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  • Dr Jonathan Gui

Human Papilloma Virus (HPV) clinical study

Can I take the HPV vaccine despite being above 26 years old?

As you may have read that HPV is not recommended to people over the age of 26 years old. Should you still get the vaccine?

The plain answer is yes! HPV Gardasil 9 is used to prevent HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 and studies have shown that people above the age of 26 years old may not benefit as much as below the age of 26 years old.


There is a logic behind this study.

1. Study design on males and females from the age of 9 to 15 years old (GARDASIL-4):

  1. SIMPLIFIED VERSION Girls and boys without prior exposure to sex were included in this study. They were given GARDASIL-4 and after 8.5 years follow up, there were no reported cases of HPV 6-, 11-, 16-, or 18-related CIN (any grade), AIS, VIN, VaIN, cervical cancer, vulvar cancer, vaginal cancer, or external genital lesions were observed.

  2. COMPREHENSIVE VERSION An extension study of 614 girls and 565 boys 9 through 15 years of age at enrollment who were randomized to vaccination with GARDASIL actively followed subjects for endpoint cases of HPV 6-, 11-,16-, or 18-related persistent infection, CIN (any grade), AIS, VIN, VaIN, cervical cancer, vulvar cancer, vaginal cancer, and external genital lesions from the initiation of sexual activity or age 16 onwards. An interim analysis of the per-protocol effectiveness population included 246 girls and 168 boys who completed the GARDASIL vaccination series within one year, were seronegative to the relevant HPV type at the initiation of the vaccination series and had not initiated sexual activity prior to receiving the third dose of GARDASIL. The median follow-up from the first dose of vaccine was 7.2 years with a range of 0.5 to 8.5 years. At the time of interim analysis, no cases of persistent infection of at least 12 months’ duration and no cases of HPV 6-, 11-, 16-, or 18-related CIN (any grade), AIS, VIN, VaIN, cervical cancer, vulvar cancer, vaginal cancer, or external genital lesions were observed over a total 1,105 person-years at risk. There were 4 cases of HPV 6-, 11-, 16-, or 18-related persistent infection of at least 6 months’ duration, including 3 cases related to HPV 16 and 1 case related to HPV 6, none of which persisted to 12 months’ duration.

  3. CONCLUSION GARDASIL-4 should be started before being sexually active. Children who receive GARDASIL-4 before sexual maturity gain about almost 100% efficacy against HPV infection.


2. Study design on males and females from the age of 16 to 25 years old (GARDASIL-4):

  1. SIMPLIFIED VERSION

  2. Study Design on girls and women from 16 to 26 years old of age: Efficacy of GARDASIL 4 in 1 was assessed in double-blind, randomized clinical studies evaluated 24,596 individuals (20,541 girls and women 16 to 26 years of age and 4,055 boys and men 16 to 26 years of age at enrollment). The group of girls and women were further divided into a group vaccinated with Gardasil-4 and another group as a control group (not receiving Gardasil-4). After comparing the vaccinated group versus the control group, it was concluded that the vaccinated group had fewer cases of cervical cancer, anal cancer, and genital wart cases as compared to the control group (not receiving Gardasil-4). Whereas the vaccinated group of girls and women had “Zero” case of Vulvar and Vaginal Cancer.

  3. Study Design on boys and men from 16 to 26 years old of age: The group of boys and men were further divided into a group vaccinated with Gardasil-4 and another group as a control group (not receiving Gardasil-4). After comparing the vaccinated group versus the control group, it was concluded that the vaccinated group had less cases of condyloma, anal cancer, and genital wart cases as compared to the control group (not receiving Gardasil-4). Whereas the vaccinated group of boys and men had “Zero” case of Prostatic Cancer. Efficacy was evaluated in subjects who received all 3 vaccinations within 1 year of enrollment, had the following results of prevention:

  4. COMPREHENSIVE VERSION

  5. Study Design on girls and women from 16 to 26 years old of age: Efficacy of GARDASIL was assessed in five AAHS-controlled, double-blind, randomized clinical trials evaluating 24,596 individuals 16 through 26 years of age (20,541 girls and women and 4,055 boys and men). The results of these trials are shown in Table 6 below. In an extension study in females, 16 through 26 years of age at enrollment, prophylactic efficacy of GARDASIL through Month 60 against overall cervical and genital disease related to HPV 6, 11, 16, and 18 was 100% (95% CI: 12.3%, 100%) compared to AAHS control. An extension study in girls and women 16 through 23 years of age used national healthcare registries in Denmark, Iceland, Norway, and Sweden to monitor endpoint cases of HPV 6-, 11-, 16-, or 18-related CIN (any grade), AIS, cervical cancer, vulvar cancer, or vaginal cancer among 2,650 girls and women 16 through 23 years of age at enrollment who were randomized to vaccination with GARDASIL. An interim analysis of the per-protocol effectiveness population included 1,902 subjects who completed the GARDASIL vaccination series within one year were naïve to the relevant HPV type through 1-month post-dose 3, had no protocol violations, and had follow-up data available. The median follow-up from the first dose of vaccine was 6.7 years with a range of 2.8 to 8.4 years. At the time of interim analysis, no cases of HPV 6-, 11-, 16-, or 18-related CIN (any grade), AIS, cervical cancer, vulvar cancer, or vaginal cancer were observed over a total of 5,765 person-years at risk.

  6. Study Design on boys and men from 16 to 26 years old of age: A study conducted in boys and men in individuals aged 16 to 26 years old (4055 boys and men) were divided equally into those received GARDASIL-4 and AAHS control. The population consisted of individuals who received all three vaccinations within one year of enrollment, did not have major deviations from the study protocol, were naïve (PCR negative and seronegative) to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1 and who remained PCR negative to the relevant HPV type(s) through one month post-dose 3 (Month 7).In boys and men who had external genital lesions related to HPV HPV 6-, 11-, 16-, or 18 showed in the GARDASIL group had 90.6% efficacy as compared to AAHS control group. Condyloma related to HPV HPV 6-, 11-, 16-, or 18 showed in the GARDASIL group had 90.6% efficacy as compared to AAHS control group. Finally, Prostate intraepithelial neoplasia (PIN 1/2/3) related to HPV HPV 6-, 11-, 16-, or 18 showed in the GARDASIL group had 100% efficacy as compared to AAHS control group. An additional study was conducted to show the efficacy endpoint of GARDASIL against AIN 1/2/3 (77.5% efficacy), AIN 2/3 (74.9% efficacy), AIN 1 (73% efficacy), condyloma acuminatum (100% efficacy) and non-acuminate lesion (60.4% efficacy) compared against AAHS control group.

  7. CONCLUSION: The vaccinated group had a lesser incidence of Cervical cancer, Anal cancer, Genital wart, and “ZERO” cases of Vulvar and Vaginal Cancer, Penile cancer. Get all boys and girls from age 16 to 26 years old vaccinated with GARDASIL-4.


3. Study design on males and females from the age of 27 to 45 years old (GARDASIL-4):

  1. SIMPLIFIED VERSION

  2. Study Design on girls and women from 27 to 45 years old of age: 3253 women were divided into 2 groups equally to look at the efficacy of GARDASIL-4 in PERSISTENT HPV 6-, 11-, 16- or 18 infection-related with the genital wart, vulvar, vaginal dysplasia of any grade, cervical intraepithelial neoplasm grade 1/2/3, adenocarcinoma in situ, and cervical cancer. The first group received GARDASIL-4 and the second group was the AAHS control group (not receiving GARDASIL-4). The population receiving GARDASIL-4 had 87.7% efficacy against PERSISTENT HPV 6-, 11-, 16- or 18 infection-related with the genital wart, vulvar, vaginal dysplasia of any grade, cervical intraepithelial neoplasm, adenocarcinoma in situ, and cervical cancer. A more specific targeted population receiving GARDASIL-4 had 95% efficacy against PERSISTENT HPV 6-, 11-, 16- or 18 infection-related with the genital wart, cervical dysplasia of any grade, and cervical intraepithelial neoplasm grade 1. Another extension of the study was conducted in 600 subjects who had PERSISTENT HPV 6-, 11-, 16- or 18 infection-related with the genital wart, cervical dysplasia of any grade, and cervical intraepithelial neoplasm grade 1 and they received GARDASIL-4. They were followed-up about 8.9 years from the last HPV dose and the results showed that there were no cases of genital wart, cervical dysplasia of any grade, and cervical intraepithelial neoplasm. Then the study also showed that were NO SIGNIFICANT efficacy with PERSISTENT HPV 16- or 18 infection-related to cervical intraepithelial neoplasm grade 2/3, adenocarcinoma in situ, and cervical cancer.

  3. Study Design on boys and men from 27 to 45 years old of age: This particular study is limited to boys and men as the emphasis of GARDASIL-4 was studied more in women. Looking at GARDASIL-4 usage in PERSISTENT warts related to HPV 6 and 11, has been shown to give efficacy in women about 95%. So we can assume that GARDASIL-4 will be equally effective for boys and men. However, there are limited data to support GARDASIL-4 for other PERSISTENT 16- or 18 infection-related with adenocarcinoma in situ when they received GARDASIL-4. If we look at the study conducted in girls and women from 27 to 45 years old of age, GARDASIL-4 still can be effective in cervical dysplasia, therefore, it is also possible that GARDASIL-4 can also be effective in anal dysplasia for men.

  4. COMPREHENSIVE 

  5. Study Design on girls and women from 27 to 45 years old of age: A clinical trial evaluated the efficacy of GARDASIL in 3,253 women 27 through 45 years of age, based on a combined endpoint of HPV 6-, 11-, 16- or 18-related persistent infection, genital warts, vulvar and vaginal dysplastic lesions of any grade, CIN of any grade, AIS, and cervical cancer. These women were randomized 1:1 to receive either GARDASIL or AAHS control. The clinical trial was conducted in two phases: a base study and a long-term study extension. The per-protocol efficacy (PPE) population received all three vaccinations within one year of enrollment, did not have major deviations from the study protocol, were naïve (PCR negative and seronegative) to the relevant HPV type(s) (Types 6, 11, 16 and 18) prior to dose 1 and remained PCR negative to the relevant HPV type(s) through one month post-dose 3 (Month 7).In the base study (median duration of follow-up of 3.5 years post-dose 3), the efficacy of GARDASIL against the combined incidence of HPV 6-, 11-, 16-, and 18-related persistent infection, genital warts, VIN, VaIN, vulvar cancer, vaginal cancer, cervical dysplasia (any grade CIN), AIS and cervical cancer in the PPE population was 87.7% (95% CI: 75.4%, 94.6%). The efficacy estimate for the combined endpoint was driven primarily by the prevention of persistent infection. The efficacy of GARDASIL against the combined incidence of HPV 6-, 11-, 16-, and 18-related genital warts or cervical dysplasia was 95.0% (95% CI: 68.7%, 99.9%) in the PPE population. While no statistically significant efficacy was demonstrated for GARDASIL in the base study for prevention of cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), adenocarcinoma in situ (AIS) or cervical cancer related to HPV types 16 and 18, there was 1 case of CIN 2/3 observed in the GARDASIL group and 5 cases in the placebo group. The CIN 2 case in the GARDASIL group tested positive by PCR for HPV 16 and HPV 51. In the long-term extension of this study, subjects from Colombia (n=600) randomized to the GARDASIL group in the base study were monitored for HPV 6-, 11-, 16-, and 18-related genital warts or cervical dysplasia. The median follow-up post-dose 3 was 8.9 years with a range of 0.1 to 10.1 years over a total of 3,518 person-years. During the long-term extension phase, no cases of HPV 6-, 11-, 16-, or 18- related CIN (any grade) or genital warts were observed in the PPE population.

  6. Study Design on boys and men from 27 to 45 years old of age: Effectiveness of GARDASIL in men 27 through 45 years of age is inferred from efficacy data in women 27 through 45 years of age as described above and supported by immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of GARDASIL (0, 2, 6 months). A cross-study analysis of per-protocol immunogenicity populations compared Month 7 anti-HPV 6, 11, 16, and 18 GMTs of these 27- through 45-year-old men (Study A) to those of 16- through 26-year old boys and men (Study B) in whom efficacy of GARDASIL had been established (see Table 6). GMT ratios (Study A/Study B) for HPV 6, 11, 16, and 18 were 0.82 (95%CI: 0.65, 1.03), 0.79 (95%CI: 0.66, 0.93), 0.91 (95%CI: 0.72, 1.13), and 0.74 (95%CI: 0.59, 0.92), respectively. In a clinical trial, 150 men, 27 through 45 years of age, received a 3-dose regimen of GARDASIL (0, 2, 6 months). A cross-study analysis of per-protocol immunogenicity populations compared Month 7 anti-HPV 6, 11, 16, and 18 GMTs of these 27- through 45-year-old men (Study A) to those of 16- through 26-year old boys and men (Study B) in whom efficacy of GARDASIL had been established. GMT ratios (Study A/Study B) for HPV 6, 11, 16, and 18 were 0.82 (95%CI: 0.65, 1.03), 0.79 (95%CI: 0.66, 0.93), 0.91 (95%CI: 0.72, 1.13), and 0.74 (95%CI: 0.59, 0.92), respectively

  7. CONCLUSION: Both men and women 27 to 45 years old will gain lesser benefit from GARDASIL-4  as compared to people below 27 years old, nevertheless, those above 27 years old can still gain some benefit from GARDASIL-4 rather than not getting any benefit at all without GARDASIL-4.

Based on the safety profile established HPV vaccine can be started as early as 9 years old. Adults men and women should be vaccinated even if they are above the age of 26 years old in men.




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