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Management of CIN and HPV Eradication Strategies for the Prevention...
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Management of CIN and HPV Eradication Strategies for the Prevention of Uterine Cervical Cancer

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

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 18069

Special Issue Editor

Dr. Masaru Sakamoto

E-Mail Website
Guest Editor
1. Department of Gynecology, Sasaki Foundation Kyoundo Hospital, Tokyo, Japan
2. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
Interests: HPV pathogenesis; HPV preventive vaccine; L1-VLP vaccine; HPV therapeutic vaccine; PDT effect against HPV infection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Around the world, the number of cervical cancer cases per year is estimated as 570,000 women, with 310,000 women dying of cervical cancer as in 2018. In Japan, the number of cervical cancer cases in young women aged 20–39 is increasing, as is the mortality rate, with a tendency which is totally different from that in the rest of world.

In 2017, about 2800 women across Japan died of cervical cancer, among whom more than 1200 were under the age of 65, the so-called active generation. This is an extremely alarming trend. In addition, the active recommendation of an HPV vaccine that can effectively prevent cervical cancer has been withheld for a while, and in fact, HPV vaccination has been suspended for the public in Japan.

Meanwhile, data on the safety and efficacy of HPV vaccines have been collected from Japan and overseas. Therefore, the Japan Society of Obstetrics and Gynecology requested prompt resumption of active recommendation of the HPV vaccine.

In this Special Issue, the main aim is to help to prevent uterine cervical cancer. For the prevention of uterine cervical cancer, there are two categories, i.e., primary and secondary prevention. As primary prevention of uterine cervical cancer, HPV vaccines are used for the prevention of HPV infection worldwide. This category includes efficacy and safety of the 9-valent vaccine against cervical cancer, the current startus of 4-valent vaccines in Japan and issues with their spread, and development and clinical application of a broad-spectrum L2VLP HPV vaccine.

As secondary prevention of uterine cervical cancer, diagnosis and management of CIN is performed. This category includes diagnosis of CIN using conventional methods, i.e., cytology, HPV test, and histology, diagnosis of CIN using new methods, i.e., immune-cytochemistry and miRNA., and obstetric issues of cervical conization used for the diagnosis and treatment of CIN, treatment of CIN using PDT with photofrin and laserphyrin, treatment of CIN using 5ALA-PDT, the therapeutic effect of PDT on HPV infection, and treatment of CIN with a new method, HPV therapeutic vaccines.

We are interested in a broad area of research, focusing primarily on the management of CIN and HPV eradication strategies for the prevention of uterine cervical cancer. In addition, we are calling for manuscripts dealing with vaccine trials (preclinical and clinical) and strategies to develop a more effective HPV vaccine. We aim to present a combination of manuscripts dealing with different vital aspects of HPV, which can be exploited to develop more effective eradication strategies for HPV infection.

Dr. Masaru Sakamoto
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • 4-valent HPV vaccine
  • 9-valent HPV vaccine
  • HPV L1-VLP vaccine
  • HPV L2-VLP vaccine
  • HPV therapeutic vaccine
  • CIN
  • PDT

Published Papers (5 papers)

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Research

11 pages, 628 KiB  
Article
Changes in HPV16/18 Prevalence among Unvaccinated Women with Cervical Intraepithelial Neoplasia in Japan: Assessment of Herd Effects following the HPV Vaccination Program
by Mamiko Onuki, Kasumi Yamamoto, Hideaki Yahata, Hiroyuki Kanao, Koji Horie, Katsuyuki Konnai, Ai Nio, Kazuhiro Takehara, Shoji Kamiura, Naotake Tsuda, Yuji Takei, Shogo Shigeta, Hidekatsu Nakai, Hiroyuki Yoshida, Takeshi Motohara, Tatsuya Kato, Keiichiro Nakamura, Junzo Hamanishi, Nobutaka Tasaka, Mitsuya Ishikawa, Nobuhiro Kado, Yusuke Taira, Mayuyo Mori, Takashi Iwata, Fumiaki Takahashi, Iwao Kukimoto, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto and for the MINT Study Groupadd Show full author list remove Hide full author list
Vaccines 2022, 10(2), 188; https://doi.org/10.3390/vaccines10020188 - 25 Jan 2022
Cited by 2 | Viewed by 3091
Abstract
Since the human papillomavirus (HPV) vaccination program for Japanese girls aged 12–16 years began in 2010, vaccination uptake has been low in women born before 1993 but high (approximately 70%) in those born during 1994–1999. We previously compared the prevalence of vaccine types [...] Read more.
Since the human papillomavirus (HPV) vaccination program for Japanese girls aged 12–16 years began in 2010, vaccination uptake has been low in women born before 1993 but high (approximately 70%) in those born during 1994–1999. We previously compared the prevalence of vaccine types HPV16 and HPV18 in cervical intraepithelial neoplasia grade 1–3 (CIN1–3) or adenocarcinoma in situ (AIS) between vaccinated and unvaccinated cohorts and found direct protection effects among vaccinated women in Japan. In this study, we focused on changes in HPV16/18 prevalence among “unvaccinated” cohorts with CIN/AIS. We analyzed HPV16/18 prevalence among 5051 unvaccinated women aged <40 years, newly diagnosed with CIN/AIS during 2012–2021 for time trends. Declining trends in HPV16/18 prevalence over 9 years were observed in CIN1 (36.0–10.0%, Ptrend = 0.03) and CIN2–3/AIS (62.5–36.4%, Ptrend = 0.07) among women aged <25 years. HPV16/18 prevalence in CIN1 and CIN2–3/AIS diagnosed at age 20–24 years was lower in 1994–1999 birth cohorts compared with 1988–1993 birth cohorts (4.5% vs. 25.7% for CIN1 and 40.0% vs. 58.1% for CIN2–3/AIS, both p = 0.04). Significant reduction in HPV16/18 prevalence among young unvaccinated women with CIN1 and CIN2–3/AIS suggests herd effects of HPV vaccination in Japan. Full article
(This article belongs to the Special Issue Management of CIN and HPV Eradication Strategies for the Prevention of Uterine Cervical Cancer)
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13 pages, 1151 KiB  
Article
A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)
by Yuji Ikeda, Katsuyuki Adachi, Kensuke Tomio, Satoko Eguchi-Kojima, Tetsushi Tsuruga, Mayuyo Uchino-Mori, Ayumi Taguchi, Atsushi Komatsu, Takeshi Nagamatsu, Katsutoshi Oda, Ai Kawana-Tachikawa, Yukari Uemura, Shizunobu Igimi, Yutaka Osuga, Tomoyuki Fujii and Kei Kawana
Vaccines 2021, 9(4), 329; https://doi.org/10.3390/vaccines9040329 - 01 Apr 2021
Cited by 13 | Viewed by 2703
Abstract
Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV); high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial [...] Read more.
Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV); high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial of GLBL101c treatment for CIN2 in 40 patients with HPV16-positive CIN2 who were 1:1 randomized to receive GLBL101c (1 g/daily) or placebo for 5 days at 1, 2, 4, and 8 weeks. No differences were noted between the GLBL101c and placebo groups for patient background and adverse events. Moreover, no statistically significant difference was noted between the two groups at the primary endpoint, pathological regression after 16 weeks of the first oral dose; however, only in the GLBL101c group, two patients had complete regression (CR; regression to normal within 16 weeks). IFNγ production was significantly correlated with the number of spots identified by the interferon gamma enzyme-linked immunospot (IFNγ-ELISPOT) assay using cervical lymphocytes (CxLs) or peripheral blood mononuclear cells. In the two cases of CR, E7-specific Th1 immune responses were observed at week 16. Therefore, we concluded as a novel Lactobacillus-based vaccine with stronger immunogenicity than GLBL101c should be developed. Full article
(This article belongs to the Special Issue Management of CIN and HPV Eradication Strategies for the Prevention of Uterine Cervical Cancer)
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11 pages, 1448 KiB  
Article
Assessing the Long-Term Role of Vaccination against HPV after Loop Electrosurgical Excision Procedure (LEEP): A Propensity-Score Matched Comparison
by Giorgio Bogani, Francesco Raspagliesi, Francesco Sopracordevole, Andrea Ciavattini, Alessandro Ghelardi, Tommaso Simoncini, Marco Petrillo, Francesco Plotti, Salvatore Lopez, Jvan Casarin, Maurizio Serati, Ciro Pinelli, Gaetano Valenti, Alice Bergamini, Barbara Giannella, Andrea Dell’Acqua, Ermelinda Monti, Paolo Vercellini, Giovanni D’ippolito, Lorenzo Aguzzoli, Vincenzo D Mandato, Paola Carunchio, Gabriele Carlifante, Luca Giannella, Cono Scaffa, Francesca Falcone, Stefano Ferla, Chiara Borghi, Antonino Ditto, Mario Malzoni, Andrea Giannini, Maria Giovanna Salerno, Viola Liberale, Biagio Contino, Cristina Donfrancesco, Michele Desiato, Anna Myriam Perrone, Giulia Dondi, Pierandrea De Iaco, Umberto Leone Roberti Maggiore, Mauro Signorelli, Valentina Chiappa, Simone Ferrero, Giuseppe Sarpietro, Maria G Matarazzo, Antonio Cianci, Sara Bocio, Simona Ruisi, Rocco Guerrisi, Claudia Brusadelli, Lavinia Mosca, Raffaele Tinelli, Rosa De Vincenzo, Gian Franco Zannoni, Gabriella Ferrandina, Salvatore Dessole, Roberto Angioli, Stefano Greggi, Arsenio Spinillo, Fabio Ghezzi, Nicola Colacurci, Margherita Fischetti, Annunziata Carlea, Fulvio Zullo, Ludovico Muzii, Giovanni Scambia, Pierluigi Benedetti Panici and Violante Di Donatoadd Show full author list remove Hide full author list
Vaccines 2020, 8(4), 717; https://doi.org/10.3390/vaccines8040717 - 01 Dec 2020
Cited by 31 | Viewed by 3874
Abstract
Background: Primary prevention through vaccination is a prophylactic approach aiming to reduce the risk of developing human papillomavirus (HPV)-related lesions. No mature and long-term data supported the adoption of vaccination in women undergoing conization. Methods: This is a retrospective multi-institutional study. Charts [...] Read more.
Background: Primary prevention through vaccination is a prophylactic approach aiming to reduce the risk of developing human papillomavirus (HPV)-related lesions. No mature and long-term data supported the adoption of vaccination in women undergoing conization. Methods: This is a retrospective multi-institutional study. Charts of consecutive patients undergoing conization between 2010 and 2014 were collected. All patients included had at least 5 years of follow-up. We compared outcomes of patients undergoing conization plus vaccination and conization alone. A propensity-score matching algorithm was applied in order to reduce allocation biases. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, charts of 1914 women were analyzed. The study group included 116 (6.1%) and 1798 (93.9%) women undergoing conization plus vaccination and conization alone, respectively. Five-year recurrence rate was 1.7% (n = 2) and 5.7% (n = 102) after conization plus vaccination and conization alone, respectively (p = 0.068). After the application of a propensity-score matching, we selected 100 patients undergoing conization plus vaccination and 200 patients undergoing conization alone. The crude number of recurrences was 2 (2%) and 11 (5.5%) for patients undergoing conization plus vaccination and conization alone, respectively (p = 0.231). Vaccination had no impact on persistent lesions (no negative examination between conization and new cervical dysplasia; p = 0.603), but reduced the risk of recurrent disease (patients who had at least one negative examination between conization and the diagnosis of recurrent cervical dysplasia; p = 0.031). Conclusions: Patients having vaccination experience a slightly lower risk of recurrence than women who had not, although not statistically significantly different. Further evidence is needed to assess the cost effectiveness of adopting vaccination in this setting. Full article
(This article belongs to the Special Issue Management of CIN and HPV Eradication Strategies for the Prevention of Uterine Cervical Cancer)
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13 pages, 593 KiB  
Article
HPV Vaccination as Adjuvant to Conization in Women with Cervical Intraepithelial Neoplasia: A Study under Real-Life Conditions
by Marta del Pino, Cristina Martí, Ines Torras, Carla Henere, Meritxell Munmany, Lorena Marimon, Adela Saco, Aureli Torné and Jaume Ordi
Vaccines 2020, 8(2), 245; https://doi.org/10.3390/vaccines8020245 - 23 May 2020
Cited by 31 | Viewed by 5121
Abstract
Background: Recent studies have shown preliminary evidence that vaccination against human papillomavirus (HPV) could decrease the risk of persistent/recurrent HSIL in women treated for high-grade cervical intraepithelial lesion (HSIL). We aimed to determine the benefits of HPV vaccination in patients undergoing conization for [...] Read more.
Background: Recent studies have shown preliminary evidence that vaccination against human papillomavirus (HPV) could decrease the risk of persistent/recurrent HSIL in women treated for high-grade cervical intraepithelial lesion (HSIL). We aimed to determine the benefits of HPV vaccination in patients undergoing conization for HSIL in real-life conditions and evaluate vaccination compliance associated with different funding policies. Methods: From January 2013 to July 2018, 265 women underwent conization in our center. From January 2013 to July 2017, treated patients (n = 131) had to pay for the vaccine, whereas after July 2017 the vaccine was publicly funded and free for treated women (n = 134). Post-conization follow-up controls were scheduled every six months with a Pap smear, HPV testing, and a colposcopy. Results: 153 (57.7%) women accepted vaccination (vaccinated group), and 112 (42.3%) refused the vaccine (non-vaccinated group). Persistent/recurrent HSIL was less frequent in vaccinated than in non-vaccinated women (3.3% vs. 10.7%, p = 0.015). HPV vaccination was associated with a reduced risk of persistent/recurrent HSIL (OR 0.2, 95%CI: 0.1–0.7, p = 0.010). Vaccination compliance increased when the vaccine was publicly funded (from 35.9% [47/131] to 79.1% [106/134], p < 0.001). Conclusions: HPV vaccination in women undergoing conization is associated with a 4.5-fold reduction in the risk of persistent/recurrent HSIL. Vaccination policies have an important impact on vaccination compliance. Full article
(This article belongs to the Special Issue Management of CIN and HPV Eradication Strategies for the Prevention of Uterine Cervical Cancer)
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11 pages, 885 KiB  
Article
Prevalence, Genotype Distribution, and Predictors against HPV Infections Targeted by 2-, 4-, 9-Valent HPV Vaccines among Japanese Males
by Yukimasa Matsuzawa, Tadaichi Kitamura, Motofumi Suzuki, Yasuhiro Koyama and Kazuyoshi Shigehara
Vaccines 2020, 8(2), 221; https://doi.org/10.3390/vaccines8020221 - 14 May 2020
Cited by 6 | Viewed by 2445
Abstract
Objectives: Epidemiological reports of sexual life and human papilloma virus (HPV) infection among Japanese men are scarce, and the necessity of HPV vaccines for males is regarded as a controversial topic in Japan. The objective of this study is to determine the prevalence, [...] Read more.
Objectives: Epidemiological reports of sexual life and human papilloma virus (HPV) infection among Japanese men are scarce, and the necessity of HPV vaccines for males is regarded as a controversial topic in Japan. The objective of this study is to determine the prevalence, genotype distribution, and risk factors against HPV infections targeted by bivalent (2v), quadrivalent (4v), and 9-valent (9v) HPV vaccines among Japanese male patients who visited our urological clinics. Material and Methods: The study population consisted of 798 males aged 20 to 95 years (mean ± standard deviation, 55.4 ± 19.5 years). We collected scraping samples from the glans penis using cotton swabs from all patients for genotyping of HPVs. We compared patients’ characteristics and detected HPV genotypes in order to determine the risk factors against HPV infections. Results: Of 798 participants, 198 participants (198/798; 24.8%) had at least one genotype of any HPV infection. The total number of detected HPV genotypes was 328. Of 328 genotypes, 30% (n = 99; 99/328) were 9v HPV genotypes. Most frequently detected types of high-risk HPV infection were type 52 (n = 40; 40/328; 12.2%). Number of lifetime sex partners (≥21) and present or history of sexually transmitted infections were found to be predictors of any HPV infection with adjusted odds ratios of 3.106 (95% confidence interval (CI), 1.593–6.509) and 1.894 (95% CI, 1.185–3.026), respectively. Age of sex initiation was a predictor of 2v and 4v HPV infections with adjusted odds ratios of 100 (95% CI, 1.013–25.673) and 2.676 (95% CI, 1.037–6.905), respectively. Number of lifetime sex partners (≥21) was a predictor of 9v HPVs with adjusted odds ratios of 2.397 (95% CI, 1.060–5.424). Conclusions: Approximately, a quarter of Japanese male patients who visited urological clinics were exposed to HPV. Moreover, from the perspective of our multivariate logistic regression analysis, some kinds of sexual behavior aggravate the risk of typical HPV genotypes infections. Full article
(This article belongs to the Special Issue Management of CIN and HPV Eradication Strategies for the Prevention of Uterine Cervical Cancer)
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