Treatment Of HPV-related Disease Research Articles

Influential factors and willingness to advocate for HPV vaccination among male nursing interns in China

BackgroundHuman papillomavirus (HPV) infection significantly contributes to the global cancer burden. Understanding the factors influencing male clinical interns’ willingness to promote HPV vaccination is crucial for developing effective public health strategies in China.MethodsThis study employed a stratified random sampling method to select 1,980 male clinical interns from five provinces in China between January and March 2024. Data were collected on participants’ demographic characteristics, HPV-related clinical experience, and knowledge. The Theory of Planned Behavior framework, encompassing attitudes, subjective norms, and perceived behavioral control, was used to examine factors influencing the willingness to promote the HPV vaccine. Logistic regression analyses were conducted to identify factors associated with the willingness to promote the HPV vaccine.ResultsAmong the respondents, 72.29% were willing to encourage others to receive the HPV vaccine. Significant factors influencing this willingness included older age (OR = 3.065, P ≤ 0.001), higher monthly household income (OR = 1.449, P = 0.025), participation in the diagnosis and treatment of HPV-related diseases (OR = 3.458, P ≤ 0.001), positive attitude towards the vaccine (OR = 13.503, P = 0.004), and strong perceived behavioral control (OR = 2.364, P = 0.006).ConclusionThis study highlights the critical role of practical experience and targeted education in promoting HPV vaccination among male clinical interns in China. Enhancing the training and education of this group is essential for improving HPV vaccine advocacy and supporting public health efforts to reduce HPV-related diseases.

The polymorphism analysis and therapy vaccine target epitopes screening of HPV-35 E6 E7 among the threaten α-9 HPV in Sichuan area

High-risk human papilloma virus (HR-HPV) persistent infection is closely associated with the development of cervical cancer and squamous intraepithelial lesion (SIL).The α-9 HPVs, which is predominantly composed of HR-HPV types, account for 75% of HR-HPV infection in Sichuan. The oncoproteins E6 and E7 of HPV play a crucial role in tumor initiation and progression. Notably, HPV-35 is the only HR-HPV type within the α-9 genus that is not included in the nine-valent HPV prophylactic vaccine. Cervical cell samples obtained from Sichuan were collected for HPV detection and genotyping. Among the 406 HPV-positive samples, 31 HPV-35 were detected, 24 HPV-35 E6 and 26 E7 were successfully amplified and sequenced, five nucleotide mutations in E6 and three in E7 were detected, T232C, T434G of E6 (W78R, I145R) and C67T, G84T of E7 (H23Y, L28F) were non-synonymy mutation. PAML 4.8 server was used to detect positive selection sites of HPV-35 E6, E7, and E6 is W78R. Phyre2 were used to predict and analyze protein structures, W78R made influences on protein structure. IEDB were used to screen epitopes vaccine target for HPV-35 affection therapy, and 5 HPV-35 E6 and 3 HPV-35 E7 most potential epitopes were obtained, the most potential peptides for therapy vaccine design were 79-91YRYSVYGETLEKQ, 45-60FACYDLCIVREGQPY, 124-135RFHNIGGRWTGR of E6; 3-19GEITTLQDYVLDLEPEA, 38-47TIDGPAGQAK, 70-88VQSTHIDIRKLEDLLMGTF of E7 and W78R mainly decreased the epitopes affinity.Conclusions Amino acid substitution in the positive selection sites of HPV-35 E6 and E7 genes have been found to influence protein structure and to decrease the overall affinity of antigen epitopes. This observation aligns with the evolutionary significance of positive selection site, which may confer advantages to the virus by making infected cells more challenging for the immune system to detect, thereby enhancing HPV’s adaptability to the host environment. The polymorphism analysis of HPV-35 E6, E7 contributes to the enrichment of α-9 HPV data in Sichuan China, which is instrumental in improving the effectiveness of clinical detection. Furthermore, these findings provide a relevant theoretical foundation for the prevention and treatment of HPV-related diseases.

The polymorphism analysis and epitope predicted of Alphapapillomavirus 9 E6 in Sichuan, China

BackgroundThe Alphapapillomavirus 9 (α-9 HPV) is a member of the Alphapapillomavirus genus and Papillomaviridae family. These viruses are almost all carcinogenic HPV, which is closely related to 75% of invasive cervical cancer worldwide, and has a high prevalence in Sichuan. The carcinogenic function is mainly realized by its E6 oncoprotein.MethodsCell samples were collected by cervical scraped for HPV detecting and typing. HPV-16, HPV-31, HPV-33, HPV-52, HPV-58 5 α-9 genus HPV subtype positive samples were selected, their E6 gene was sequenced and analyzed. The positive selection sites of HPV E6 genes were estimated by PAML 4.8 server. The secondary and tertiary structure of E6 protein were predicted by PSIPred and Swiss-model. The T-cell antigen epitopes of E6 protein were predicted by IEDB.Resultsα-9 HPV has a high prevalence in Sichuan, China. From 2012 to 2017, 18,067 cell cervical samples were collected, and 3135 were detected with α-9 HPV infection. Among which, 250 cases HPV-16 E6, 96 cases HPV-31 E6, 216 cases HPV-33 E6, 288 cases HPV-52 E6 and 405 cases HPV-58 E6 were successfully amplified, 17, 6, 6, 13, and 4 non-synonymous nucleotide mutations were respectively detected in HPV-16, 31, 33, 52, and 58 E6, 7 positive selection sites of α-9 HPV E6 were selected out (D32E of HPV-16 E6, K35N, K93N and R145I of HPV-33 E6, K93R of HPV-52 E6, K93N and R145K of HPV-58 E6). The structure and antigen epitopes of E6 protein with amino acid substitution differ from those of wild-type E6 protein, especially for the mutation located in the E6 positive selection site.ConclusionsHPV E6 nucleotide non-synonymous mutation in the positive selection site influence the protein structure and decrease the antigen epitopes affinity of the E6 protein overall, making it more difficult for the HPV-infected cells to be detected by the immune system, and enhancing the HPV adaptability to the environment. Mutations influence the validity of HPV clinical diagnostic probes, the polymorphism analysis of α-9 HPV E6 enrich the data of HR-risk HPV in Sichuan China, and the detection probes designed with the polymorphism data in mind can improve the efficiency of clinical detection; Mutations influence epitopes affinity, the association of E6 polymorphism and epitope affinity can improve the design of therapeutic vaccine with good immunity and high generality antigen epitope; The above study all provide a good theoretical basis for the prevention and treatment of HPV-related diseases.

Insights into the Role of Innate Immunity in Cervicovaginal Papillomavirus Infection from Studies Using Gene-Deficient Mice.

We demonstrate that female C57BL/6J mice are susceptible to a transient lower genital tract infection with MmuPV1 mouse papillomavirus and display focal histopathological abnormalities resembling those of human papillomavirus (HPV) infection. We took advantage of strains of genetically deficient mice to study in vivo the role of innate immune signaling in the control of papillomavirus. At 4 months, we sacrificed MmuPV1-infected mice and measured viral 757/3139 spliced transcripts by TaqMan reverse transcription-PCR (RT-PCR), localization of infection by RNAscope in situ hybridization, and histopathological abnormities by hematoxylin and eosin (H&E) staining. Among mice deficient in receptors for pathogen-associated molecular patterns, MyD88-/- and STING-/- mice had 1,350 and 80 copies of spliced transcripts/μg RNA, respectively, while no viral expression was detected in MAVS-/- and Ripk2-/- mice. Mice deficient in an adaptor molecule, STAT1-/-, for interferon signaling had 46,000 copies/μg RNA. Among mice with targeted deficiencies in the inflammatory response, interleukin-1 receptor knockout (IL-1R-/-) and caspase-1-/- mice had 350 and 30 copies/μg RNA, respectively. Among mice deficient in chemokine receptors, CCR6-/- mice had 120 copies/μg RNA, while CXCR2-/- and CXCR3-/- mice were negative. RNAscope confirmed focal infection in MyD88-/-, STAT1-/-, and CCR6-/- mice but was negative for other gene-deficient mice. Histological abnormalities were seen only in the latter mice. Our findings and the literature support a working model of innate immunity to papillomaviruses involving the activation of a MyD88-dependent pathway and IL-1 receptor signaling, control of viral replication by interferon-stimulated genes, and clearance of virus-transformed dysplastic cells by the action of the CCR6/CCL20 axis.IMPORTANCE Papillomaviruses infect stratified squamous epithelia, and the viral life cycle is linked to epithelial differentiation. Additionally, changes occur in viral and host gene expression, and immune cells are activated to modulate the infectious process. In vitro studies with keratinocytes cannot fully model the complex viral and host responses and do not reflect the contribution of local and migrating immune cells. We show that female C57BL/6J mice are susceptible to a transient papillomavirus cervicovaginal infection, and mice deficient in select genes involved in innate immune responses are susceptible to persistent infection with variable manifestations of histopathological abnormalities. The results of our studies support a working model of innate immunity to papillomaviruses, and the model provides a framework for more in-depth studies. A better understanding of mechanisms of early viral clearance and the development of approaches to induce clearance will be important for cancer prevention and the treatment of HPV-related diseases.

Abstract A86: Challenges and opportunities for increasing the rates of HPV vaccination

Abstract Purpose: The purpose of this study is to determine the association between awareness of human papillomavirus (HPV), cervical cancer, and HPV vaccine and intention to vaccinate preteens and teens against HPV. Background: Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, and results in 14 million new cases each year. Around 50% of new HPV infections occur among persons aged 15-24 years old. Cervical cancer is primarily attributable to HPV, and the yearly cost of cervical cancer screening as well as treatment of HPV-related diseases is around $8 billion. In 2009, around 35,000 HPV-related cancers were reported in the United States. The level of coverage for 3 HPV vaccine doses for females aged 13-15 years was only 30% in 2011. This is far below the 80% target coverage level set by Healthy People 2020. The 2013 National Immunization Survey-Teen found that only 50% of Maryland females aged 13-17 years and only 34.2% of male adolescents reported beginning the HPV vaccine series. According to the 2013 Maryland Cancer Data, Maryland had the 25th highest cervical cancer mortality rate from 2006-2010. During these years, more black women were diagnosed with cervical cancer than White women, and their rate of cervical cancer incidence has been increasing at a rate of 4.9% more per year than white women. We investigate the relationship between HPV, cervical cancer, and HPV vaccine awareness and intention to vaccinate preteens and teens against HPV. Methods: Utilizing the principles of community-based participatory research (CBPR), the Johns Hopkins Center to Reduce Cancer Disparities, in collaboration with its Community Advisory Groups in Baltimore City and Prince George's County, developed and implemented a survey to assess the knowledge, awareness and behavioral intentions on cervical cancer, HPV and HPV vaccine. The study was approved by the Johns Hopkins School of Medicine's Institutional Review Board and implemented between March 2015 and July 2015 in Baltimore City and Prince George's County. Four hundred and three individuals recruited through community events completed the assessment. Upon completion of the assessment, participants were given feedback on their responses to address any knowledge gap and educational materials. Binary and multinomial logistic regression were used to determine the association between awareness of HPV, cervical cancer, and HPV vaccine and intention to vaccinate children between the ages of 11 and 18 years against HPV. Results: The majority of study participants were female (78%), black or African American (87%), have at least one year of college or technical school (55%) and have an annual household income of less $20,000 (38%). Awareness of the existing of HPV vaccine is significantly associated (OR=2.54, P<0.0007, CI 1.487-4.355) with the intention to vaccinate children against HPV. We also found that individuals who never heard of the HPV vaccine are significantly less likely (OR=0.394, p<0.0007, CI 0.230-0.673) to vaccinate their children against HPV than those who have heard of the vaccine. Furthermore, those who are aware of HPV are significantly more likely to know that HPV can cause cervical cancer (OR=5.25, P<0.0001, CI 3.272-8.454) and to know that HPV is transmitted through sexual contact (OR=3.66, P<0.0001, CI 2.199-6.100) compared to those who never heard of HPV. Conclusion: Awareness of HPV, cervical cancer, and HPV vaccine are significantly associated the intention to vaccinate children between the ages of 11 and 18 years against HPV. Increasing knowledge of cervical cancer and the importance of HPV vaccination among parents and caretakers of preteens and teens have the potential to increase the rates of HPV vaccination and prevent future cervical cancers. More research is needed to explore other factors that are related to HPV vaccination. Citation Format: Ahmed Elmi, Saad Tassaduq, Olive Mbah, Ashleigh DeFries, Lee Bone, Anjani Kapadia, Theron Scott, Nichole Tuite, Adrian Dobs. Challenges and opportunities for increasing the rates of HPV vaccination. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A86.

EUROGIN 2011 roadmap on prevention and treatment of HPV-related disease.

The EUROGIN 2011 roadmap reviews the current burden of human papillomavirus (HPV)-related morbidity, as well as the evidence and potential practice recommendations regarding primary and secondary prevention and treatment of cancers and other disease associated with HPV infection. HPV infection causes ~600,000 cases of cancer of the cervix, vulva, vagina, anus and oropharynx annually, as well as benign diseases such as genital warts and recurrent respiratory papillomatosis. Whereas the incidence of cervical cancer has been decreasing over recent decades, the incidence of anal and oropharyngeal carcinoma, for which there are no effective screening programs, has been rising over the last couple of decades. Randomized trials have demonstrated improved efficacy of HPV-based compared to cytology-based cervical cancer screening. Defining the best algorithms to triage HPV-positive women, age ranges and screening intervals are priorities for pooled analyses and further research, whereas feasibility questions can be addressed through screening programs. HPV vaccination will reduce the burden of cervical precancer and probably also of invasive cervical and other HPV-related disease in women. Recent trials demonstrated that prophylactic vaccination also protects against anogenital HPV infection, anogenital intraepithelial lesions and warts associated with vaccine types, in males; and anal HPV infection and anal intraepithelial neoplasia in MSM. HPV-related oropharyngeal cancer could be treated less aggressively because of better survival compared to cancers of the oropharynx unrelated to HPV. Key findings in the field of cervical cancer prevention should now be translated in cost-effective strategies, following an organized approach integrating primary and secondary prevention, according to scientific evidence but adapted to the local situation with particular attention to regions with the highest burden of disease.

Highlights of the 27th International Papillomavirus Conference and Clinical Workshop: part 3: Epidemiology and Public Health

The 27th International Papillomavirus Conference and Clinical Workshop, held in Berlin (17–22 September 2011) brought together more than 2000 scientists, clinicians and public health experts who shared new findings in the knowledge of the HPV and the prevention and treatment of HPV-related disease. In this last of three reports of the conference, the sessions and workshops dedicated to epidemiology and public health are summarized, which focused on the natural history of HPV infection, risk factors for HPV infection and HPV-associated lesions, descriptions of the current burden and trends of HPV-related cancers, HPV testing in cervical cancer screening and management of women who screen positively, prophylactic HPV vaccination, prevention of cervical cancer in low-resource countries through screening and vaccination, and the prevention and treatment of other cancers caused by HPV. The report ends with the highlights of the 6th Cochrane workshop on systematic reviews regarding prevention of HPV-related disease. The first two parts of the 27th International Papillomavirus conference on Basic Science and Applied Clinical Science were covered in the two previous issues of Future Virology.

Highlights of the 27th International Papillomavirus Conference and Clinical Workshop: Part 2: Applied Clinical Science

The 27th International Papillomavirus Conference and Clinical Workshop, held in Berlin (17–22 September 2011), brought together more than 2000 scientists, clinicians and public health experts who shared new findings in the knowledge of the HPV and the prevention and treatment of HPV-related disease. In this second of three reports of the conference, the applied clinical science sessions are summarized, which focused on immunology, new HPV tests, benign HPV infections, noncervical HPV-related disease, primary and secondary prevention of cervical cancer by HPV-based screening and prophylactic HPV vaccination and treatment of HPV-induced disease. The clinical workshops discussed possible alternative schedules of prophylactic HPV vaccination, prevention of anal cancer and anal precancer, validation of HPV genotyping assays, establishment of standards and laboratory proficiency in testing for HPV DNA and anti-HPV antibodies through the WHO LabNet, and currently heavily debated questions on the role of colposcopy in the assessment of cervical cancer precursors.

Highlights of the 27th International Papillomavirus Conference and Clinical Workshop: part 1

The 27th International Papillomavirus Conference, held in Berlin (17–22 September 2011) brought together more than 2000 scientists, clinicians and public health experts who shared new findings in the knowledge of the HPV and the prevention and treatment of HPV-related disease. In this first of three reports of the conference, the keynote lectures and the basic science sessions are summarized, which focused on the virus life cycle, the viral E and L proteins, the molecular pathways of HPV-induced carcinogenesis, the humoral and cellular immunologic responses elicited by prophylactic and therapeutic vaccines and new diagnostic tests and antiviral drugs.

The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus‐Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Sexually Active Women Aged 16–26 Years

We evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment. Phase 3 efficacy studies enrolled 17,622 women aged 16-26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6-12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received 1 dose and returned for follow-up were included. Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59-related CIN1-3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed, the estimated reduction was not statistically significant. These cross-protection results complement the vaccine's prophylactic efficacy against disease associated with HPV-6, -11, -16, and -18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings. ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.

Cidofovir Incorporation into Human Keratinocytes with Episomal HPV 16 Results in Nonselective Cytotoxicity

Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV). Surgical excision is the mainstay of treatment; however, medical therapy including cidofovir, a cytosine analog, has been investigated. Human papillomavirus does not encode a viral DNA polymerase, which is the known target of cidofovir in cytomegalovirus infections. In an effort to better understand the usefulness of cidofovir in the treatment of HPV-related disease, we tested cidofovir's ability to inhibit growth, alter gene expression, and inhibit genome replication. With the use of carbon 14-labeled cidofovir in episomal HPV 16-containing keratinocytes, there was a minimal increase in cidofovir incorporation into episomal DNA versus genomic DNA. Cidofovir decreased the copies of episomal HPV 16 in keratinocytes; however, the copies per cell returned to baseline levels once cidofovir was removed. Expression of a viral oncogene (HPV 16 E6) in transformed keratinocytes with episomal HPV 16 was not decreased by cidofovir. Cytotoxicity in head and neck squamous cell carcinoma lines exposed to cidofovir correlated with cell doubling time, and not with HPV status. Also, tonsil keratinocytes transformed with episomal HPV 16 did not exhibit greater cidofovir-mediated toxicity than did telomerase-transformed keratinocytes. These findings suggest that any potential in vivo benefit of cidofovir therapy results from non-viral-specific cell toxicity at the site of application.

Chemoprevention and vaccines: a review of the nonsurgical options for the treatment of cervical dysplasia

Human papillomavirus (HPV)-related disease is a significant health problem in the United States and throughout the world, especially in developing countries. Standard treatment to date has been surgical excision, but we ask the question “For what other clinically evident, virally mediated disease is the standard of treatment surgery?” The authors performed a systematic literature review and selected articles most relevant to the topic. This article reviews prevention, chemoprevention, and vaccine trials for the prevention and treatment of HPV-related disease of the genital tract. Significant advances have been made in the last decade, and the future holds promise for effective nonsurgical options for the patients with cervical dysplasia and other HPV-associated diseases.

Screening and Treatment of HPV-Related Diseases in Gynecologic Practice

Cervical cancer screening through Pap smears and colposcopy remains the standard model for most early cancer detection programs. The natural history of HPV infection allows for detection and treatment of precancerous changes, which in turn allows for reduction in morbidity and mortality from disease. A better understanding of low-risk and high-risk lesions, as well as low-risk and high-risk HPV subgroups, has also allowed for new strategies in triage and utilization of health care resources.