scholarly journals Human papillomavirus-driven immune deviation: challenge and novel opportunity for immunotherapy

2017 ◽  
Vol 5 (3) ◽  
pp. 69-82 ◽  
Author(s):  
Sigrun Smola ◽  
Connie Trimble ◽  
Peter L. Stern

It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with therapeutic HPV vaccination. Future progress in delivering successful immunotherapy will depend on the configuration of treatment protocols in an insightful and timely combination.

2012 ◽  
Vol 7 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Baudelio Gutierrez ◽  
Anthony Leung ◽  
Kevin Trimell Jones ◽  
Peter Smith ◽  
Randee Silverman ◽  
...  

The human papillomavirus (HPV) vaccine was recently approved for use in males. Certain groups, such as men who have sex with men (MSM), are at increased risk of HPV infection. The purpose of the study was to understand perceptions of HPV and the vaccine among adolescent and young adult males, both heterosexual and MSM. Seventy-six males (45 heterosexual, 31 MSM) completed a questionnaire and participated in a focus group. Overall, 42% had heard of HPV and 39% had heard of the HPV vaccine. Males had moderate to favorable attitudes toward vaccination, although intentions to vaccinate were more neutral. MSM were more knowledgeable, aware, and in control of the decision to vaccinate than heterosexual males. Increasing awareness and knowledge about HPV and the vaccine may be necessary to encourage vaccination; certain subgroups of males may be more receptive to HPV vaccination than others.


Author(s):  
Shang-Ying Hu ◽  
Sabrina H Tsang ◽  
Feng Chen ◽  
Qin-Jing Pan ◽  
Wen-Hua Zhang ◽  
...  

Abstract Background How vaginal infections such as bacterial vaginosis, Candida spp, and Trichomonas vaginalis affect persistence of human papillomavirus (HPV) infection is not well established. Our study aimed to evaluate the association between common vaginal infections and cervical non-HPV16/18 infection, as risk factors associated with persistence of nonvaccine HPV types will become increasingly relevant in the setting of HPV vaccination. Methods We performed an analysis in 2039 AS04-HPV16/18–vaccinated women enrolled in a phase II/III trial in China, who were HPV DNA negative at month 0 and 6 and had at least 1 subsequent follow-up visit. Vaginal infections were detected in liquid-based cytology according to the diagnostic criteria of the Bethesda System. Associations between vaginal infections and incident and 6-month persistent non-HPV16/18 infections in the cervix were evaluated using generalized estimating equations, adjusting for the age at initial vaccination, as well as HPV types in the persistence analysis. Results Study visits with any vaginal infection had a statistically significant increased risk of incident non-HPV16/18 infection compared to those without vaginal infections (odds ratio [OR], 1.44 [95% confidence interval {CI}, 1.09–1.92]). However, vaginal infections were not associated with 6-month persistent non-HPV16/18 infection (OR, 1.02 [95% CI, .62–1.69]). Conclusions Our study suggests that common vaginal infections are not associated with persistence of non-HPV16/18 infection among HPV16/18-vaccinated women.


2017 ◽  
Vol 7 (1) ◽  
pp. 647-658 ◽  
Author(s):  
Brijesh Sathian ◽  
MG Ramesh Babu ◽  
Edwin R Van Teijlingen ◽  
Indrajit Banerjee ◽  
Bedanta Roy ◽  
...  

Background: The Human Papillomavirus (HPV) is strongly associated with cervical and other cancers. In women, cervical cancer is the third most common cancer. HPV infection can be largely prevented through vaccination of (adolescent) girls. At the same time, Nepal is a low-income country experiencing a cultural change in attitudes towards sex and sexual behaviour. However, in the adolescent population knowledge about HPV, factors associated with an increased risk of HPV and the existence of the vaccination is often low.Materials and Methods: This was a cross-sectional study with female students enrolled in health and non-health science courses in Pokhara, Nepal. The questionnaire included demographic details, knowledge and attitude questions related to HPV, associated risk behaviour and its vaccination. Descriptive statistics, including Chi-Square test, were used to identify statistically significant relationships. Ethical approval was granted by the relevant authority in Nepal.Results: Hindu religion (75.0 %; 95% CI: 70.9, 78.6) and Newari caste (75.5%; CI: 61.1, 86.7) were more aware about HPV, HPV vaccination. Hindus religion (55.6%; 95% CI: 51.2, 60.0) and Dalit caste (61.6%, 95% CI: 53.3, 69.4) more willing to be vaccinated than other religions and other castes, respectively. Not unsurprisingly, students on health-related courses had a greater awareness of HPV, HPV vaccination and were more willing to be vaccinated than students on other courses. Similar patterns of association arose for knowledge related to those sexually active at an early age; HPV risk and multiple sex partners; and fact that condoms cannot fully prevent the transmission of HPV.Conclusion: Knowledge about the link between HPV and (a) early sexual initiation, (b) having multiple sexual partners, and (c) the limited protection of condoms and other birth control measures was poor in our study compared to similar research conducted in other parts of the world. One key implication is the need for education campaigns in Nepal to educate young women and their parents about HPV, its risk factors and the benefits of vaccination.


Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 776
Author(s):  
Tomasz Milecki ◽  
Maciej Michalak ◽  
Jakub Milecki ◽  
Michał Michalak ◽  
Radosław Kadziszewski ◽  
...  

Introduction: Human papillomavirus (HPV) is associated with six types of cancer in men and women. A vaccine against HPV, preferably administered before initial sexual intercourse, has been proven to be highly effective in preventing these cancers. An effective healthcare provider recommendation has significant influence on HPV vaccine uptake; therefore, it is critical that medical students receive comprehensive training in this area. Aim: The aim of the study was to assess the knowledge of medical students regarding Human Papillomavirus’s (HPV) ways of transmission, risk of cancer development, and vaccination against HPV. This study also investigated factors among medical students that would affect their intention to recommend HPV vaccination to others. Materials and Methods: The study was conducted among 1061 (678 women and 383 men) medical students who filled in our questionnaire. The medical students were divided into two subgroups: (1) pre-clinical medical students (MS pre-clinical; first-to third-year students; n = 683) and (2) clinical medical students (MS clinical; fourth-to six-year students; n = 378). Results: A total259 (24.41%) of the 1061 medical students were vaccinated against HPV. We found a significant improvement in the general level of knowledge in the later years of education (4–6) compared to the early years of education (1–3). However, it was demonstrated that, despite medical education advancements, there are still significant gaps of knowledge about the relationship between HPV infection and cancers other than cervical cancer, as well as in relation to the routes by which HPV is transmitted. Medical students’ intentions to recommend HPV vaccine to others were related to their own HPV-related knowledge and their own vaccination status. Conclusion: Medical students have gaps of knowledge regarding particular issues and aspects of HPV. It is necessary to further educate medical students in the field of prevention and in the treatment of lesions caused by HPV infection. Medical students’ intention to recommend the HPV vaccine can be improved by including them and members of their families in the HPV vaccination program.


2021 ◽  
pp. 1-12
Author(s):  
L. Díaz de León-Martínez ◽  
C.M. López-Mendoza ◽  
Y. Terán-Figueroa ◽  
R. Flores-Ramírez ◽  
F. Díaz-Barriga ◽  
...  

Cervical cancer (CC) is one of the most serious threats to the lives of women; co-factors in addition to oncogenic human papillomavirus (HPV) infection may be important in causing CC. Women in Mexico are exposed to dietary aflatoxin B1, a potent carcinogen, which may act as a co-factor, in inducing progression to CC. Scarce studies are addressing environmental risks associated with the development of CC, thus the study aimed to establish a relationship between the presence of AFB1 and the detection of human papillomavirus in the genome of Mexican women. Forty samples from cervical tissue of women infected with HPV were obtained; positive results regarding the HPV type (16 and/or 18) were found in 92.5% women and the presence of AFB1-DNA adducts were detected in 77.5% of the same positive HPV samples. Detection of AFB1-DNA adducts and genomic concentrations were correlated with the detection of two oncogenic types of HPV 16 and 18. AFB1-DNA positivity and higher genomic concentrations of AFB1-DNA adducts were correlated with an increased risk of oncogenic detection of HPV in cervical samples from women in Mexico. As a secondary objective, a hypothetical interaction of the adducts with the NRF2 pathway has been proposed, therefore activation of p62 and in turn E6 and E7 (HPV proteins) would inhibit the formation of autophagosomes, which would result in a presence or recurrence of CC.


2018 ◽  
Vol 94 (6) ◽  
pp. 434-442 ◽  
Author(s):  
Xiaomeng Ma ◽  
Qian Wang ◽  
Jason J Ong ◽  
Christopher K Fairley ◽  
Shu Su ◽  
...  

ObjectiveHuman papillomavirus (HPV) infection causes multiple cancers in both women and men. In China, both HPV vaccination and cervical cancer screening coverages are low. We aim to investigate the temporal and geographical trends of HPV DNA prevalence in heterosexual men, women, men who have sex with men (MSM) and people living with HIV (PLHIV) in China.MethodsWe conducted a systematic review, collecting publications in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Data from January 2000 to May 2017. A total of 247 studies were selected for this meta-analysis to estimate pooled HPV prevalence, incidence of cervical cancer and risk of infection for subgroups. Meta-regression was applied to identify contributing factors to prevalence heterogeneities.ResultsThe national HPV prevalence was 15.6% (95% CI (14.4% to 16.9%)) in women with normal cervical cytology, and Central China had the highest prevalence (20.5% (15.2% to 25.8%)). HPV prevalence in heterosexual men (14.5% (11.3% to 17.7%)) was comparable with that of women (OR=1.09 (0.98 to 1.17)), but HPV prevalence in MSM (59.9% (52.2% to 67.6%)) was significantly higher than that in heterosexual men (OR=8.81 (8.01 to 9.69)). HIV-positive women (45.0% (38.4% to 51.6%)) and HIV-positive MSM (87.5% (82.3% to 90.9%)) had 4.67 (3.61 to 6.03) and 6.46 (5.20 to 8.02) times higher risk of HPV infection than their HIV negative counterparts.ConclusionHPV infection is prevalent in China, particularly in Central China, in comparison with the global level and neighbouring countries. Targeted HPV vaccination for women, MSM and PLHIV and scale-up of cervical screening for women are priorities in curbing the HPV epidemic in China.


2021 ◽  
Vol 6 (4) ◽  
pp. 714-722
Author(s):  
Sajeda Khatun ◽  
Ashees Kumar Saha ◽  
Irtiza Ahmed Chowdhury ◽  
Arifa Sultana ◽  
Mst Wazeda Begum ◽  
...  

Human papillomavirus (HPV) infection is one of the causes of cervical cancer which is preventable. The study was a cross-sectional study with the objective was to determine the Human papillomavirus (HPV) vaccination coverage among working women. A total 236 educated working women were selected purposively from different working places in Dhaka city. A pretested semi- structured questionnaire was used for data collection. The knowledge was assessed by using modified Blooms cut off points which was developed with cervical cancer and vaccine knowledge related questions. The study result revealed that among 236 working women 71.2% knew about the risk factor of cervical cancer. It was found that 92.8% knew about the way of prevention of cervical cancer respectively. The overall knowledge on cervical cancer and vaccine was found to be having good knowledge 21.2%, satisfactory knowledge 41.9% and poor knowledge 36.9%. Out of the total working women only 5.1% had HPV vaccination coverage. Reason behind non vaccinations, 50% mentioned had no knowledge about vaccine, 35.3% mentioned can’t decide and 8.9% mentioned high cost of vaccine. Significant association has been observed in between vaccination coverage with over all knowledge of cervical cancer (p value .04). It may be concluded that HPV vaccination coverage is very low which needs awareness program on this issues through mass media, educational session, counseling and so on to reduce human papillomavirus associated cancers as well as economic burden. Asian J. Med. Biol. Res. December 2020, 6(4): 714-722


GYNECOLOGY ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 125-130
Author(s):  
Yuliya E. Dobrokhotova ◽  
Ekaterina I. Borovkova

The article provides a literature review on the prevention of cervical cancer by human papillomavirus (HPV) vaccination. Currently, 3 vaccines are available: the 4-valent vaccine against HPV types 6, 11, 16 and 18, the 9-valent vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 and the bivalent vaccine against HPV types 16 and 18. Vaccination provides protection for women and men against infection with HPV and further development of HPV-associated diseases. Following immunization, seroconversion develops in 93-100% of women and in 99-100% of men and is effective in preventing incident and persistent HPV infection as well as cervical intraepithelial neoplasia. HPV immunization is ineffective in treating an existing HPV infection, genital warts, or anogenital intraepithelial neoplasia. HPV vaccination status does not affect recommendations for cervical cancer screening.


2020 ◽  
Author(s):  
Mohammad Farahmand ◽  
Seyed Hamidreza Monavari ◽  
Ahmad Tavakoli

Abstract Background: Homosexual men or men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviors. In this large study, a meta-analytic approach was used to systematically analyze the literature to elucidate the prevalence and genotype distribution of anal, penile, oral, and urethral HPV infection among MSM in the world.Methods: To carry out this systematic review, five electronic databases were searched for relevant studies published from January 2012 through to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalences were calculated for each anatomical region using random-effect model weighted by the inverse variance method. Subgroup analyses were performed to identify the probable sources of heterogeneity. The meta-analysis was performed using the “Metaprop” function in the R package Meta.Results: The overall pooled prevalence of anal, penile, oral, and urethral HPV infection among MSM were 78.11 % (95% CI: 75.50%-80.52%), 36.26% (95% CI: 29.13%–44.05%), 17.33% (95% CI: 13.65%–21.75%), and 15.40% (95% CI: 7.86%–27.97%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis, and oral cavity was HPV-16 (20.32%, 4.96%, and 3.16%, respectively). Conclusion: HPV infection is on the dramatic rise in MSM because of high-risk sexual behaviors, strongly suggesting the increased risk of developing HPV-related diseases and malignancies in this population. Among different sexual orientations, male homosexuality is associated with the highest risk of acquiring sexually transmitted infections.


Sexual Health ◽  
2010 ◽  
Vol 7 (3) ◽  
pp. 394 ◽  
Author(s):  
Carol Chelimo ◽  
Trecia A. Wouldes ◽  
Linda D. Cameron

Two-hundred undergraduate students completed an anonymous questionnaire after viewing a human papillomavirus (HPV) vaccine television commercial. Eight-four percent of participants would accept a free HPV vaccine, whereas 47% were unconcerned about future personal HPV infection risk. Males were less likely to accept a free HPV vaccine and to be concerned about future personal HPV infection risk. Perceived HPV vaccine effectiveness was significantly greater among participants who had previously heard of the vaccine and who knew that HPV is sexually transmitted. More education on the role of sexual behavioural characteristics of both males and females in HPV transmission is necessary to promote awareness and concern of personal HPV infection risk and acceptance of HPV vaccination.


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