TYPE Mini Review

PUBLISHED 23 April 2024

DOI 10.3389/fonc.2024.1386167

Cervical cancer prevention by

OPEN ACCESS vaccination: review
EDITED BY
Oscar Medina-Contreras, Julio Cesar González-Rodrı́guez 1, Aurelio Cruz-Valdez 2*
Mexico Children’s Hospital, Mexico

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]

RECEIVED 14 February 2024

ACCEPTED 03 April 2024 Abstract: Routine use of human papillomavirus (HPV) vaccines is recommended
PUBLISHED 23 April 2024 in adolescents under 15 years of age worldwide. Still, effective programs remain
CITATION suboptimal for several factors, making the WHO strategy to eradicate cervical
González-Rodrı´guez JC, Cruz-Valdez A and cancer public health with an uncertain future.
Madrid-Marina V (2024) Cervical cancer
prevention by vaccination: review.
Front. Oncol. 14:1386167. Objective: To review the literature on the effectiveness, long-term protection,
doi: 10.3389/fonc.2024.1386167 and safety of HPV vaccination programs and vaccination as adjuvant
COPYRIGHT management. This review aims to describe the current state of vaccination
© 2024 González-Rodrı´guez, Cruz-Valdez and
Madrid-Marina. This is an open-access article
programs and demonstrate the long-term protection and safety of vaccines
distributed under the terms of the Creative implemented worldwide targeting adolescent girls, with the most recent
Commons Attribution License (CC BY). The published evidence of the three prophylactic HPV vaccines – bivalent (bHPV),
use, distribution or reproduction in other
forums is permitted, provided the original quadrivalent (qHPV), and nonavalent (nHPV)-. We mainly focus on publications
author(s) and the copyright owner(s) are evaluating efficacy, dosing schemes, and HPV vaccination, as well as studies
credited and that the original publication in
contributing to the mounting evidence for the real-life effectiveness of
this journal is cited, in accordance with
accepted academic practice. No use, prophylactic HPV vaccines from several countries.
distribution or reproduction is permitted
which does not comply with these terms.
Findings: Human Papillomavirus vaccination programs have made remarkable
strides in preventing HPV-related diseases; countries with robust vaccination
efforts have witnessed substantial reductions in HPV-related diseases with a
decline in high-grade cervical abnormalities and genital warts (54%-83%).
However, global coverage remains uneven, with disparities between high-
income (HICs) and low-income countries (LMICs). The long-term efficacy of
the available human papillomavirus (HPV) goes up to 9.4 years and continues to
be immunogenic and well tolerated with an excellent safety profile.

Conclusions and relevance: As these are crucial topics in HPV vaccination, it is

essential to establish systems for continued monitoring of vaccine
immunogenicity, efficacy, and safety over time.

KEYWORDS

human papillomaviruses, HPV, Prophylactic HPV vaccines, effectiveness, HPV Vaccines

Frontiers in Oncology 01 frontiersin.org

González-Rodrı́guez et al. 10.3389/fonc.2024.1386167

1 Introduction In Mexico, CC prevention and control are guided by the official

standard NOM-014-SSA2-1994, endorsed by the national
Cervical cancer (CC) poses a significant public health issue. To government. This standard encompasses prevention, early
combat this problem, routine vaccination against human detection, diagnosis, treatment, control, and epidemiological
papillomavirus (HPV) is strongly encouraged globally for surveillance of CC. The program for early CC detection includes
adolescents younger than 15. However, the effectiveness of these a Papanicolaou smear test, complemented by biomolecular tests for
programs is often compromised by various factors. human papillomavirus (HPV) detection as an auxiliary tool to
To address this, a systematic literature review was conducted cervical cytology. Acetic acid-based direct visualization is also
using the PubMed database, focusing on research articles published employed when the Papanicolaou smear is unavailable. These
between January 2020 and April 2023. The search strategy involved screening tests are recommended for all asymptomatic women
combining the term “cervical cancer” with “prevention” and aged 25-64. However, women under 25 or over 64 years of age
“vaccination.” Priority was given to controlled, randomized with decreased morbidity and specific risk factors associated with
studies and systematic reviews with meta-analysis. However, all CC should also undergo testing (9).
available evidence was considered when sufficient studies The CC Action Program was initiated to decrease cervical cancer
were unavailable. mortality rates in Mexican females. To achieve this objective, various
strategic actions have been taken, encompassing collaboration,
fostering inter-sectoral and intra-sectoral coordination to streamline
1.1 Importance of HPV detection for efforts and resources; early detection, enhancing timely identification
cervical cancer prevention and screening for cervical cancer, ensuring prompt diagnosis and
treatment; quality control, implementing rigorous quality control
Cervical cancer is the fourth most common cancer in women measures to provide accurate and reliable diagnosis and treatment;
worldwide, with a projected 604,000 new cases and 342,000 deaths supervision and evaluation, establishing adequate supervision and
in 185 countries by 2020 (1). Furthermore, data obtained from the evaluation mechanisms to monitor program implementation, assess
Mexican Burden of Disease Study (MBD-2013) demonstrated that outcomes, and drive continuous improvement; research and
there were 102,241 cases of cancer in women, with CC being the development, promoting research and innovation to advance
second most common type of cancer after breast cancer. The age- understanding of cervical cancer, develop more effective prevention
standardized incidence rate for CC was 12 per 100,000, resulting in and treatment strategies, and evaluate program effectiveness; and
12,562 new cases. A ranking of age-standardized mortality rates infrastructure strengthening, investing in infrastructure and resources
among Mexican women showed that CC was the leading cause of to support the program, including adequate healthcare facilities,
death in states with higher levels of marginalization. These findings equipment, and trained personnel (7, 8, 10).
highlight the significant burden of CC in Mexico, particularly in
marginalized communities, underscoring the need for targeted
interventions to address this public health issue (2). 2 Current status of
The global prevalence of HPV infection among women without vaccination programs
cervical abnormalities ranges between 11 and 12%, with notable
variations across regions. Sub-Saharan Africa (24%), Eastern HPV vaccination programs have made remarkable strides in
Europe (21%), and Latin America (16%) exhibit the highest rates preventing HPV-related diseases, particularly cervical cancer (1,
(3). Age-stratified HPV distribution patterns reveal a peak among 11). Implementing widespread vaccination programs has led to
younger individuals (<25 years) and a resurgence in older age notable reductions in the prevalence of diseases associated with
groups (>45 years), specifically in the Americas and Africa. The human papillomavirus (HPV), including a decline in severe cervical
most commonly detected HPV genotypes are HPV-16 (3.2%), abnormalities and genital warts (12, 13). Despite these positive
HPV-18 (1.4%), HPV-52 (0.9%), HPV-31 (0.8%), and HPV-58 outcomes, disparities exist in global vaccination coverage, with
(0.7%) (4). The prevalence of oncogenic HPV genotypes is directly substantial differences between high-income countries (HICs) and
correlated with the severity of cervical lesions and the burden of low-income countries (LMICs). Low-resource settings often
HPV infection, highlighting the association between these encounter challenges in vaccine accessibility, distribution
genotypes and the progression to cancer (5). This link is further infrastructure, and effective health education, hindering the
supported by the observation that cervical cancer is predominantly equitable implementation of HPV vaccination programs.
caused by the high-risk HPV genotypes, particularly HPV-16 and In 2007, the United States, Canada, and Australia became the
HPV-18 (6). A study conducted in Mexico on a population of first countries to incorporate HPV vaccines into their national
60,135 women found that 24.78% of them had high-risk human immunization programs (NIPs). As of April 2022, 120 countries
papillomavirus (HR HPV). Among the HR HPV types, the most had introduced prophylactic HPV vaccines into their NIPs. Despite
prevalent were HPV-16 (4.13%), HPV-31 (4.12%), and HPV-51 this progress, only an estimated 13% of young girls globally are fully
(3.39%). On the other hand, HPV-18 (1.70%) was less common vaccinated, and HPV vaccines have yet to reach the populations
among the infected women (7, 8). most in need (14).

Frontiers in Oncology 02 frontiersin.org

González-Rodrı́guez et al. 10.3389/fonc.2024.1386167

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-

Frontiers in Oncology 03 frontiersin.org

González-Rodrı́guez et al. 10.3389/fonc.2024.1386167

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

2019 Owing to the global vaccine supply/demand Bivalent

Cross-protection against HPV types not targeted by the imbalance, target girls aged 13 or 14 y, before they Qudrivalent
vaccines was investigated in both prelicensure clinical trials and age out of the recommended primary target
population, or schedule an extended interval of 3–5 y
post-licensure evaluations. Data obtained from randomized trials
between the 2 doses, with dose 1 given to girls aged 9
and observational studies focused on cross-protection among fully or 10 y
vaccinated groups revealed a statistically significant cross-protective
2022 A one or two-dose schedule for girls aged 9-14 years Bivalent
efficacy with the bivalent vaccine, albeit with broad confidence A one or two-dose schedule for girls and women aged Qudrivalent
intervals, against HPV types 6 and 11 at six- and twelve-months 15-20 years 9-valent
post-vaccination, with the most pronounced effect observed for Two doses with a 6-month interval for women older HPV
than 21 years vaccine
HPV type 31. In the case of Gardasil, cross-protection was evident

Frontiers in Oncology 04 frontiersin.org

González-Rodrı́guez et al. 10.3389/fonc.2024.1386167

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.

The review results provide compelling evidence of the

significant impact of vaccination programs on HPV infection, Conflict of interest
anogenital warts, and high-grade cervical intraepithelial neoplasia,
as well as a considerable proportion of other HPV-related cancers, The authors declare that the research was conducted in the
such as oropharyngeal, vulva, vagina, and penis. Unfortunately, the absence of any commercial or financial relationships that could be
coverage of vaccination programs in 2021 has been affected due to construed as a potential conflict of interest.
the COVID-19 pandemic, particularly in countries like Mexico.
This situation has worsened the existing barriers and jeopardized
the progress achieved in primary prevention. Therefore, it is crucial Publisher’s note
to address these challenges on programmatic, logistical, and
financial fronts to continue the fight against HPV-related diseases. All claims expressed in this article are solely those of the authors
To ensure that everyone has access to vaccines, support programs and do not necessarily represent those of their affiliated
specifically tailored for marginalized populations must be created. organizations, or those of the publisher, the editors and the
Equitable access is critical in the case of HPV vaccines, as they play a reviewers. Any product that may be evaluated in this article, or
crucial role in reducing health disparities. Improving strategies for claim that may be made by its manufacturer, is not guaranteed or
increasing vaccination rates in underserved areas is essential to endorsed by the publisher.

References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global 4. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, De Sanjosé S. Cervical
cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 human papillomavirus prevalence in 5 continents: Meta-analysis of 1 million women
cancers in 185 countries. CA Cancer J Clin. (2021) 71:209–49. doi: 10.3322/caac.21660 with normal cytological findings. J Infect Dis. (2010) 202:1789–99. doi: 10.1086/657321
2. Gó mez-Danté s H, Lamadrid-Figueroa H, Cahuana-Hurtado L, Silverman-Retana 5. Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden
O, Montero P, Gonzá lez-Robledo MC, et al. The burden of cancer in Mexico, 1990- of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Heal.
2013. Salud Publica Mex. (2016) 58:118–31. doi: 10.21149/spm.v58i2.7780 (2016) 4:e609–16. doi: 10.1016/S2214-109X(16)30143-7
3. Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, 6. Murillo R, Herrero R, Sierra M, Forman D. Cervical cancer in Central and South
et al. Global burden of human papillomavirus and related diseases. Vaccine. (2012) 30: America: Burden of disease and status of disease control $. Cancer Epidemiol. (2016) 44:
F12–23. doi: 10.1016/j.vaccine.2012.07.055 S121–30. doi: 10.1016/j.canep.2016.07.015

Frontiers in Oncology 05 frontiersin.org

González-Rodrı́guez et al. 10.3389/fonc.2024.1386167

7. Torres-Poveda K, Ruiz-Fraga I, Madrid-Marina V, Chavez M, Richardson V. High vaccination programmes: updated systematic review and meta-analysis. Lancet. (2019)
risk HPV infection prevalence and associated cofactors: A population-based study in 394(10197):497–509. doi: 10.1016/s0140-6736(19)30298-3
female ISSSTE beneficiaries attending the HPV screening and early detection of cervical 25. Joura EA, Giuliano AR, Iversen O-E, Bouchard C, Mao C, Mehlsen J, et al. A 9-
cancer program. BMC Cancer. (2019) 19:1–12. doi: 10.1186/s12885-019-6388-4 valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J
8. Campos-Romero A, Anderson KS, Longatto-Filho A, Luna-Ruiz Esparza MA, Med. (2015) 372:711–23. doi: 10.1056/nejmoa1405044
Morá n-Portela DJ, Castro-Mené ndez JA, et al. The burden of 14 hr-HPV genotypes in 26. Palmer T, Wallace L, Pollock KG, Cuschieri K, Robertson C, Kavanagh K, et al.
women attending routine cervical cancer screening in 20 states of Mexico: a cross- Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine
sectional study. Sci Rep. (2019) 9:1–10. doi: 10.1038/s41598-019-46543-8 at age 12-13 in Scotland: Retrospective population study. BMJ. (2019) 365:1–10.
9. Secretarı́a de Salud. Norma Oficial Mexicana NOM-014-SSA2-1994,Para la doi: 10.1136/bmj.l1161
prevenció n, detecció n, diagnó stico, tratamiento, control y vigilancia espidemioló gica 27. Lei J, Ploner A, Elfström KM, Wang J, Roth A, Fang F, et al. HPV vaccination
del cá ncer cervico uterino. D Of La Fed. (2006) 52:52–70. and the risk of invasive cervical cancer. N Engl J Med. (2020) 383:1340–8. doi: 10.1056/
10. Secretarı́a de Salud. Prevenció n y Control del Cá ncer de la Mujer 2013 - 2018. D nejmoa1917338
Of La Fed. (2018) 98:1–98. Available at: http://cnegsr.salud.gob.mx/contenidos/ 28. Patel C, Brotherton JML, Pillsbury A, Jayasinghe S, Donovan B, Macartney K,
descargas/cama/PrevencionyControldelCancerdelaMujer_2013_2018.pdf. et al. The impact of 10 years of human papillomavirus (HPV) vaccination in Australia:
11. Bedell SL, Goldstein LS, Goldstein AR, Goldstein AT. Cervical cancer screening: what additional disease burden will a nonavalent vaccine prevent? Euro Surveill. (2018)
past, present, and future. Sex Med Rev. (2020) 8:28–37. doi: 10.1016/j.sxmr.2019.09.005 23(41):pii=1700737. doi: 10.2807/1560-7917.ES.2018.23.41.1700737
12. Garland SM, Kjaer SK, Muñoz N, Block SL, Brown DR, DiNubile MJ, et al. Impact 29. Markowitz LE, Drolet M, Lewis RM, Lemieux-Mellouki P, Pé rez N, Jit M, et al.
and effectiveness of the quadrivalent human papillomavirus vaccine: A systematic review of Human papillomavirus vaccine effectiveness by number of doses: Updated systematic
10 years of real-world experience. Clin Infect Dis. (2016) 63:519–27. doi: 10.1093/cid/ciw354 review of data from national immunization programs. Vaccine. (2022) 40:5413–32.
13. Ferrer HB, Trotter C, Hickman M, Audrey S. Barriers and facilitators to HPV doi: 10.1016/j.vaccine.2022.06.065
vaccination of young women in high-income countries: A qualitative systematic review and 30. Schwarz TF, Huang L-M, Valencia A, Panzer F, Chiu C-H, Decreux A, et al. A
evidence synthesis. BMC Public Health. (2014) 14:1–22. doi: 10.1186/1471-2458-14-700 ten-year study of immunogenicity and safety of the AS04-HPV-16/18 vaccine in
14. Prudden HJ, Achilles SL, Schocken C, Broutet N, Canfell K, Akaba H, et al. adolescent girls aged 10-14 years. Hum Vaccines Immunother. (2019) 15:1970–9.
Understanding the public health value and defining preferred product characteristics doi: 10.1080/21645515.2019.1625644
for therapeutic human papillomavirus (HPV) vaccines: World Health Organization 31. Shi L-W, Li J, Yu B-W, Huang L-R, Li K, Ji M, et al. Safety and immunogenicity
consultations, October 2021—March 2022. Vaccine. (2022) 40:5843–55. doi: 10.1016/ of a bivalent HPV16/18 vaccine in Chinese females. Hum Vaccines Immunother. (2023)
j.vaccine.2022.08.020 19:1–10. doi: 10.1080/21645515.2023.2209001
15. Bruni L, Saura-Lá zaro A, Montoliu A, Brotons M, Alemany L, Diallo MS, et al. 32. Bissett SL, Godi A, Jit M, Beddows S. Seropositivity to non-vaccine incorporated
HPV vaccination introduction worldwide and WHO and UNICEF estimates of genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review
national HPV immunization coverage 2010–2019. Prev Med (Baltim). (2021) and meta-analysis. Vaccine. (2017) 35:3922–9. doi: 10.1016/j.vaccine.2017.06.028
144:106399. doi: 10.1016/j.ypmed.2020.106399 33. Stanley M, Joura E, Yen GP, Kothari S, Luxembourg A, Saah A, et al. Systematic
16. Ç uburu N, Kim R, Guittard GC, Thompson CD, Day PM, Hamm DE, et al. A literature review of neutralizing antibody immune responses to non-vaccine targeted
prime-pull-amplify vaccination strategy to maximize induction of circulating and high-risk HPV types induced by the bivalent and the quadrivalent vaccines. Vaccine.
genital-resident intraepithelial CD8+ Memory T cells. J Immunol. (2019) 202:1250– (2021) 39:2214–23. doi: 10.1016/j.vaccine.2021.01.060
64. doi: 10.4049/jimmunol.1800219 34. De Vincenzo R, Conte C, Ricci C, Scambia G, Capelli G. Long-term efficacy and
17. Allanson ER, Schmeler KM. Cervical cancer prevention in low- and middle- safety of human papillomavirus vaccination. Int J Womens Health. (2014) 6:999–1010.
income countries. Clin Obstet Gynecol. (2021) 64(3):501–18. doi: 10.1097/ doi: 10.2147/IJWH.S50365
GRF.0000000000000629 35. Brown DR, Joura EA, Yen GP, Kothari S, Luxembourg A, Saah A, et al.
18. Dorji T, Nopsopon T, Tamang ST, Pongpirul K. Human papillomavirus Systematic literature review of cross-protective effect of HPV vaccines based on data
vaccination uptake in low-and middle-income countries: a meta-analysis. from randomized clinical trials and real-world evidence. Vaccine. (2021) 39:2224–36.
EClinicalMedicine. (2021) 34:100836. doi: 10.1016/j.eclinm.2021.100836 doi: 10.1016/j.vaccine.2020.11.076
19. Prabhu PR, Carter JJ, Galloway DA. B cell responses upon human 36. Bergman H, Buckley BS, Villanueva G, Petkovic J, Garritty C, Lutje V, et al.
papillomavirus (HPV) infection and vaccination. Vaccines. (2022) 10:837. Comparison of different human papillomavirus (HPV) vaccine types and dose
doi: 10.3390/vaccines10060837 schedules for prevention of HPV-related disease in females and males. Cochrane
20. Barbara M, Bharat M, Nam PT, Jayne K, Chen A, Alvarez RD. Emerging human Database Syst Rev. (2019) 2019. doi: 10.1002/14651858.CD013479
papillomavirus vaccines. Expert Opin Emerg Drugs. (2012) 10:469–92. doi: 10.1517/ 37. Sabeena S, Bhat PV, Kamath V, Arunkumar G. Global human papilloma virus
14728214.2012.744393 vaccine implementation: An update. J Obstet Gynaecol. (2018) 44:989–97. doi: 10.1111/
21. World Health Organization. Human papillomavirus vaccines: WHO position jog.13634
paper (2022 update) –Vaccins contre les papillomavirus humains: note de synthèse de 38. Sutcuoglu B. Efficacy of the HPV vaccine in the secondary prevention of cervical
l’OMS (mise à jour de 2022). Wkly Epidemiol Rec. (2022) 97:645–72. dysplasia in patients undergoing surgery. EJMI. (2023) 7:181–7. doi: 10.14744/ejmi.2023.69727
22. Herrero R, Gonzá lez P, Markowitz LE. Present status of human papillomavirus 39. Eriksen DO, Jensen PT, Schroll JB, Hammer A. Human papillomavirus
vaccine development and implementation. Lancet Oncol. (2015) 16:e206–16. vaccination in women undergoing excisional treatment for cervical intraepithelial
doi: 10.1016/S1470-2045(14)70481-4 neoplasia and subsequent risk of recurrence: A systematic review and meta-analysis.
23. Brotherton JM, Budd A, Rompotis C, Bartlett N, Malloy MJ, Andersen RL, et al. Acta Obstet Gynecol Scand. (2022) 101:597–607. doi: 10.1111/aogs.14359
Is one dose of human papillomavirus vaccine as effective as three?: A national cohort 40. Di Donato V, Caruso G, Bogani G, Cavallari EN, Palaia G, Perniola G, et al. HPV
analysis. Papillomavirus Res. (2019) 8:100177. doi: 10.1016/j.pvr.2019.100177 Vaccination after Primary Treatment of HPV-Related Disease across Different Organ
24. Drolet M, Bé nard E, Pé rez N, Brisson M, Ali H, Boily M-C, et al. Population- Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis. Vaccines. (2022)
level impact and herd effects following the introduction of human papillomavirus 10:1–16. doi: 10.3390/vaccines10020239

Frontiers in Oncology 06 frontiersin.org