Fonc 14 1386167
Fonc 14 1386167
Fonc 14 1386167
REVIEWED BY
and Vicente Madrid-Marina 3
Kemin Li, Department of Oncology Gynecology, Instituto Nacional de Cancerologı´a (INCAN), México
1
Sichuan University, China City, Mexico, 2 Center for Population Health Research, Instituto Nacional de Salud Pública (INSP),
*CORRESPONDENCE
Cuernavaca, Mexico, 3 Chronic Infections and Cancer Division, Center for Research on Infectious
Aurelio Cruz-Valdez Diseases, Instituto Nacional de Salud Pública (INSP), Cuernavaca, Mexico
[email protected]
KEYWORDS
Within various vaccination programs, 47% predominantly doses in preventing high-grade disease. The findings revealed that
targeted girls at the age of 12 years. However, LMICs typically in a high-coverage setting, one dose of the vaccine demonstrated
targeted younger girls (9-10 years) compared to HICs, where the comparable effectiveness to two or three doses in preventing high-
targeted age group was 11-13 years. grade cervical lesions (23).
Most countries adopted a two-dose HPV vaccination schedule
with a 6-month interval between doses. However, many countries
reported using a 12-month interval between the first and second 3.1 Efficacy
dose. In 2019, 76% of programs employed a single-cohort approach,
where all girls in the targeted age group were vaccinated The human papillomavirus (HPV) vaccine has emerged as a
simultaneously. However, some programs transitioned from a crucial instrument in tackling the HPV-related health challenge.
multiple-cohort strategy, where girls were vaccinated in sequential Recent data on the vaccine’s efficacy, immunogenicity, and safety
age groups, to a single-cohort approach (15). parameters are extensively scrutinized to illuminate the underlying
In certain LMICs where HPV vaccines are accessible, the mechanisms contributing to its success.
immunization rates can vary markedly. Statistics indicate that Extensive studies have provided compelling evidence
76.7% of individuals have received at least one dose of the HPV supporting the effectiveness of human papillomavirus (HPV)
vaccine, 67.1% have received the second dose, and 31.1% have vaccines in preventing HPV infections and associated diseases.
received the third dose (16, 17). Although there is a gradual increase Drolet et al. conducted a comprehensive systematic review and
in HPV vaccine coverage globally, in Mexico, the national meta-analysis, incorporating data from a substantial population of
vaccination program aimed at girls has shown a significant 60 million individuals. Their findings revealed that over a 5–8-year
decrease in coverage during the COVID-19 pandemic. In 2021, follow-up period, there was a remarkable decrease in the prevalence
HPV vaccine coverage among women in Mexico reached only 1%, a of HPV 16 and 18 by 83% (RR 0.17, 95% CI 0.11–0.25) among girls
substantial decline attributed to the pandemic (15). aged 13-19 years who received the vaccine, and by 66% (RR 0.34,
95% CI 0.23–0.49) among women aged 20-24 years. Similarly, in
Australia, a study involving women aged 18-24 years demonstrated
3 Human papillomavirus vaccines a substantial reduction in HPV 6/11/16/18 infections by 86% after
completing the three-dose vaccination regimen and by 76% after
Three HPV vaccines are licensed for use: bivalent (Cervarix), receiving at least one dose, compared to unvaccinated counterparts.
quadrivalent (Gardasil), and nonavalent (Gardasil 9). These These findings underscore the profound impact of HPV vaccines in
vaccines prevent infection with HPV types 6/11/16/18/31/33/45/ protecting individuals from HPV-related health concerns (12).
52/58 (18). All three vaccines are based on non-infectious In countries exhibiting high uptake of the HPV vaccine, such as
recombinant type-specific L1 capsid proteins assembled into Australia and Denmark, substantial declines were observed in the
virus-like particles (VLPs) as immunogens (19). Humoral prevalence and incidence of genital warts. The youngest age groups
immunity against HPV is mediated by antibodies that recognize receiving vaccinations demonstrated the most significant
the L1 and L2 capsid proteins. B cells are activated by HPV antigens reductions, with a 67% relative risk (RR) decrease (RR 0·33, 95%
presented on MHC class II molecules by dendritic cells. A specific CI 0·24–0·46) among girls aged 15–19 years and a 54% RR decrease
TH2-cell receptor recognizes the MHC-II/L1-L2 antigen complex. (RR 0·46, 95% CI 0.36–0.60) among women aged 20–24 years.
Activated B cells differentiate into memory and plasma B cells, Furthermore, the efficacy of the vaccination was highlighted by a
producing HPV-specific antibodies (20). 51% decrease in cervical intraepithelial neoplasia grade 2 or worse
Licensed HPV vaccines have undergone comprehensive safety, (CIN2+) after 5–9 years among screened girls aged 15–19 years (RR
immunogenicity, and efficacy evaluations among young females 0·49, 95% CI 0·42–0·58) and a 31% decrease among women aged
aged 15-26. Consequently, organizations such as the World Health 20–24 years (RR 0·69, 95% CI 0·57–0·84) (24). Similar positive
Organization (WHO) advocate the inclusion of the HPV vaccine in outcomes were reported with the nonavalent HPV vaccine, which
routine immunization schedules, with recommendations for girls demonstrated an approximate 97% efficacy in preventing high-
starting as early as age 9. The vaccination regimen consists of a two- grade cervical, vulvar, and vaginal lesions due to additional HPV
dose schedule for individuals receiving the initial dose before their types (31, 33, 45, 52, 58). These findings strongly support the
15th birthday, with an interval between doses ranging from 6 to 12 effectiveness of HPV vaccination in reducing the burden of HPV-
months. Alternatively, a three-dose schedule is recommended for associated diseases (25).
individuals initiating vaccination at 15 or older and for The HPV vaccine has proven effective in preventing HPV
immunocompromised individuals. This three-dose schedule infection, genital warts, and high-grade cervical lesions (CIN2+
involves administering the first dose and the second and third and CIN3+) (26). Additionally, it reduces the risk of invasive
doses at 1-2 months and six months, respectively (21, 22). cervical cancer. A study by Lei et al. showed an 88% lower risk of
In a post-hoc trial analysis, the effectiveness of the quadrivalent cervical cancer among individuals vaccinated before 17 years of age
HPV vaccine was evaluated against cervical intraepithelial neoplasia (27). However, an Australian Vaccination Program report revealed
(CIN) 2 or 3, adenocarcinoma in situ (AIS), and cancer. The that while cumulative HPV vaccination coverage increased from
analysis was conducted over seven years following vaccination, January 1, 2007, to December 31, 2019, the incidence rate of cervical
and the effectiveness of one dose was compared to two or three cancer remained comparable between the post-vaccination and pre-
vaccination periods. Notably, the mortality rate decreased by against HPV types 31 and 45, although preliminary data indicated
12% (28). that this cross-protection may be short-lived (35). Notably, the
HPV vaccination has a substantial impact on preventing HPV- cross-protection antibody/immune response observed among
related diseases, notably cervical cancer. Determining the vaccine’s participants who had received all three doses of the bivalent or
long-term effectiveness in lowering the overall incidence of cervical quadrivalent vaccine is not directly comparable to the specific
cancer requires further investigation. Research also focuses on the reactions elicited by the HPV vaccine types (35).
vaccine’s efficacy based on the number of doses administered.
Prelicensure vaccines demonstrated high efficacy with three-dose
schedules. Studies investigating the noninferiority of two doses 3.4 Vaccine safety
given at six or 12-month intervals revealed that ≥97.9% of
individuals aged 9–14 years seroconverted to all nine HPV types, The safety of vaccines is of paramount importance in public
with a higher conversion rate observed in this age group when health. Vaccines undergo rigorous safety evaluations to ensure their
receiving two doses. Some studies have reported comparable widespread use is justified. The HPV vaccine has been extensively
effectiveness with three, two, and one doses (29), indicating the studied, and its safety profile has been well-established. Large-scale
potential for fewer doses in the future. clinical trials have demonstrated the safety of HPV vaccines. These
trials have compared the safety profiles of HPV vaccines to those of
other vaccines and found them comparable. Common adverse
3.2 Immunogenicity events associated with HPV vaccines are generally mild and
include pain at the injection site and mild fever (36). The risk of
Immunogenicity, a crucial factor influencing the effectiveness of serious adverse events is extremely low. After extensive analysis of
vaccines, has been consistently demonstrated in HPV vaccines. the effectiveness, immunogenicity, and safety of HPV vaccination,
These vaccines elicit robust and sustained immune responses, the recommendations are highly compelling (Table 1).
surpassing the immunity achieved through natural infection (30,
31). Seroconversion, defined as developing specific antibodies
against the viral antigen, was observed in nearly 100% of 4 Future directions
individuals vaccinated with the 3-dose series. The titer of these
antibodies increased after each dose and gradually declined over Preventive medicine is undergoing significant transformation
time following the completion of the vaccination course. Peak due to the ongoing advancements in HPV vaccine technology.
antibody titers induced by HPV vaccines are significantly higher Researchers are actively optimizing vaccination schedules to ensure
than those generated after natural infection (32, 33). maximum efficacy and long-term protection. They are also
Immunological memory elicited by HPV vaccines results in
persistent antibody titers, providing long-term protection. Studies
TABLE 1 Types of prophylactic HPV vaccines in Mexico and
have demonstrated the stability of antibody levels over 9.4 years
recommendations through the years.
post-vaccination. This enduring immunity is attributed to the
induction of memory B cells, which play a crucial role in Year Recommendations HPV
maintaining immunological memory (34). Titers exhibit an Vaccines
inverse relationship with age, with higher titers observed in 2009 Routine vaccination of a single birth cohort of girls Bivalent
individuals aged 9-26 years compared to older age groups (24). aged 9–13 y with a 3-dose schedule Qudrivalent
Longitudinal evaluations of immune responses up to 24 months
2014 2-dose schedule, if starting series at age 9–14 y; 3- Bivalente
post-vaccination revealed a significant increase in geometric dose schedule for older girls/women or for Quadrivalent
antibody titers (GMTs) for HPV type 16 (2.4-5.8-fold) and HPV immunocompromised persons
type 18 (7.7-9.4-fold). These findings underscore the robust and 2017 Vaccination of multiple cohorts of girls aged 9–14 y Bivalent
sustained immunological response induced by HPV vaccines. when vaccine first introduced; vaccination of other Qudrivalent
populations (females aged ≥15 y or males), only if
feasible, affordable, cost-effective, and not diverting
resources from primary target population or from
3.3 Cross-protection cervical cancer screening programs
exploring strategies to expand genotype coverage, aiming to develop making it easier for girls to get vaccinated. Regarding increasing
vaccines that protect against a broader range of HPV strains. vaccination rates among girls in Mexico, balancing individual rights,
Furthermore, efforts are being made to address barriers to vaccine public health priorities, and social justice considerations is necessary.
access, particularly in resource-limited settings, to ensure equitable It’s recommended that the agencies involved coordinate their
distribution and utilization of these life-saving vaccines (37). efforts to ensure fair and equal access to HPV vaccination. Any
further delays in increasing coverage of the target population could
lead to continued loss of life from preventable diseases and could
5 Vaccines in the also pose a significant financial burden on the health system.
secondary prevention
In secondary prevention strategies for CC, adjuvant HPV Author contributions
vaccination after treatment for CIN has been investigated. Several
studies have evaluated the efficacy of this approach in reducing the JG: Writing – original draft, Writing – review & editing. AC:
risk of recurrence. Results consistently indicate a lower incidence of Writing – original draft, Writing – review & editing. VM: Writing –
recurrent CIN 1, CIN 2+, and CIN3 in vaccinated groups compared original draft, Writing – review & editing.
to unvaccinated groups, with statistically significant p-values (p <
0.0001) (38).
Moreover, adjuvant HPV vaccination has demonstrated Funding
effectiveness in reducing the risk of anal intraepithelial neoplasia
(p = 0.005) and recurrent respiratory papillomatosis. However, no The author(s) declare that no financial support was received for
significant differences were observed in recurrence rates for the research, authorship, and/or publication of this article.
anogenital warts and vulvar intraepithelial neoplasia (39, 40).
Further research is necessary to elucidate the precise role of HPV
vaccination as an adjuvant therapy following primary treatment. Acknowledgments
We are grateful to Oscar Medina-Contreras, Lucely Cetina-
6 Conclusion Pé rez for their support in the design and editing.
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