Prophylactic HPV Vaccines Research Articles

The Relationship between Oral Squamous Cell Carcinoma and Human Papillomavirus: A Meta-Analysis of a Chinese Population (1994–2011)

BackgroundPrevious studies indicated that oral squamous cell carcinomas (OSCC) might be related to human papilloma virus (HPV) infection. However, up to now, there still lacks a large sample study to analyze the relationship between OSCC in a Chinese population and oral HPV infection. In the present study, we used a meta-analysis to evaluate the relationship of OSCC with HPV infection in a Chinese population.MethodsThe reports on HPV and OSCC in a Chinese population published between January, 1994, and September, 2011 were retrieved via CNKI/WANFANG/OVID/MEDLINE databases. According to the inclusion criteria, we selected 18 eligible case-control studies. After testing the heterogeneity of the studies by the Cochran Q test, the meta-analyses for HPV and HPV16 were performed using the fixed effects model.ResultsThe overall positive rates of HPV and HPV16 in OSCC were 58.0% (354/610; 95% confidence interval [CI], 54.1–61.9) and 47.47% (169/356; 95% CI: 42.3–52.7), respectively; which were significantly higher than those in normal controls 10.44% (26/249; 95% CI: 7.2–14.7) and 7.1% (13/182; 95% CI: 4.2–11.8). Quantitative meta-analysis revealed that, compared with normal controls, the combined odds ratios of OSCC with HPV or HPV16 infection were 12.7 (95% CI: 8.0–20.0) and 9.0 (95% CI: 5.1–15.6), respectively. Both Begg's test and funnel plots revealed that no publication bias was found in this present study (P>0.05).ConclusionsHigh incidences of HPV infection (mainly involving HPV16) were found in the samples of Chinese OSCC. For the Chinese population, HPV infection elevates the risk of OSCC tumorigenesis. Prophylactic HPV-vaccination may reduce the burden of HPV-related OSCC in China.

Abstract 5704: Curcumin-folate conjugate for increased bioavailability and targeted delivery of curcumin to cancer cells

Abstract Specific types of high risk Human Papillomavirus (HR-HPV) types, particularly the HPV type 16 and HPV 18 are known to cause cervical cancer. The expression of two viral oncogenes E6 and E7 responsible for tumorigenic transformation, is mainly dependent on specific host-cell transcription factor, Activator Protein 1 (AP-1) which acts as a signaling epicenter for cervical cancer. Although recently two prophylactic HPV vaccines have been developed, there is no therapeutic molecule available for the treatment of cervical lesions. We demonstrate that Curcumin (Diferuloylmethane), a yellow pigment, used in traditional medicines and present in the dietary spice turmeric (Curcuma longa), can selectively down regulate HPV 18 transcription as well as AP-1 binding activity. Curcumin can also reverse the expression dynamics of c-fos and fra-1 in tumorigenic HeLa cells by mimicking their expression pattern in normal cells. But the bioavailability of curcumin is extremely poor due to its hydrophobicity, rapid metabolism and lack of specificity in targeting cancer cells. Therefore, a folic acid-curcumin conjugate for mutation has been developed by attaching one molecule of curcumin with two molecules of folic acid (Cur-2FA) to make curcumin hydrophilic, enhance its bioavailability and to target only cancer cells which specifically express high level of folate receptors. The effect of both native curcumin and Cur-2FA on HPV and AP-1 has been analyzed in HPV positive cervical cancer and HPV negative breast cancer cell lines, by band shift assay, confocal microscopy, flow cytometry and western blotting including their cytotoxic potential and targeted cellular uptake of curcumin. In comparison to native curcumin, curcumin-2FA has been found to be atleast two times more effective in inducing down regulation of HPV transcription, AP-1 activity and expression of its components particularly c-fos and fra-1. Curcumin-2FA was found to be more potent than curcumin in inducing apoptosis, inhibits tumor cell proliferation and Cur-2FA conjugate was specifically taken up by cancer cells. In mice, curcumin-2FA was more bioavailable and had a longer half-life than curcumin. We demonstrate that this nontoxic low molecular weight curcumin-2Folic acid conjugate formulation specifically targets cancer cells which overexpress high affinity folate receptor and enhanced cellular uptake facilitating increased bioavailability and targeted delivery to cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5704. doi:1538-7445.AM2012-5704

Abstract SY12-01: HPV vaccines: The opportunity to prevent multiple cancers

Abstract SY12-01: HPV vaccines: The opportunity to prevent multiple cancers

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.

Increasing fear of adverse effects drops intention to vaccinate after the introduction of prophylactic HPV vaccine

The purpose of this study was (1) to explore for socio-demographic factors that could potentially affect the intention of women to vaccinate themselves, their 13-year-old daughter and their 13-year-old son against HPV, and (2) to investigate the main reasons for declining vaccination. A structured questionnaire was used in participants of the project (N = 5,249). Logistic regression analysis was applied in order to examine the correlation between vaccine acceptability and a list of potential predictors. In women declining vaccination, the reported reasons for decline were analyzed. Residence in rural areas and low to medium tiers of family income were the most constant factors in favor of intention to vaccinate. Receiving information from a healthcare professional was found to positively affect vaccine acceptability for the woman herself, but it did not affect her intention to vaccinate her daughter or her son. The acceptance rates decreased significantly after the vaccine became available, both for the women themselves and for their daughters or sons. During the same year, a shift was noted in the reason for declining vaccination; the self-perception of insufficient knowledge significantly decreased and the fear of adverse effects significantly increased in all three cases. Apart from demographic factors which may favor or disfavor vaccine acceptability, the intention to vaccinate decreased significantly and the proportion of women rejecting vaccination for safety concerns increased significantly after the introduction of the vaccine, coinciding with isolated cases of negative publicity and highlighting the potential of misinformation by the media.

HPVワクチン

Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.

Vaccine Strategies against Human Papillomavirus: A Discussion Focused on Developing Countries

Cervical cancer is the second most common form of cancer among women, and responsible for 274,000 deaths each year, most of which occur in developing countries. Persistent infection with high-risk human papillomavirus (HR-HPV) is an essential factor in the development of cervical cancer and also a contributory factor in other types of cancer. The current prophylactic HPV vaccines provide protection against the -16 and -18 genotypes which are most commonly associated with cervical cancer worldwide. However, the increased costs of these vaccines inhibit their implementation in developing countries, affecting their viability. Moreover, a therapeutic vaccine is needed for women who are already infected by HPV and/or affected by HPV-related cancer. A number of innovative approaches to combat and treat HPV infection are currently being studied and some of these will be consider in this work, together with the development of new vaccines, especially in seriously affected areas located in developing countries. At the same time, there will be a discussion of the issues involved in carrying out effective HPV vaccination programs; these will take account of financial constraints, the lack of adequate infrastructure and the competing priorities, that are found in the surrounding social context of the developing countries.

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.

Human papillomavirus infection among young adolescents in India: Impact of vaccination

High-risk human papillomaviruses (HR-HPVs) are the causative agents of cervical cancer and prophylactic HPV vaccination has been recommended for adolescents but no data are available on the prevalence of HPV infection among adolescents in India. Self-collected midstream urine samples from 940 healthy school children, aged 8-17 years, from 12 different schools in and around Noida and Delhi, India, were collected for HPV detection by PCR. Of 458 girls, 15 (3.2%) were positive for HPV and 10 (66.6%) were positive for high-risk human papillomavirus (HR-HPV) type16 and 2 (13.3%) for HPV 18. Of 342 boys, 7 (2.1%) were HPV positive, of which 5 (71.4%) had HPV type 6 but interestingly, none were positive for HR-HPV types 16 or 18. Among HPV positive girls, 13 (66.6%) were >13 years and the rest were <13 years (P = 0.004), while all seven HPV positive boys were >13 years (P = 0.007). The majority of HPV positive adolescents (80-86%) belonged to the Hindu and related communities, whereas only about 14-20% belonged to the Muslim community. A significant association (P < 0.001) was observed between the parent's education and the awareness of cervical cancer, which was significantly higher among adolescent girls from India, thereby exerting an immense psychosocial impact on vaccination programs. A lower prevalence of HR-HPV infection among adolescent girls will have significant positive effect on HPV vaccination and cancer control programs in India where education and awareness should go hand in hand.

Human papillomavirus genotype distribution in cervical cancer cases in Spain. Implications for prevention

ObjectiveHuman papillomavirus (HPV) genotype distribution in invasive cervical cancer (ICC) is critical to guide the introduction and to assess the impact of HPV prophylactic vaccines. This study aims to provide specific information for Spain. Methods1043 histological confirmed ICC cases diagnosed from 1940 to 2007 from six Spanish regions were assembled. HPV DNA detection was performed by SPF10 broad-spectrum PCR followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA25) (version 1). ResultsOf 1043 ICC cases, 904 were HPV DNA positive (adjusted prevalence: 89.1%). The eight most common types, in decreasing order, were HPV 16, 18, 33, 31, 45, 35, 52 and 56, accounting for more than 90% of cases. HPV 16 and 18 contributed to 72.4% of all HPV positive ICC cases. In cervical adenocarcinomas, this contribution increased up to 94%. HPV 16 and 18 relative contributions showed a stable pattern over the 60year study period. HPV 45, 18 and 16-positive ICC cases presented at younger ages than cases with other HPV types (adjusted mean age: 43.8, 45.2, 52.6 and 57.7years, respectively). ConclusionsHPV 16 and 18 accounted together for a 72.4% of positive cases, with no statistically significant changes in their relative contributions over the last decades. In 94% of cervical adenocarcinomas we identified at least one of the two HPV types included in the current vaccines (HPV 16/18). Results suggest a major impact of HPV vaccines on reduction of ICC burden in Spain in the HPV vaccinated cohorts.

Évaluation de la couverture vaccinale du vaccin anti-hpv : résultats d’une enquête auprès des lycéennes et étudiantes de la région PACA

To assess HPV prophylactic vaccine coverage among French high school and university students as well as their level of education about this vaccine.An anonymous survey was conducted among 2500 high school and university students from the area of Marseilles, France, from December 2009 to April 2010.A total of 2018 questionnaires were collected (80.7% participation rate). Mean age of participants was 20 years (range, 15-45 years). Only 671 (35.4%) participants reported having been vaccinated against HPV, of whom 510 (73.4%) had completed the three injections scheme. Practice of cytological cervical cancer screening was not significantly influenced by vaccination status. Thus, 578 (45.2%) participants who had not been vaccinated already had had a cervical cytology performed, versus 295 (43.3%) vaccinated ones (P=0.445). Among those not being vaccinated, 671 (49.8%) fulfilled criteria for a catch-up vaccination, of whom only 325 (48.4%) agreed for such a catch-up. Main reasons given for refusal for a catch-up vaccination were the lack of information about HPV vaccine and fear of side effects. In total, 1722 (90%) considered themselves as educated about the HPV vaccine. Source of education was attributed to doctors and media by 54.4% and 53.7% of participants, respectively. Educational role attributed to school and university was poor (3.4%).Despite apparent satisfactory level of education, HPV prophylactic vaccine coverage among high school and university students appears to be insufficient.

Construction and characterisation of a recombinant fowlpox virus that expresses the human papilloma virus L1 protein

BackgroundHuman papilloma virus (HPV)-16 is the most prevalent high-risk mucosal genotype. Virus-like-particle (VLP)-based immunogens developed recently have proven to be successful as prophylactic HPV vaccines, but are still too expensive for developing countries. Although vaccinia viruses expressing the HPV-16 L1 protein (HPV-L1) have been studied, fowlpox-based recombinants represent efficient and safer vectors for immunocompromised hosts due to their ability to elicit a complete immune response and their natural host-range restriction to avian species.MethodsA new fowlpox virus recombinant encoding HPV-L1 (FPL1) was engineered and evaluated for the correct expression of HPV-L1 in vitro, using RT-PCR, immunoprecipitation, Western blotting, electron microscopy, immunofluorescence, and real-time PCR assays.ResultsThe FPL1 recombinant correctly expresses HPV-L1 in mammalian cells, which are non-permissive for the replication of this vector.ConclusionThis FPL1 recombinant represents an appropriate immunogen for expression of HPV-L1 in human cells. The final aim is to develop a safe, immunogenic, and less expensive prophylactic vaccine against HPV.

New Approaches to Immunotherapy for HPV Associated Cancers

Cervical cancer is the second most common cancer of women worldwide and is the first cancer shown to be entirely induced by a virus, the human papillomavirus (HPV, major oncogenic genotypes HPV-16 and -18). Two recently developed prophylactic cervical cancer vaccines, using virus-like particles (VLP) technology, have the potential to prevent a large proportion of cervical cancer associated with HPV infection and to ensure long-term protection. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and do not prevent their progression to HPV-associated malignancy. In animal models, therapeutic vaccines for persisting HPV infection can eliminate transplantable tumors expressing HPV antigens, but are of limited efficacy in inducing rejection of skin grafts expressing the same antigens. In humans, clinical trials have reported successful immunotherapy of HPV lesions, providing hope and further interest. This review discusses possible new approaches to immunotherapy for HPV associated cancer, based on recent advances in our knowledge of the immunobiology of HPV infection, of epithelial immunology and of immunoregulation, with a brief overview on previous and current HPV vaccine clinical trials.

S12.3 What is the latest data from the 2 commercially available prophylactic cervical cancer vaccines?

Since 2007 two prophylactic HPV vaccines (a bivalent incorporating VLPs 16 and 18, plus a quadrivalent vaccine with VLPs 16, 18, 6, 11) have been licensed for use. This was...

S14.2 A study of African American and Latina women and human papillomavirus: lessons learnt

BackgroundAfrican American and Latina women in the United States suffer from sexually transmitted infections at higher rates than white women. It is particularly important to prevent HPV in these groups...

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the immunogenicity, clinical efficacy, and safety of prophylactic HPV vaccines in females. The assessment of clinical efficacy will address protection against HPV infection (for homologous and heterologous HPV types), against re-infection, against cervical cancer and its precursors (high-grade CIN (grade 2 or grade 3), adenocarcinoma in situ) in women previously not exposed to HPV infection (negative at enrolment for both HPV DNA and antibodies against the vaccine HPV types). We will assess clinical effectiveness by evaluating outcomes in all women, irrespective of the HPV DNA or serology status at enrolment. Evaluation by fine age and time since sexual debut categories is also planned.

High-risk human papillomavirus in non-melanoma skin lesions from renal allograft recipients and immunocompetent patients

Background:High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention.Methods:High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16INK4a, a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically.Results:The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16INK4a expression in most SCC (P<0.001) and basal cell cancers (P=0.02), while almost all SCC in situ were p16INK4a positive irrespective of HR-HPV presence (P=0.66). Diffuse p16INK4a expression was associated with lack of pRB expression (P=0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence.Conclusion:High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16INK4a expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions.

Efficacy and Safety of Prophylactic Vaccines against Cervical HPV Infection and Diseases among Women: A Systematic Review &amp; Meta-Analysis

BackgroundWe conducted a systematic review and meta-analysis to assess efficacy and safety of prophylactic HPV vaccines against cervical cancer precursor events in women.MethodsRandomized-controlled trials of HPV vaccines were identified from MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts and references of identified studies, and assessed by two independent reviewers. Efficacy data were synthesized using fixed-effect models, and evaluated for heterogeneity using I2 statistic.ResultsSeven unique trials enrolling 44,142 females were included. The fixed-effect Relative Risk (RR) and 95% confidence intervals were 0.04 (0.01-0.11) and 0.10 (0.03-0.38) for HPV-16 and HPV 18-related CIN2+ in the per-protocol populations (PPP). The corresponding RR was 0.47 (0.36-0.61) and 0.16 (0.08-0.34) in the intention-to-treat populations (ITT). Efficacy against CIN1+ was similar in scale in favor of vaccine. Overall vaccines were highly efficacious against 6-month persistent infection with HPV 16 and 18, both in the PPP cohort (RR: 0.06 [0.04-0.09] and 0.05 [0.03-0.09], respectively), and the ITT cohorts (RR: 0.15 [0.10-0.23] and 0.24 [0.14-0.42], respectively). There was limited prophylactic effect against CIN2+ and 6-month persistent infections associated with non-vaccine oncogenic HPV types. The risk of serious adverse events (RR: 1.00, 0.91-1.09) or vaccine-related serious adverse events (RR: 1.82; 0.79-4.20) did not differ significantly between vaccine and control groups. Data on abnormal pregnancy outcomes were underreported.ConclusionsProphylactic HPV vaccines are safe, well tolerated, and highly efficacious in preventing persistent infections and cervical diseases associated with vaccine-HPV types among young females. However, long-term efficacy and safety needs to be addressed in future trials.

HPV prophylactic vaccination: The first years and what to expect from now

New prophylactic HPV vaccines have the power to prevent many HPV infections, thus reducing the burden of HPV-associated diseases. Two vaccines composed of HPV L1 proteins self assembled into virus-like particles (VLPs) have been developed: one containing VLPS of HPV types 6, 11, 16 and 18, while the other vaccine is composed of HPV 16 and 18 VLPs. Large phase II and III clinical trials to assess prophylactic efficacy have been conducted in which both HPV infection endpoints and disease endpoints were evaluated, particularly high-grade cervical intraepithelial neoplasia – CIN2 or CIN3 – as well as vulvar and vaginal intraepithelial neoplasias – VIN or VaIN – and genital warts for the quadrivalent vaccine. Very high efficacy rates were observed in different populations that included young women between 16 and 26years of age, and older (up to 55). More recently, the quadrivalent vaccine has been shown to be efficacious in men to prevent genital and anal infection and disease caused by the types included in the vaccine. Based on demonstrated clinical efficacy and favorable safety profile, HPV prophylactic vaccine are being introduced worldwide aiming the reduction of the morbidity and mortality of tumors caused by HPV. From 2006 when first approved in the USA, hundreds of countries have licensed the HPV vaccines, a significant proportion of which are offering the vaccine to young women in national immunization programs supported by the government. The ultimate goal is to implement worldwide cervical cancer control programs to include HPV vaccination and screening with cytology and HPV DNA testing, particularly in less-developed countries where it is most needed.

A Global Review of Age-Specific and Overall Prevalence of Cervical Lesions

Overall and age-specific cervical cytological and histological abnormalities prevalence data across geographical regions, in conjunction with human papillomavirus vaccination status, will be important for the future evaluation of HPV prophylactic vaccine effectiveness. A systematic review was conducted to summarize worldwide data on the prevalence of high- and low-grade squamous intraepithelial lesions, and cervical intraepithelial neoplasia (CIN) 2/3 or 1. More than 12,400,000 women were included in 103 studies. Most studies were from Europe and Middle East (40%) or North America (14%), 14% were from Asia, 17% from Central and South America, and 15% from Africa. Age-specific data were limited from Asia, Central and South America, and Africa. Screening techniques and study exclusion criteria varied, depending on region and population surveyed. Age trends of high-grade cervical lesions seemed to peak at a relatively younger age in North America (<30 years), compared with 25 to 40 years in Europe and Middle East, Africa, Asia, and Central and South America. Age patterns of low-grade lesions generally declined after a peak in the younger age groups (20-30 years). Age-specific CIN 1 and CIN 2/3 prevalence were lower compared with low- and high-grade squamous intraepithelial lesions from the same studies, respectively. Variation in the age patterns of high-grade lesions across regions is likely attributable to differences in age at screening initiation, frequency, coverage, and rates of follow-up of women with cervical abnormalities. Observed age patterns of low-grade lesions are generally consistent to those of human papillomavirus infection in women worldwide. Potential factors contributing to variations in the burden of cytological and histological abnormalities across studies include subjectivity in evaluating cytological slides and discrepancies in the processing, referral rates, and diagnostic interpretation of colposcopically directed biopsy.