Submit to Vaccines Review for Vaccines Propose a Special Issue

Journal Menu

Journal Browser

Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Human Papillomavirus Vaccines".

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 21866

Share This Special Issue

Special Issue Editor

Dr. Ignacio Zapardiel

E-Mail Website1 Website2
Guest Editor

Gynecologic Oncology Unit, La Paz University Hospital, 28046 Madrid, Spain
Interests: Surgical oncology; fertility preservation treatments; rare cancers; uterine sarcoma; vulvar cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The HPV vaccine has been established as the best option among prevention strategies to avoid the development of cervical cancer and other vulvar and vaginal diseases in women worldwide. During the last decade, we have observed a great evolution in HPV vaccines, such as the increase in HPV serotype coverage, a strategic implementation expanding to more age ranges, the inclusion of more targeted proteins, and other advances. Investigating the role of HPV vaccines may open a new horizon in the fight against cervical cancer, vulvar and vaginal cancer, and against preinvasive lesions. In addition, the current status of HPV vaccines, and the real coverage rates among different European countries, may give us an idea of the problem and a starting point from which we may get ahead.

All these topics make this Special Issue an opportunity to communicate promising research lines, new concepts, and results of immunization on different populations. We hope all authors and researchers consider this opportunity to publish their work in this Vaccines Special Issue.

Dr. Ignacio Zapardiel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

human papillomavirus
preinvasive lesions
vulvar disease
cervical intraepithelial neoplasia
vaginal neoplasia

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (8 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review, Other

13 pages, 1752 KB

Open AccessArticle

Prophylactic HPV Vaccination in Gynaecological Practice: Recommendations, Practices, and Challenges Reported in the ESGO-PERCH HPV Survey

by Joanna Kacperczyk-Bartnik, Marc Arbyn, Sophie Denoël, Esra Bilir, Nina Dhollander, Zoia Razumova, Khayal Gasimli, Andrej Cokan, Houssein El Hajj, Tibor Andrea Zwimpfer, Maria Kyrgiou, Murat Gultekin and Nicolò Bizzarri

Vaccines 2026, 14(3), 269; https://doi.org/10.3390/vaccines14030269 - 16 Mar 2026

Viewed by 1084

Abstract

Background/Objectives: HPV vaccination is highly effective in preventing HPV-related cancers when administered before viral exposure. However, vaccination practices for patients already diagnosed with gynaecological cancers remain poorly characterized. Understanding clinicians’ perspectives and barriers is essential for optimizing preventive strategies in oncologic care. Methods: We conducted an international, web-based survey among members of the European Society of Gynaecological Oncology (ESGO) and the European Network of Young Gynaecological Oncologists (ENYGO). The questionnaire explored clinicians’ attitudes, practices, and perceived obstacles regarding HPV vaccination in patients with gynaecological cancer or pre-invasive disease across multiple clinical scenarios and age groups. Results: A total of 149 respondents from 33 countries completed the survey. Most clinicians supported HPV vaccination for patients treated for cervical precancer (78–82% for patients under 45 years), and even for invasive cervical cancer (57–62%). Recommendations varied by patients’ age, cancer type, and treatment status. For endometrial and ovarian cancer, endorsement ranged from 16% to 53%, depending on patient age. Timing of vaccination was a point of divergence: some clinicians favoured vaccination immediately after treatment for CIN2+, while others recommended delaying vaccination depending on HPV test results. Reported barriers discouraging HPV vaccination recommendations included misinformation (69.8%), lack of patient education materials (52.3%), and time constraints (48.3%), alongside economic factors and uncertainty about efficacy in oncologic settings. Conclusions: The survey shows that HPV vaccination is often recommended beyond evidence-supported indications. Randomized trials have not demonstrated a reduction in CIN2+ recurrence with adjuvant vaccination, and no evidence supports vaccination in women with invasive gynaecological cancers. These findings reveal a gap between clinical practice and available evidence, highlighting the need for clearer, evidence-based guidance. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

► Show Figures

Figure 1

11 pages, 688 KB

Open AccessArticle

Effect of HPV Adult Vaccination on Serum Anti-Müllerian Hormone Levels: Paired Measurements in a Retrospective Cohort

by Ali Can Gunes, Muhammed Onur Atakul, Utku Akgor, Gonca Ozten Dere, Murat Cengiz, Haticegul Tuncer, Betul Gungor Serin, Mehmet Kabacam, Hakan Aydinli and Murat Gultekin

Vaccines 2026, 14(3), 233; https://doi.org/10.3390/vaccines14030233 - 3 Mar 2026

Viewed by 870

Abstract

Background: Concerns that human papillomavirus (HPV) vaccination may adversely affect ovarian reserve contribute to vaccine hesitancy, yet longitudinal data with paired anti-Müllerian hormone (AMH) measurements are limited. We evaluated whether HPV vaccination was associated with short-term changes in AMH compared with an unvaccinated control group. Methods: In this retrospective cohort, women aged 18–45 years who completed a three-dose 9-valent HPV vaccination (Gardasil 9®, Merck Sharp & Dohme LLC, West Point/Pennsylvania/USA) schedule and had AMH measured before dose 1 and after dose 3 were compared with unvaccinated controls who had two AMH measurements during routine gynecologic evaluation. AMH change was summarized as absolute change (ΔAMH), percent change, and log change. To compare rates of AMH change while accounting for heterogeneous follow-up and confounding, AMH was analyzed on the natural log scale using a linear mixed-effects model with a random intercept for participant and fixed effects for time (years), group, and a time × group interaction, adjusted for age, current smoking, gravidity, and parity. Annual percent change was derived from model coefficients. Prespecified sensitivity analyses repeated the primary model under follow-up restrictions and after restricting baseline AMH to 1.0–5.0 ng/mL. Results: The cohort included 158 vaccinated and 106 control women. Baseline AMH was similar between groups (median 1.88 vs. 1.94 ng/mL), while the follow-up interval was shorter in vaccinated women (6.7 vs. 8.9 months). Unadjusted AMH decline was smaller in vaccinated women (median ΔAMH −0.13 vs. −0.27 ng/mL; p = 0.015; median percent change −10.9% vs. −20.6%; p = 0.006). In the adjusted mixed-effects model, controls showed an estimated AMH decline of −27.6% per year (95% CI −35.5% to −18.7%; p < 0.001). The time × group interaction was positive (β = 0.170, 95% CI 0.027 to 0.312; p = 0.020), corresponding to a slope ratio of 1.185 (95% CI 1.02–1.366) and an implied annual change of −14.2% per year (95% CI −21.0% to −6.7%) in vaccinated women. Results were broadly consistent in follow-up-restricted sensitivity analyses; however, in the baseline AMH 1.0–5.0 ng/mL restricted cohort (vaccinated n = 82, control n = 67), the interaction was attenuated and not statistically significant (β = 0.082, p = 0.237). Conclusions: In this retrospective cohort with paired AMH measurements, HPV vaccination was not associated with evidence of clinically meaningful short-term impairment in ovarian reserve as assessed by AMH. Observed differences in AMH alterations were modest and should be interpreted cautiously, given residual confounding, measurement variability, and reduced precision in restricted-cohort analyses. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

► Show Figures

Figure 1

14 pages, 270 KB

Open AccessArticle

HPV Vaccination and HPV Outcomes After LEEP: A Retrospective Population-Based Cohort Study from Northern Norway, 2022–2024

by Sveinung Wergeland Sørbye, Mona Antonsen and Elin Richardsen

Vaccines 2026, 14(1), 44; https://doi.org/10.3390/vaccines14010044 - 30 Dec 2025

Cited by 1 | Viewed by 1270

Abstract

Background/Objectives: Women treated with loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk of HPV detection during follow-up. We assessed whether HPV vaccination was associated with HPV positivity at the first post-treatment follow-up after LEEP. Methods: This retrospective population-based cohort included women aged 20–79 years treated by LEEP in Troms and Finnmark, Norway, during 2022–2024 (n = 1052). Vaccination status, timing, and vaccine product were obtained from the national immunization register (SYSVAK). Follow-up HPV results (overall HPV, HPV16, HPV18, and pooled other HPV types; Roche cobas 4800 channels) were retrieved from SymPathy. Results: Overall, 329/1052 women (31.3%) were HPV-positive at first follow-up. HPV positivity was 37.7% (200/530) among unvaccinated women and 24.7% (129/522) among vaccinated women (ARR 13.0 percentage points; 95% CI 7.5–18.6; RR 0.655; 95% CI 0.544–0.788; p = 5.2 × 10⁻⁶). HPV16 was detected in 5.9% vs. 9.4% (p = 0.0335), and pooled other HPV types in 18.0% vs. 28.7% (p = 4.3 × 10⁻⁵); HPV18 did not differ (2.9% vs. 2.5%; p = 0.671). In adjusted analyses, vaccination in the year of LEEP was associated with lower risk of follow-up HPV positivity (aRR 0.592; 95% CI 0.444–0.789; p = 0.000348). Conclusions: HPV vaccination before the first post-treatment follow-up was associated with lower HPV positivity after LEEP. As this outcome is a surrogate endpoint and residual confounding is possible, studies with standardized follow-up and long-term clinical endpoints are needed. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

► Show Figures

Figure 1

10 pages, 524 KB

Open AccessArticle

High-Grade Vaginal Intraepithelial Neoplasia: Clinical Profile, HPV Vaccination Status, and Treatment Outcomes at Two Italian Referral Centers

by Niccolò Gallio, Mario Preti, Renzo Boldorini, Cristina Cavagnetto, Fulvio Borella, Federica Bevilacqua, Ilaria Barbierato, Raffaella Ribaldone, Enrica Bovio, Chiara Airoldi, Valentino Remorgida, Luca Marozio and Alberto Revelli

Vaccines 2025, 13(11), 1089; https://doi.org/10.3390/vaccines13111089 - 24 Oct 2025

Cited by 3 | Viewed by 1726

Abstract

Background: There is limited available data about the natural history and clinical characteristics of patients affected by high-grade vaginal intraepithelial neoplasia (or vaginal intraepithelial neoplasia 2/3 or vaginal high-grade squamous intraepithelial lesion, HSIL). The aim of the study was to review clinical characteristics and treatment outcomes of a large cohort of patients with vaginal HSIL. Methods: A retrospective analysis was performed for patients with histologically confirmed VaIN 2/3 treated at two Italian referral centers from 2003 to 2022. Demographics, referring cytology, associated cervical and vulvar HSIL treatment modalities, follow-up visits, and vaccination status were recorded. The primary outcome was risk of recurrence; the secondary outcome was risk of progression to invasive carcinoma after treatment. Results: 323 women were included in the analysis: 69.7% (225) had VaIN2, and 30.3% (98) had VaIN3. Mean age at diagnosis was 55.43 years (range 24–93 years). 20.4% had a previous hysterectomy, mainly for cervical intraepithelial neoplasia (CIN)/invasive squamous carcinoma (64.6%). In total, 55.2% underwent ablative therapy, and 44.8% underwent excisional treatment. Over a mean follow-up of 62.43 months, 22.0% of patients recurred as vaginal HSIL. At univariate analysis older age, VaIN grade 3, previous hysterectomy, associated cervical lesions, associated vulvar HSIL, and excisional treatment were significantly associated with increased risk of recurrence. At multivariate analysis, only hysterectomy and excisional treatment maintained significance. Five patients progressed to invasive vaginal carcinoma, with a median time to invasion of 87.1 months. Conclusions: The risk of recurrence of vaginal HSIL is higher in patients treated with excisional methods and/or those who have undergone hysterectomy for both benign and preinvasive lesions. Long-term follow-up is essential to monitor clinical outcomes and prevent disease progression. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

► Show Figures

Figure 1

9 pages, 184 KB

Open AccessArticle

HPV E6/E7 mRNA Testing in the Follow-Up of HPV-Vaccinated Patients After Treatment for High-Grade Cervical Intraepithelial Neoplasia

by Adolfo Loayza, Alicia Hernandez, Ana M. Rodriguez, Belen Lopez, Cristina Gonzalez, David Hardisson, Itziar de la Pena, Maria Serrano, Rocio Arnedo and Ignacio Zapardiel

Vaccines 2025, 13(8), 823; https://doi.org/10.3390/vaccines13080823 - 31 Jul 2025

Viewed by 3334

Abstract

Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

Review

Jump to: Research, Other

27 pages, 498 KB

Open AccessReview

Human Papillomavirus in Reproductive Health and Pregnancy: Clinical Implications, Outcomes, and a Comprehensive Review of Vaccination

by Hasan Volkan Ege, Charlotte Goutallier, Laura Burney Ellis, Houssein El Hajj, Joanna Kacperczyk-Bartnik, Bilal Esat Temiz, Nadja Taumberger, Reda Hemida, Gökçen Ege, Utku Akgör, Zvi Vaknin, Maria Kyrgiou and Murat Gultekin

Vaccines 2026, 14(2), 180; https://doi.org/10.3390/vaccines14020180 - 14 Feb 2026

Viewed by 2152

Abstract

Background/Objectives: Human papillomavirus (HPV) is the most common sexually transmitted virus worldwide and is frequently detected in women of reproductive age. In this population, HPV-related diseases and their management may affect reproductive health and pregnancy outcomes. This narrative review summarizes the current evidence on HPV infection and HPV-related diseases in relation to fertility, pregnancy, and neonatal outcomes, and discusses preventive strategies, with a particular focus on HPV vaccination. Methods: An international, multidisciplinary team of clinicians from the European Society of Gynaecological Oncology (ESGO) Prevention Committee reviewed the literature on HPV, HPV-related diseases, HPV vaccination, and reproductive outcomes, without time restrictions, prioritizing studies judged to meaningfully reflect the available evidence. Results: The most consistent evidence linking HPV-related conditions to adverse pregnancy outcomes relates to the treatment of cervical precancer, particularly excisional procedures, which are associated with an increased risk of preterm birth and mid-trimester pregnancy loss. In contrast, evidence that maternal HPV detection alone causes adverse pregnancy or neonatal outcomes remains limited and inconsistent. Data on HPV infection and subfertility are scarce and heterogeneous. Management of HPV-related lesions during pregnancy remains challenging and requires careful balancing of maternal safety with avoidance of unnecessary interventions. HPV DNA has been detected in neonatal samples, but convincing evidence for clinically relevant vertical transmission is lacking. Available data indicate that inadvertent HPV vaccination shortly before or during pregnancy is not associated with adverse pregnancy outcomes. Conclusions: Current evidence suggests that reproductive risks are more strongly associated with the treatment of HPV-related diseases than with HPV infection itself. Preventive strategies—especially HPV vaccination—remain central to reducing HPV-related disease burden. Although HPV vaccines are not routinely recommended during pregnancy, evidence supports the safety of inadvertent exposure around conception or during gestation, while potential long-term benefits of vaccination regarding reproductive health require further study. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

► Show Figures

Figure 1

16 pages, 256 KB

Open AccessReview

New HPV Vaccines on the Market and Future Trends: A State-of-the-Art Review

by Utku Akgör, Bilal Esat Temiz, Murat Cengiz, Hasan Volkan Ege, Elmar Joura and Murat Gültekin

Vaccines 2026, 14(2), 140; https://doi.org/10.3390/vaccines14020140 - 29 Jan 2026

Cited by 1 | Viewed by 7369

Abstract

Next-generation human papillomavirus (HPV) vaccines encompass newly licensed and emerging formulations that employ alternative production platforms, expanded valency, or novel antigenic targets beyond conventional L1-based vaccines. These vaccines aim to address affordability challenges, supply limitations, and suboptimal vaccination coverage, particularly in low- and middle-income countries. This review aggregates current clinical, immunological, and programme-related evidence on newly licensed vaccines, including the World Health Organization (WHO)-prequalified bivalent formulations (Cecolin^® and Walrinvax^®), the quadrivalent Cervavac^®, and the Escherichia coli-derived nonavalent Cecolin 9^®, which received national licensure in 2025. Additionally, emerging high-valency candidates in Phase I–III trials—9-valent, 11-valent, and 14-valent formulations—are critically assessed. Clinical trials demonstrate that next-generation HPV vaccines provide robust protection; for example, Cecolin^® showed 100% efficacy against HPV-16/18-associated high-grade squamous intraepithelial lesions (HSIL) and up to 97.8% efficacy against persistent HPV infection, while Walrinvax^® demonstrated 78.6% protection against CIN2+ lesions. Cervavac^® showed non-inferior immunogenicity compared with established vaccines. While comparative analyses of efficacy, immunogenicity, and safety indicate that these vaccines are strong alternatives to established products, robust long-term effectiveness and real-world impact data remain essential before full clinical equivalence can be definitively established. Advances in L2-based platforms further aim to broaden cross-type protection, simplify manufacturing, and enable thermostable formulations, thereby enhancing applicability in resource-limited settings. Economic evaluations demonstrating favorable cost-effectiveness emphasize the essential role of next-generation vaccines in improving access and reducing inequity. Overall, innovations in valency, technology, and delivery strategies have the potential to significantly expand global HPV prevention coverage and accelerate progress toward cervical cancer elimination. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

Other

Jump to: Research, Review

17 pages, 473 KB

Open AccessSystematic Review

HPV Exposure in the Gynecological Practice: Time to Call It an Occupational Disease? A Systematic Review of the Literature and ESGO Experts’ Opinion

by Hasan Volkan Ege, Bilal Esat Temiz, Mihaela Grigore, Laura Burney Ellis, Sarah J. Bowden, Belen Lopez-Cavanillas, Mario Preti, Ignacio Zapardiel, Elmar Joura, Murat Gültekin and Maria Kyrgiou

Vaccines 2026, 14(2), 148; https://doi.org/10.3390/vaccines14020148 - 31 Jan 2026

Viewed by 3366

Abstract

Background/Objectives: Persistent human papillomavirus (HPV) infection can lead to malignancies of the cervix, vulva, vagina, penis, anus, and oropharynx. The increasing incidence of HPV-related head and neck cancers has raised concerns regarding potential occupational exposure and transmission risks among healthcare workers. This study aimed to systematically evaluate the evidence on occupational HPV transmission in healthcare settings. Methods: A systematic review of the literature was conducted using three electronic databases (PubMed, Scopus, and Web of Science) from inception to August 2025, following PRISMA 2020 guidelines. A total of 34 studies met the inclusion criteria and were included in the review. Expert opinions and practical recommendations from members of the European Society of Gynaecological Oncology (ESGO) Prevention Committee were included to support interpretation of the results. Results: The available literature on occupational HPV transmission was limited, with a paucity of high-quality studies. Nevertheless, existing data suggest a potential occupational risk, particularly during aerosol or smoke-generating procedures performed for cervical intraepithelial neoplasia or cervical cancer. Several studies reported the detection of HPV DNA in surgical smoke or on instruments used during such procedures, indicating possible exposure among healthcare workers. Conclusions: Although current evidence is insufficient to definitively classify HPV infection as an occupational disease, available data indicate a potential exposure risk for healthcare workers involved in HPV-related procedures. Preventive measures, like personal protective equipment, should be emphasized. HPV vaccination has been recommended by some professional societies for healthcare workers performing gynecological procedures, though further research is needed to evaluate vaccine efficacy beyond the standard age range and its cost-effectiveness in this context. Full article

(This article belongs to the Special Issue Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases)

► Show Figures

Journal Menu

Journal Browser

Role of Human Papillomavirus Vaccines in Cervical and Vulvo-Vaginal Diseases

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI