Human Papilloma Virus (HPV) and Host Cellular Interactions

Viral-induced carcinogenesis has been attributed to the ability of viral oncoproteins to target and interact with the host cellular proteins. It is generally accepted that Human papilloma virus (HPV) E6 and E7 function as the dominant oncoproteins of ‘high-risk’ HPVs by altering the function of critical cellular proteins. Initially it was shown that HPV E6 enhances the degradation of p53, while HPV E7 inactivates the function of the retinoblastoma tumor suppressor protein Rb. However, recent studies during the last decade have identified a number of additional host cellular targets of both HPV E6 and E7 that may also play an important role in malignant cellular transformation. In this review we present the interactions of HPV E6 and E7 with the host cellular target proteins. We also present the role of DNA integration in the malignant transformation of the epithelial cell.     

Human Papilloma Virus Vaccination in Nepal: An InitialExperience

Cervical cancer is the commonest cancer among women in Nepal. Human papilloma virus (HPV) infection,a recognized cause of cervical cancer, is very common in sexually active women and HPV vaccination has beenrecommended as a prophylactic therapy. If HPV infection is prevented by the HPV vaccination to the adolescentgirls, cervical cancer is also prevented. We received 3,300 vials of quadrivalent human papilloma virus (types 6,11, 16, 18) recombinant vaccine (Gardasil; Merk & Co.) as a gift from the Australian Cervical Cancer Foundation(ACCF) which has a mission to provide life-saving HPV cervical cancer vaccines for women in developingcountries, who cannot otherwise afford vaccination. HPV vaccine was offered to 1,096 of 10 to 26 year aged girlsattending 17 secondary schools. In total, 1,091 (99.5%) received the second dose and 1,089 (99.3%) received thethird dose of the vaccine. The remaining 5 girls at second dose and 2 girls at third dose remained unvaccinated.No serious vaccine related adverse events were reported except mild pain at the injection site in 7.8% of thevaccine recipients. High cost and low public awareness are the key barriers for successful implementation ofthe vaccination program in resource limited developing countries. In conclusion, HPV vaccine is safe with highacceptability in Nepalese school girls. However a large population study for longer follow up is warranted tovalidate the findings of this vaccination program.     

Knowledge,Acceptance, and Willingness to Pay for Human Papilloma Virus (HPV) Vaccination among Female Parents in Thailand

Background: This study aimed to examine the level of knowledge, attitude, acceptance, and willingness to pay (WTP) for HPV vaccination among female parents of girls aged 12-15 years in Thailand. Materials and Methods: A cross-sectional survey was conducted in eight schools across Bangkok. Results: Of 1,200 questionnaires sent out, a total of 861 questionnaires were received. Knowledge regarding the HPV vaccine among parents was quite low. Only half of the parents knew about the link between HPV and cervical cancer while one-third of them knew that the vaccine should be administered to the children before they become sexually active. Nevertheless, vaccine acceptance was high if it was offered for free: 76.9% for the bivalent and 74.4% for the quadrivalent vaccine. The proportion of respondents who were willing to copay for the vaccine if it was not totally free was also high, ranging from 68.9% for the bivalent to 67.3% for the quadrivalent vaccine. No significant difference between bivalent and quadrivalent vaccines in terms of prevalence of acceptance and willingness to pay was found. About one-third of the participants, who were willing to copay for the vaccine if it was not offered for free, indicated that they would copay less than 500 baht (30 baht = approx US$1) for three doses of bivalent vaccine. Conclusions: Substantial effort should be made to educate parents prior to introduction of a national HPV vaccination program. In terms of acceptance, either bivalent or quadrivalent vaccines can be recommended.     

宫颈癌组织HPV16DNA相关序列检测与临床分析

用Southern blot核酸杂交技术检测宫颈组织HPV 16 DNA相关序列。山东省儿6例宫颈癌病人的癌组织HPV 16 DNA相关序列阳性率为50.9％,36例无宫颈疾病妇女的宫颈组织阳性率为5.6％,宫颈癌与HPV 16感染有很强的联系,OR=17.60,x~2=23.47,P<0.001.HPV 16 DNA相关序列阳性率与宫颈癌病人的年龄、肿瘤的组织类型、临床类型及临床分期均无统计学联系(P均大于0.25).本文首次从山东省宫颈癌病人癌组织中检测到HPV 33 DNA4例及HPV31 DNA 1例。     

人乳头瘤病毒检测对宫颈病变的诊断价值

目的：比较分析阴道镜活检与人乳头瘤病毒（ HPV）检测对宫颈病变诊断的临床应用价值。方法选取接受宫颈病变筛查的2560例已婚妇女为研究对象,其中行阴道镜活检560例,行HPV检测2000例,对两组检查结果进行对比分析。结果560例妇女阴道镜活检HPV阳性率为44．46％,2000例妇女HPV检测HPV阳性率为42．55％,两组比较差异无统计学意义,P＞0．05。经后期确认,上述患者中宫颈囊肿患者180例,阴道镜活检检出172例,漏诊8例,漏诊率为4．44％;HPV检测检出102例,漏诊78例,漏诊率为43．33％,阴道镜活检的漏诊率明显低于HPV检测,P＜0．01,差异具有统计学意义。结论阴道镜活检与HPV检测在宫颈病变诊断中均有良好效果,根据具体情况选择合适的检测方式。     

Community-Based Prevalence of Genital Human Papilloma Virus (HPV) Infection: a Systematic Review and Meta-Analysis

Introduction: Cervical cancer probably represents the best-studied human cancer caused by a viral infection and the causal association of this preventable cancer with human papilloma virus (HPV) is well established. Worldwide there is a scarcity of data regarding HPV prevalence with vast differences existing among populations. Objective: The aim of this meta-analysis was to determine the community-based HPV prevalence estimates among asymptomatic women from urban and rural set ups and in participants of cancer screening clinics. Study design: Systematic review and meta-analysis. Methods: PubMed-Medline, CINAHL, Scopus, and Google scholar were systematically searched for studies providing prevalence data for HPV infection among asymptomatic women between 1986 and 2016. Results: The final analysis included 32 studies comprising a population of 224,320 asymptomatic women. The overall pooled HPV prevalence was 11% (95% confidence interval (CI), 9%-12%). The pooled HPV prevalence of 11% (95% CI, 9%-11%) was observed among women attending cervical cancer screening clinics. The pooled HPV prevalences were 10% (95% CI 8%-12%) and 11% (95% CI 4%-18%) from urban and rural areas respectively, indicating higher infection rates among the rural women with the least access to cancer screening and cancer care. Conclusion: The prevalence rates in this systematic quantitative review provide a reliable estimate of the burden of HPV infection among asymptomatic women from developed as well as developing nations. Rural women and women attending cervical cancer screening programmes feature higher genital HPV prevalences compared to their urban counterparts.     

Knowledge,Attitudes and Barriers for Human Papilloma Virus (HPV) Vaccines among Malaysian Women

A cross-sectional study was conducted among 300 Malaysian women in the obstetrics and gynecology outpatient clinic in a selected hospital in Bangi, Selangor to determine the level of knowledge of HPV and HPV vaccines, attitudes toward HPV vaccination and barriers of being vaccinated. Factors associated with knowledge and attitudes were also addressed with a questionnaire. Seventy eight women (26%) had heard about the HPV virus and 65 about HPV vaccines (21.7%). Marital status was associated significantly with awareness of HPV and HPV vaccine (p=0.002, p=0.002; respectively), in addition to level of education (p=0.042). The percentages of women who reported correct answers for the questions on knowledge of HPV and HPV vaccine ranged from 12% to 25%. One hundred fifty nine respondents (53%) had a positive attitude toward HPV vaccination. Age, marital status, and level of education were associated significantly with attitude (p<0.001, p<0.001, p=0.002; respectively). The most important barriers reported were ‘unawareness of the vaccine’ ‘concerned about side effects’ and ‘afraid of needles’. This study found a very low level of knowledge of HPV and HPV vaccine. Education of population is highly recommended and barriers to being vaccinated should be dealt with seriously.     

Acceptability of Human Papilloma Virus Vaccination among Women in the United Arab Emirates

Background: Human papilloma virus (HPV) is a common sexually transmitted infectious agent. It is estimatedthat 10% of all women worldwide are infected with HPV, that is some 660 million each year. HPV vaccination hasa reported efficacy of more than 98% for protection against infection in females. In 2008 the Abu Dhabi HealthAuthority in the United Arab Emirates (UAE) introduced free HPV vaccination for all eligible schoolgirls in bothpublic and private schools. Methods: A cross-sectional study of 640 women aged 18-50 years in the Emirate ofAbu Dhabi in UAE from April 2012 to October 2012 was conducted. Results: Thirty-seven percent of the womenin our sample had heard about HPV vaccination, and 80% of these would consider getting vaccinated themselves,and 87% would recommend vaccination to relatives or friends. Most women in the study (69%) had a favorableopinion about the vaccine. Only 17% of the women felt it might not be culturally acceptable, and 1% felt thatthere might be religious objections to HPV vaccination. Vaccine safety and recommendation by a doctor (36%each) were the factors identified most frequently by our sample of women which would enhance the uptake ofthe HPV vaccination. Conclusions: Knowledge about HPV vaccination among women in our sample was belowaverage (37%); however, 80% of those who had heard about HPV vaccination were willing to be vaccinatedthemselves, and 87% would recommend vaccination to relatives and friends.     

Human Papillomavirus (HPV) Health Savings as an Alternative Solution: HPV Vaccination Behavior in Adolescents

Objective: This study aimed to measure the effects of reproductive health savings (tabungan kesehatan reproduksi, Takespro) on human papillomavirus (HPV) vaccine initiation program and the quality of the decision making to get vaccinated, as measured by knowledge, attitudes, beliefs, and self-efficacy toward HPV vaccination. Methods: This quasi-experimental study was conducted on 128 students randomly allocated to intervention and control groups. This research was conducted in junior high schools. The intervention group received the health education “Takespro HPV” intervention through videos and booklets for 6 months at school. Participants in the control group received usual care from the school. Data were collected using a questionnaire of knowledge, attitudes, beliefs, and self-efficacy about HPV vaccination modified by researchers based on previous research and tested for validity and reliability. Data were analyzed using Mann–Whitney test and independent t-test. Results: A total of 40 participants were actively enrolled in the intervention group, and 88 were passively enrolled in the control group. The health education that was part of the Takespro HPV intervention improved the knowledge (p < 0.05) and self-efficacy (p < 0.05) of the intervention group compared with the control group. The attitude and belief variables showed no significant difference (p > 0.05). Forty students exhibited the health reproduction savings behavior at schools. However, the savings amount was insufficient to get HPV vaccination at the initiation phase. Conclusion: “Takespro” HPV intervention can be considered an alternative to increasing the coverage of HPV vaccination in adolescents in Yogyakarta.     

Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma.     

Characterization of the Human Papillomavirus (HPV) Integration Sites into Genital Cancers

Oncogenic HPVs have been found frequently integrated into human genome of invasive cancers and chromosomal localization has been extensively investigated in cervical carcinoma. Few studies have analyzed the HPV integration loci in other genital cancers. We have characterized the integration sites of HPV16 in invasive penile carcinoma by means of Alu-HPV-based PCR. Nucleotide sequence analysis of viral-human DNA junctions showed that HPV integration occurred in one case within the chromosome 8q21.3 region, in which the FAM92A1 gene is mapped, and in the second case inside the chromosome 16p13.3, within the intronic region of TRAP1 gene. These results confirm previous observations, summarized in a systematic review of the literature, on the HPV integration events in gene loci relevant to cancer pathogenesis.     

Detection of Human Papilloma Virus (HPV) in oral mucosa of women with cervical lesions and their relation to oral sex practices

Background  

Previous studies have either investigated the relationship of HPV with oral cancer or the prevalence of HPV on the oral cavity. The purpose of this investigation was to study the prevalence of HPV in oral cavity of women with oral sex practices and cervical lesions.     

Prospective Study of Antibody to Human Papilloma Virus type 16 and Risk of Cervical, Endometrial, and Ovarian Cancers (United States)

Objective: Human papilloma virus (HPV) is frequently detectable in cancers of the cervix, vagina, and vulva, but its role in endometrial and ovarian cancers is less certain. This analysis aimed to examine the association of presence of HPV type 16 (HPV-16) antibodies with subsequent risk of cervical, endometrial, and ovarian cancers. Methods: In a prospective study enrolling over 15,000 pregnant women, pre-cancer sera from women who developed cervical (n = 83), endometrial (n = 34), and ovarian (n = 35) cancers were compared with sera from 172 control women frequency-matched by age group and race. Results: HPV-16 seropositivity (OR = 2.0, 95% CI 1.0–3.4) was associated with cervical cancer, with the association more prominent for cancers occurring within 10 years of serum sampling (OR = 2.3, 95% CI 1.0–5.3) than cancers occurring later (OR = 1.6, 95% CI 0.75–3.6). Overall, the associations between HPV-16 seropositivity and endometrial (OR = 1.6, 95% CI 0.64–3.8) and ovarian cancers (OR = 1.1, 95% CI 0.43–2.8) were not significant, although the odds ratios for those cancers occurring within 20 years after serum sampling were similar to that for cervical cancer (OR = 2.2 for both). Conclusions: Our results confirm that HPV-16 infection precedes the development of cervical cancer. Predictability of HPV-16 seropositivity for risk of other female cancers warrants further investigation.     

Vaccination against HPV: boosting coverage and tackling misinformation

The availability of human papillomavirus (HPV) vaccines and screening tests has raised the possibility of globally eliminating cervical cancer, which is caused by HPV. Cervical cancer is a very common malignancy worldwide, especially among deprived women. High vaccination coverage is key to the containment and eventual elimination of the infection. Public HPV vaccination programmes in Italy and Denmark were swiftly established and are among the most successful worldwide. Still, in both countries, it has been challenging to achieve and maintain the recommended coverage of > 80% in girls. In a well‐studied Italian region, vaccination coverage in girls at age 15 years (World Health Organization''s gold standard) reached 76% in 2015 but decreased to 69% in 2018, likely due to work overload in public immunization centres. In Denmark, doubts about safety and efficacy of the HPV vaccine generated a decline in coverage among girls age 12–17, from 80% in 2013 down to 37% in 2015, when remedial actions made it rise again. Insights from these two countries are shared to illustrate the importance of monitoring coverage in a digital vaccine registry and promptly reacting to misinformation about vaccination.

Abbreviations

CC

cervical cancer

FVG

Friuli Venezia Giulia

HICs

high‐income countries

HPV

human papillomavirus

LMICs

middle‐income countries

WHO

World Health Organization

     

Determinants of Human Papillomavirus (HPV) Vaccination Intent Among Three Canadian Target Groups

To increase the uptake of the human papillomavirus (HPV) vaccine, understanding the determinants of vaccination intentions for various groups is important. Three studies examining theoretical determinants of college-aged women’s (study 1: n?=?286), parents’ of daughters (study 2: n?=?230) and parents’ of sons (study 3: n?=?137) HPV vaccination intentions were conducted. Participants completed questionnaires assessing constructs of protection motivation theory (PMT) and the theory of planned behaviour (TPB). Results indicate that both PMT and TPB constructs predict intentions for the different groups. Focusing on the response efficacy of the vaccine rather than the severity of contracting HPV may be an effective way to increase vaccination intentions among all groups. Focusing on vulnerability to HPV may only increase intentions among college-aged women and parents of sons, and increasing self-efficacy may only increase intentions among college-aged women and parents of daughters. Findings have implications for understanding differences among groups considering HPV vaccination and tailoring interventions.     

Simultaneous Effects of Viral Factors of Human Papilloma Virus and Epstein-Barr Virus on Progression of Breast and Thyroid Cancers: Application of Structural Equation Modeling

This study aimed to assess effects of the sets of EBV and HPV expressed proteins simultaneously on the sets of cellular/inflammatory factors in breast and thyroid cancers using structural equation modeling. In this multi-center case-control study, according to the inclusion and exclusion criteria, 83 breast and 57 thyroid specimens were collected from the eligible patients. In addition, 31 and 18 histopathological evaluated normal breast and thyroid samples were also examined as age-matched healthy controls. In addition, ELISA and Real-time PCR were used to measure the expression level of viral and cellular/inflammatory genes and proteins. Structural equation modeling was used to test the causal associations between the sets of EBV and HPV expressed proteins with inflammatory factors in breast and thyroid cancers development. Breast cancer patients had a higher incidence of HPV-positively and EBV-positively than healthy controls (OR=1.66, 95%CI=0.79-3.47, P-value=0.177), (OR=3.18, 95%CI=1.52-6.63, P-value=0.002), respectively. In addition, thyroid cancer patients had a significantly higher incidence of EBV-positivity than healthy controls (OR=3.72, 95% CI=1.65-8.36, P-value=0.001). After fitting the SEM model, HPV proteins factor has significant direct and total effects on the cellular/inflammatory factors in breast cancer (direct effect: β=0.426, P-value=0.01; total effect: β=0.549, P-value<0.001). However, EBV proteins factor has most significant total effect on the cellular/inflammatory factors in breast cancer (total effect: β=0.804, P-value<0.001) than the cellular/inflammatory factors in thyroid cancer (total effect: β=0.789, P-value<0.001). For the first time, a significant association between EBV and HPV -genes, anoikis resistance and the development of breast and thyroid cancers demonstrated by using SEM, Simultaneously.     

Epidemiological Features of Human Papillomavirus (HPV) Infection among Women Living in Mainland China

Cancer of the cervix is the third most common cancer in women worldwide, more than 85% of the casesoccurring in developing countries such as China. In China, since a national cancer registry is already set up butwith geographically limited data generated, the burden of cervical cancer is believed to be underestimated. Highriskhuman papillomavirus (HR-HPV) prevalence among women attending routine cervical cancer screeningprograms has been shown to correlate well with cervical cancer incidence rates based on independently obtainedHPV prevalence data as well as findings for the worldwide cervical cancer burden. Therefore, reviewing dataon HR-HPV prevalence in population-based screening studies and hospital-based case studies will be importantin the context of better understanding the cervical cancer burden and for the evaluation of the potential impactof HPV vaccination in the country. With the advent of prophylactic vaccines, significant progress is likely tobe made in cervical cancer prevention. This article reviews available data on the HPV epidemiology over a12-year time period (2001-2012) in mainland China under different epidemiological aspects: by age group ofstudy population, by ethnicity, by geographic area, as well as time period. The authors also review the potentialacceptability of HPV vaccination among Chinese women.     

人乳头瘤病毒疫苗的临床研究进展

人乳头瘤病毒（HPV）是宫颈癌的主要病因,HPV疫苗在预防宫颈癌的发生方面备受关注。目前研制成功的有HPV16、18二价疫苗和HPV6、11、16、18四价疫苗,随着时间的推移,越来越多的热点问题被进一步分析研究。文章就HPV疫苗预防宫颈癌的临床最新研究动态作一综述。     

Predictive Value of Anti- E6 Oncoprotein (High Risk- Human Papilloma Virus) and p16 Ink4a for Detecting HPV in Oral Epithelial Dysplasia

Aim: The aim of this study was to evaluate the expression of human papillomavirus (HPV) in oral potentially malignant disorders (OPMD) and to examine the association of HPV in histological grades of dysplasia using p16 and Anti-E6 oncoprotein immunohistochemistry (IHC). Subjects and methods: This study focused on clinically diagnosed oral potentially malignant disorders. Clinical parameters such as age, gender, habits, occupation, duration, site, and the type of the lesions were examined and the incisional biopsy was done on the selected cases for the histopathological diagnosis. Selected cases of OPMDs were screened immunohistochemically for HPV 16 and HPV 18 (high-risk group) positivity using p16INK4a and Anti-E6 oncoprotein. The immunohistochemical p16 expression was evaluated based on (a) percentage of p16 positive cases and (b) pattern of p16 staining in various grades of OPMD. Results: Anti-E6 oncoprotein (HR-HPV) expression level was only detected in 11 cases (37%), and positive expression of p16 was found in three cases (10%), with variation in cell proportion and intensity. Subsequently, the association between p16 expression level and clinicopathological characteristic factors was analyzed and a significant association was found between age and histopathology. Conclusion: There was an association between HPV and OPMD. Both biomarker tests, HPV E6 and p16 immunocytochemistry had a specific role in the detection of HR-HPV. Anti-E6 immunocytochemistry can be a valuable test with higher specificity for HPV DNA detection in oral epithelial dysplasia without losing sensitivity.