DNA virus that has 2 late transcription regions and 7 early transcription regions as well as regulatory regions. The first late region, L1, produces a protein that represents the outermost coat of the virus. HPV vaccines contain replicates of the L1 protein called virus-like particles (VLPs) that are type specific (Table 1). In addition, each vaccine has its own adjuvant used to promote the durability of the immune response. There are 2 prophylactic HPV vaccines currently registered with national and international regulatory bodies: Cervarix and Gardasil/Silgard; in addition, Gardasil has added 5 additional oncogenic types against which it offered no original protection as a next-generation L1 VLP
Correspondence: Diane M. Harper, MD, MPH, MS, Departments of Family and Geriatric Medicine, Obstetrics and Gynecology, Bioengineering, Epidemiology and Population Health, Health Promotion and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY. E-mail: diane.m.harper@ gmail.com The authors declare that they have nothing to disclose. CLINICAL OBSTETRICS AND GYNECOLOGY
256 | www.clinicalobgyn.com
/
VOLUME 57
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NUMBER 2
/
JUNE 2014
Primary Prevention for Cervical Cancer and HPV TABLE 1.
Composition of 3 Prophylactic HPV Vaccines Cervarix34
HPV VLP protein content
Total L1 VLP protein content Adjuvant
257
Gardasil/Silgard35
Gardasil+ 516
HPV 16
20 mg
HPV 16
40 mg
HPV 16
60 mg
HPV 18
20 mg
HPV 18 HPV 6 HPV 11
20 mg 20 mg 40 mg
HPV 18 HPV 31 HPV 33 HPV 45 HPV 52 HPV 58 HPV 6 HPV 11
40 mg 20 mg 20 mg 20 mg 20 mg 20 mg 30 mg 40 mg 270 mg
225 mg Aluminum hydroxyphosphate sulfate
500 mg
40 mg
120 mg
3-O-desacyl-4-mono- 50 mg phosphoryl lipid A Aluminum hydroxide 500 mg Aluminum salt hydroxyphosphate sulfate
HPV indicates human papillomavirus; VLP, virus-like particle.
vaccine (Table 1). All vaccines have proven efficacy against type-specific HPV infections.1 None of the vaccines has proven efficacy against any HPV-associated cancer and will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.2 Unlike cervical cancer, there are no secondary screening tests universally acknowledged to detect HPV-associated precancers of the head and neck, penis, anus, vulva, or vagina.3 In the setting of effective cervical cytology screening programs, prophylactic HPV vaccines will prevent some abnormal cytologic changes as well as some cervical intraepithelial neoplasia grade 3 (CIN 3) diseases, thereby preventing the need for surgical treatment of the CIN 3 precancer. This review will provide specific data for the 2 approved prophylactic vaccines, and where data are available, the nonavalent ‘‘Gardasil+ 5’’ vaccine data for efficacy and immunogenicity. All efficacy studies to date show that prevention of type-specific HPV infections is most easily accomplished by type-specific vaccination before HPV infection. Both
Cervarix and Gardasil are effective in populations that have already been sexually active or exposed to HPV, but at a lesser efficacy compared with populations that are naive to the HPV types before vaccination.4,5 Gardasil efficacy in males is restricted to short follow-up times and more rapid loss of antibody titers than seen in females6; there are no efficacy studies of Cervarix in males.
The Focus on Cervical Cancer Prevention of cervical cancer has focused on the identification of cervical cancer precursors with cytologic screening and the treatment of high-grade precancerous lesions. With this model, the incidence of cervical cancer in the United States has decreased by 80% since the widespread adoption of Pap testing.7 There are 2 main histologic categories of cervical cancer: squamous cell and adenocarcinoma. The majority of the cancers are squamous, starting at the transformation zone of the cervix, detectable with cervical samplings at the time of Pap testing, www.clinicalobgyn.com
258
Harper and DeMars
and usually visible at colposcopy.8 Adenocarcinoma, in contrast, develops in the glandular cells of the endocervix, is harder to detect by cytology, harder to detect by colposcopy, presents at later stages, and is associated with a higher mortality.9 Because of the effectiveness of cytologic screening and treatment for squamous cell precursors, the proportion of adenocarcinoma and adenocarcinoma in situ cancers diagnosed is increasing. As with squamous cell cancers, the most common HPV types associated with adenocarcinoma include HPV 16, 18, and 45.10 Although Pap testing remains the best way to detect squamous cervical cancer precursors, a convincing argument for HPV vaccination would be the prevention of adenocarcinomas and their precursor lesion, adenocarcinoma in situ. This would elevate the HPV vaccine discussion above the economic evaluation of costeffectiveness within a screening program. Economic analyses have shown that US cervical cancer prevention and treatment accounts for 92% of the HPVrelated economic burden with 8% allocated to the costs for care and prevention of vulvar, vaginal, penile, anal, oropharyngeal, and mouth cancers as well as juvenile-onset recurrent respiratory papillomatosis and anogenital warts.11,12 Specific models of HPV vaccination strategies have consistently shown that the duration of vaccine protection is one of the most potent predictors of cancer TABLE 2.
reduction; no cancer prevention is possible if vaccination efficacy is not maintained for at least 15 years without waning.13–15 Although the incidence of noncervical diseases may eventually be reduced with vaccination, it is a small highlight economically compared with what needs to be done to prevent HPV cervical disease in the United States and globally.
Reduction in Cytologic Cervical Abnormalities and Surgical Treatments Both vaccines provide some level of efficacy against those HPV infections that persist to cause cytologic abnormalities and subsequent excisional therapies for high-grade precancerous lesions. Table 2 details the differences in these efficacies between Cervarix and Gardasil. In the HPV-naive population, Cervarix provides a higher protection rate against all abnormal cytologies than does Gardasil [27% (95% confidence interval (CI), 21, 33) vs. 17% (95% CI, 10, 24)] and a higher reduction in excisional treatments for CIN 2/3 disease [70% (95% CI, 58, 79) vs. 42% (95% CI, 28, 54)]. The increased reduction in excisional therapies for CIN 2/3 exhibited by Cervarix is most likely because of the cross-protection it offers against other nonvaccine HPV types.
Clinical Reduction in Abnormal Cytology and Excisional Therapies by HPV Vaccines in HPV-naive Women Cervarix4
ASCUS LSIL HSIL All abnormal cytology Reduction in colposcopies Reduction in excisional therapies
Gardasil150
Efficacy (%)
95% CI
Efficacy (%)
95% CI
23 24 54 27 29 70
17, 39 14, 33 5, 79 21, 33 22, 36 58, 79
22 17 45 17 20 42
9, 36 9, 24 28, 54 10, 24 12, 27 28, 54
ASCUS indicates atypical squamous cells of undetermined significance; CI, confidence interval; LSIL, low grade squamous intraepithelial lesion; HSIL, high grade intraepithelial lesion; HPV, human papillomavirus.
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Primary Prevention for Cervical Cancer and HPV TABLE 3.
259
Cross-Protection Against Other Persistent HPV Infections Among HPV-naive Women by Vaccination
HPV 31 HPV 33 HPV 45 HPV 51 HPV 52 HPV 31/33/45/52/58
Cervarix Efficacy Compared to Control151
Gardasil Efficacy Compared to Control152
Gardasil+ 5 Efficacy Compared to Gardasil Recipients153
Efficacy (%)
95% CI
Efficacy (%)
95% CI
Efficacy (%)
95% CI
77 43 79 26 19
67, 84 19, 60 61, 89 12, 37 3, 32
46 29 8 — 6
15, 66 – 45, 66 – 67, 49 — – 54, 42 96
94, 97
CI indicates confidence interval; HPV, human papillomavirus.
Cross-protection against HPV types not covered by the VLP content of the Cervarix vaccine has been established in 2 ways: the first way measures the post hoc efficacy each vaccine provides to naive women by HPV type, and the second way calculates the magnitude of protection against histologic disease regardless of HPV associations, similar to that is seen in the reduction of excisional therapies. Table 3 presents the direct efficacy against non–vaccine-containing HPV types. Cervarix has substantial direct evidence of cross-protective efficacy against 5 oncogenic infections not included in its HPV VLP formulation, including HPV 45, which is one of the main contributors to adenocarcinoma. It is evident that Gardasil has minimal crossTABLE 4.
protection in its original formulation, but by adding 5 oncogenic VLPs, Gardasil+ 5 is able to show efficacy against these persistent infections. The maximal efficacy against CIN 2/3 by Gardasil+ 5 is estimated to be 75% to 85% on the basis of the original Gardasil studies.16 Efficacy is also measured by disease prevention regardless of HPV type. Table 4 presents the efficacy against histologic changes regardless of HPV causation. Cervarix shows 93% efficacy against CIN 3 caused by any HPV type, which is substantially higher than Gardasil alone at 43% or Gardasil+ 5 with an estimated maximal CIN 2/3 efficacy of 85%. Adenocarcinoma in situ did not occur very often in either the Cervarix or the Gardasil trials, but when caused by HPV 16/18,
HPV Vaccine Efficacy to Prevent Histologic CIN Changes Among Women Naive to HPV Cervarix4
CIN 2+ caused by HPV 16/18 only CIN 3+ caused by HPV 16/18 only AIS caused by HPV 16/18 only CIN 2+ caused by any HPV CIN 3+ caused by any HPV
Gardasil150
Efficacy (%)
95% CI
Efficacy (%)
95% CI
95 92 100 65 93
88, 98 67, 99 16, 100 53, 74 79, 99
100 100 60 43 43
91, 100 91, 100 NS 24, 57 13, 63
CIN 2+ means cervical intraepithelial neoplasia grade 2, grade 3, invasive squamous cervical cancer, adenocarcinoma in situ, and adenocarcinoma. CIN 3+ means cervical intraepithelial neoplasia grade 3, invasive squamous cervical cancer, adenocarcinoma in situ, and adenocarcinoma. AIS indicates adenocarcinoma in situ; CI, confidence interval; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.
www.clinicalobgyn.com
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Harper and DeMars
it was prevented by both vaccines, albeit with a greater efficacy by Cervarix.4 Other HPV types also appear to be cross-protected by Cervarix. Although Gardasil has VLPs to HPV 6 and 11, the cause of 90% of genital warts, Cervarix does not. Yet, during 3 years of exclusive Cervarix vaccination programs in the United Kingdom, the incidence of genital warts decreased by 21% in the observed population.17 Post hoc analysis of the Cervarix trial showed substantial and unexpected type-specific protection against persistent infections caused by genital wart-causing HPV types: HPV 6 (35%), HPV 11 (30%), and HPV 74 (50%).18
Age at Vaccination Age at vaccination is critically determined by the duration of vaccine efficacy and the peak incidence of HPV infection, which the vaccine is designed to prevent. After proving efficacy, duration, and affordability, the next challenge has been implementing the 3-dose HPV vaccine series in an adolescent population.19 The trials indicate that HPV vaccine efficacy will provide the greatest public health benefit in those with no prior exposure to HPV; yet, identifying this group is not easy. Unlike most childhood vaccines, current recommendations for HPV vaccination are to target 11- to 12-year-old girls, as there is less likelihood that they will have initiated sexual activity and hence will not be HPV exposed. Studies, however, show that 10% to 15% of the population is infected with oncogenic HPV genital or oral infections throughout childhood, and 2.5% have TABLE 5.
HPV 16/18 infection, which is the same proportion of infection as in the sexually active young adult US population.1,20–22 Other studies have shown that oncogenic genital HPV is present in the fingernail mucosa and on hands, and appears to be transmissible,23–25 making it entirely possible for a portion of the sexually naive target population to already be HPV DNA and/ or seropositive for oncogenic types. Age is not an accurate surrogate for HPV exposure.19 While targeting young HPV-naive females will result in the highest efficacy possible for a public health goal, vaccinating those who are older or with sexual experience may provide individual health benefits. Many studies have shown that
