HPV,Cervical Cancer and Pap Test Related Knowledge Among a Sample of Female Dental Students in India

Background: The present study was designed to ascertain knowledge about HPV, cervical cancer (CC) andthe Pap test among female dental students of Panineeya Institute of Dental Sciences and Hospital, Hyderabad,India. Materials and Methods: A self-administered questionnaire covering demographic details, knowledgerelating to human papilloma virus (HPV) (8 items), cervical cancer (4 items) and the Pap smear (6 items) wasemployed. Responses were coded as “True, False and Don’t Know”. Mean and standard deviation (SD) for correctanswers and levels of knowledge were determined. Results: Based on the year of study, significant differences inknowledge of HPV werenoted for questions on symptoms (p=0.01); transmission from asymptomatic partners(p=0.002); treatment with antibiotics (p=0.002); start of sexual activity (p=0.004); and recommended age for HPVvaccination (p=0.01). For knowledge regarding CC, significance was observed for the age group being affected(p=0.008) and symptoms of the disease in early stages (p=0.001). Indications for Pap smear tests like symptoms’ ofvaginal discharge (p=0.002), marital status (p=0.01) and women with children (p=0.02) had significant differencebased on the year of study. Based on religion, transmission of HPV via pregnancy, HPV related diseases exceptCC and preventive measures except condom use and oral contraceptives showed significant differences. However,significant variation with religion was observed only for two preventive measures of CC (Pap test; p=0.004) andHPV vaccination (p=0.003). Likewise, only the frequency of Pap test showed a significant difference for religion(p=0.001). Conclusions: This study emphasizes the lack of awareness with regard to HPV, CC and screeningwith pap smear even among health professionals. Hence, regular health campaigns are essential to reduce thedisease burden     

Development and Clinical Evaluation of Dendritic Cell Vaccines or HPV Related Cervical Cancer - a Feasibility Study

Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in thedevelopment of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC),they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintainand characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomizedPhase I trial with three arms - saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysateprimed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or gradeone toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells andlater cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remaineddisease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sforcervical cancer treatment and further studies to improve their efficacy need to be conducted.     

Population-based Cervical Cancer Screening Using Highrisk HPV DNA Test and Liquid-based Cytology in Northern Thailand

Background: Northern Thailand is a region with a high cervical cancer incidence. Combined high-risk HPV (hrHPV) DNA testing and cytology (co-testing) has increasingly gained acceptance for cervical cancer screening. However, to our knowledge, data from a population-based screening using co-testing have not been available in this region. This study therefore aimed to evaluate the performance of cytology and hrHPV test in women in northern Thailand. Materials and Methods: Cervical samples were collected for hybrid capture 2 (HC2) testingand liquid-based cytology from women aged 30 to 60 years who were residents in 3 prefectures of Chiang Mai in northern Thailand between May and September 2011. Women with positive cytology were referred to colposcopy, while women with positive for HC2 only were followed for 2 years. Results: Of 2,752 women included in this study, 3.0% were positive in both tests, 4.1% for HC2 only, and 1.3% had positive cytology only. At baseline screening, positive HC2 was observed in 70.6% among cytology-positive women compared with 4.3% amongcytology-negative women. The prevalence of positive HC2 or cytology peaked in the age group 35-39 years and was lowest in the age group 55-60 years. High-grade squamous intraepithelial lesion or worse lesions (HSIL+) were histologically detected in 23.5% of women with positive baseline cytology and in 9.8% of women with positive baseline HC2 only on follow-up. All women with histologic HSIL+ had positive baseline HC2. Conclusions: The hrHPV test is superior to cytology in the early detection of high-grade cervical epithelial lesions. In this study, the prevalence of histologic HSIL+ on follow-up of women with positive hrHPV test was rather high, and these women should be kept under careful surveillance. In northern Thailand, hrHPV testing has a potential to beused as a primary screening test for cervical cancer with cytology applied as a triage test.     

Validation of a DNA methylation HPV triage classifier in a screening sample

High‐risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV‐positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV‐positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV‐positive women on original screening specimens might be a valid approach with better performance than genotyping.     

宫颈刮片、阴道镜及HPV检测在宫颈癌筛查中的应用

目的 评价宫颈刮片、阴道镜及高危HPV检测在宫颈癌筛查中的作用.方法 对发现宫颈异常的患者同时进行宫颈刮片、阴道镜检查及高危HPV检测,对一项或多项异常者行病理组织学检查,并以病理结果为金标准.对167例病检结果阳性(CIN Ⅰ、CIN Ⅱ、CIN Ⅲ、宫颈浸润癌)的患者,比较三种方法的检出敏感性、特异性、阳性预测值和阴性预测值.结果 宫颈刮片检测的敏感性为37.72%,特异性为89.01%,阳性预测值为54.07%,阴性预测值为83.74%;阴道镜检敏感性为61.08%,特异性为70.51%,阳性预测值为33.75%,阴性预测值为81.91%;高危HPV感染阳性126例,敏感性75.45%,特异性为57.51%,阳性预测值为35.2%,阴性预测值为88.45%.三种方法的敏感性比较差异有统计学意义(P＜0.05).结论 对于宫颈癌及其癌前病变的筛查及早期诊断,应以宫颈细胞学检查和阴道镜检查及高危HPV检测相互结合以提高检出率,降低假阴性.     

Cervical Cancer and HPV Vaccines in Developing Countries

Cervical cancer is the second most common cancer among women in the world. Despite a decline of up to70% in its incidence and prevalence through screening programs, it is still the most common gynecologicalcancer worldwide. Since the human papilloma virus (HPV) was conclusively identified as the etiological factorinducing cervical cancer, investigations during the last two decades have been concentrating on producing avaccine against HPV virus. Thus prevention of HPV infection has been the main purpose and vaccination isexpected to reduce up to 70% of related cervical cancer and prevent precancerous and cancerous lesions of thegenitalia. However, screening programs are still essential for those who have already been exposed to the highrisk forms of the virus and educational and information programs continue to play important roles to increasethe success rate of screening, by whichever of the modalities is most appropriate for the local conditions.     

Performance of HPV DNA Testing with Hybrid Capture 2 in Triaging Women with Minor Cervical Cytologic Abnormalities (ASC-US/LSIL) in Northern Thailand

Background: Minor cervical cytologic abnormalities include atypical squamous cells of undeterminedsignificance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Approximately 10-20% of womenwith minor cytologic abnormalities have histologic high-grade squamous intraepithelial or worse lesions (HSIL+).In Thailand, women with minor cytologic abnormalities have a relatively high risk of cervical cancer, and referralfor colposcopy has been suggested. A triage test is useful in the selection of women at risk for histologic HSIL+ toreduce the colposcopy burden. The aim of this study was to assess the performance of high-risk HPV DNA test intriage of women with minor cytologic abnormalities in northern Thailand. Materials and Methods: All womenwith ASC-US/LSIL cytology who were referred to our colposcopy clinic from October 2010 to February 2014were included. HPV DNA testing was performed using Hybrid Capture 2 (HC2). All patients received colposcopicexamination. Accuracy values of HC2 in predicting the presence of histologic HSIL+ were calculated. Results:There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity rate was significantlyhigher in the LSIL group than in ASC-US group (74.8% versus 41.0%, p<0.001). Histologic HSIL+ was detectedin 9 women (7.4%) in the ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was nohistologic HSIL+ detected among HC2-negative cases (sensitivity and negative predictive value of 100%). Theperformance of HC2 triage was highest among women aged >50 years with ASC-US cytology. An increase in thecut-off threshold for positive HC2 resulted in a substantial decrease of sensitivity and negative predictive value.Conclusions: HPV DNA testing with HC2 shows very high sensitivity and negative predictive value in triage ofwomen with minor cervical cytologic abnormalities in northern Thailand. An increase of the cut-off thresholdfor HC2 triage is not recommended in this region.     

Distribution of HPV Genotypes in Cervical Cancer in Multiethnic Malaysia

Background: Cervical cancer is the third commonest type of cancer among women in Malaysia. Our aim wasto determine the distribution of human papilloma virus (HPV) genotypes in cervical cancer in our multi-ethnicpopulation. Materials and Methods: This was a multicentre study with a total of 280 cases of cervical cancer from4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 highrisk-HPV genotypes. Results: Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomasand 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%),58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPVinfections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9%and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that thepercentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) andIndians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%)and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detectedin the Chinese (p<0.05). Conclusions: This study showed that the distribution of HPV genotype in Malaysia issimilar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have differentHPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.     

Cervical Cancer Prevention Through HPV Vaccination in Low- and Middle-Income Countries in Asia

Cervical cancer is ranked the first or second most common cancer in women of low- and middle-income countries (LMICs) in Asia. Cervical cancer is almost exclusively caused by human papillomavirus (HPV), and majority of the cases can be prevented with the use of HPV vaccines. The HPV vaccines have demonstrated high vaccine efficacies against HPV infection and cervical cancer precursors in clinical and post-marketing studies, and are in use in most high-income countries. However, their use in LMICs are limited mainly due to the high costs and logistics in delivering multiple doses of the vaccine. Other issues such as the safety of the vaccines, social and cultural factors, as well as poor knowledge and awareness of the virus have also contributed to the low uptake of the vaccine. This mini-review focuses on the need for HPV vaccine implementation in Asia given the substantial disease burden and underuse of HPV vaccines in LMICs in this region. In addition, the progress towards HPV vaccine introduction, and barriers preventing further rollout of these essential, life-saving vaccines are also discussed in this article.     

Identification of HPV Integration and Genomic Patterns Delineating the Clinical Landscape of Cervical Cancer

Cervical cancer is one of the most common cancers in women worldwide. During their life time the vast majority of women become infected with human papillomavirus (HPV), but interestingly only a small portion develop cervical cancer and in the remainder infection regresses to a normal healthy state. Beyond HPV status, associated molecular characterization of disease has to be established. However, initial work suggests the existence of several different molecular classes, based on the biological features of differentially expressed genes in each subtype. This suggests that additional risk factors play an important role in the outcome of infection. Host genomic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review was to compile advances in the field of host genomics of HPV positive and negative cervical cancer and their association with clinical response.     

深圳市原住居民女性生殖道HPV感染

[目的]了解深圳市原住居民女性人群的生殖道高危型人乳头瘤病毒（HPV）感染现状、宫颈上皮内瘤样病变（CIN）和宫颈癌的现患率。[方法]2009年6月至2009年10月在深圳市龙岗区坑梓街道办事处辖区25~59岁、3年内未做过宫颈癌筛查的原住居民女性进行整群抽样,并以同一辖区外来移民女性为对照。所有接受筛查女性均行宫颈液基细胞学检查及第二代杂交捕获技术（hybrid captureⅡ,HC-Ⅱ）高危型HPV检测。HPV阳性和/或细胞学≥ASCUS的女性行阴道镜检查和活检。[结果]共有942名原住居民妇女和1183名外来移民女性参加了本次调查。原住居民与外来移民妇女HPV阳性率分别为16.9%和11.8%（P〈0.05）。原住居民妇女CIN现患率为9.7%,其中CINⅡ及以上病变现患率为6.3%,外来移民CIN现患率5.1%,其中CINⅡ及以上病变现患率为2.6%。原住居民妇女CIN和CINⅡ及以上病变现患率均明显高于外来移民（P〈0.001）,尤以30~39岁年龄组最为明显。[结论]30~39岁年龄组妇女HPV感染和CIN现患率均较高,应作为宫颈癌防治的重点监测对象。     

Knowledge and Awareness of Human Papillomavirus (HPV), Cervical Cancer and HPV Vaccine among Women in Two Distinct Nepali Communities

Background: This study assessed human papillomavirus (HPV), cervical cancer, and HPV vaccine knowledgeand awareness among women in two sub-populations in Nepal - Khokana, a traditional Newari village in theLalitpur District about eight kilometers south of Kathmandu, and Sanphebagar, a village development committeewithin Achham District in rural Far-Western Nepal. Methods: Study participants were recruited during healthcamps conducted by Nepal Fertility Care Center, a Nepali non-governmental organization. Experienced staffadministered a Nepali language survey instrument that included questions on socio-demographics, reproductivehealth and knowledge on HPV, cervical cancer, and the HPV vaccine. Results: Of the 749 participants, 387 (51.7%)were from Khokana and 362 (48.3%) were from Sanphebagar. Overall, 53.3% (n=372) of women were awareof cervical cancer with a significant difference between Khokana and Sanphebagar (63.3% vs 43.0%; p=0.001).Overall, 15.4% (n=107) of women had heard of HPV and 32% (n=34) of these women reported having heard ofthe HPV vaccine. If freely available, 77.5% of the women reported willingness to have their children vaccinatedagainst HPV. Factors associated with cervical cancer awareness included knowledge of HPV (Khokana: OddsRatio (OR)=24.5; (95% Confidence Interval (CI): 3.1-190.2, Sanphebagar: OR=14.8; 95% CI: 3.7-58.4)) andsexually transmitted infections (Khokana: OR=6.18; 95% CI: 3.1-12.4; Sanphebagar: OR=17.0; 95% CI: 7.3-39.7) among other risk factors. Conclusions: Knowledge and awareness of HPV, cervical cancer, and the HPVvaccine remains low among women in Khokana and Sanphebagar. Acceptance of a freely available HPV vaccinefor children was high, indicating potentially high uptake rates in these communities.     

HPV16 L1 and L2 DNA methylation predicts high‐grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology

DNA methylation changes in human papillomavirus type 16 (HPV16) DNA are common and might be important for identifying women at increased risk of cervical cancer. Using recently published data from Costa Rica we developed a classification score to differentiate women with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) from those with no evident high‐grade lesions. Here, we aim to investigate the performance of the score using data from the UK. Exfoliated cervical cells at baseline and 6‐months follow‐up were analyzed in 84 women selected from a randomized clinical trial of women undergoing surveillance for low‐grade cytology. Selection of women for the methylation study was based on detectable HPV16 in the baseline sample. Purified DNA was bisulfite converted, amplified and pyrosequenced at selected CpG sites in the viral genome (URR, E6, L1 and L2), with blinding of laboratory personnel to the clinical data. The primary measure was a predefined score combining the mean methylation in L1 and any methylation in L2. At the second follow‐up visit, 73/84 (87%) women were HPV16 positive and of these 25 had a histopathological diagnosis of CIN2/3. The score was significantly associated with CIN2/3 (area under curve = 0.74, p = 0.002). For a cutoff with 92% sensitivity, colposcopy could have been avoided in 40% (95% CI 27–54%) of HPV16 positive women without CIN2/3; positive predictive value was 44% (32–58%) and negative predictive value was 90% (71–97%). We conclude that quantitative DNA methylation assays could help to improve triage among HPV16 positive women.     

HPV Vaccination for Cervical Cancer Prevention is not Cost-Effective in Japan

Background: Our study objectives were to evaluate the medical economics of cervical cancer prevention and thereby contribute to cancer care policy decisions in Japan. Methods: Model creation: we created presenceabsence models for prevention by designating human papillomavirus (HPV) vaccination for primary prevention of cervical cancer. Cost classification and cost estimates: we divided the costs of cancer care into seven categories (prevention, mass-screening, curative treatment, palliative care, indirect, non-medical, and psychosocial cost)and estimated costs for each model. Cost-benefit analyses: we performed cost-benefit analyses for Japan as a whole. Results: HPV vaccination was estimated to cost $291.5 million, cervical cancer screening $76.0 million and curative treatment $12.0 million. The loss due to death was $251.0 million and the net benefit was -$128.5 million (negative). Conclusion: Cervical cancer prevention was not found to be cost-effective in Japan. While few cost-benefit analyses have been reported in the field of cancer care, these would be essential for Japanesepolicy determination.     

Cost-Effectiveness of HPV Vaccination in the Prevention of Cervical Cancer in Malaysia

Introduction: Cervical cancers (CC) demonstrate the second highest incidence of female cancers in Malaysia.The costs of chronic management have a high impact on nation’s health cost and patient’s quality of life that canbe avoided by better screening and HPV vaccination. Methodology: Respondents were interviewed from sixpublic Gynecology-Oncology hospitals. Methods include experts’ panel discussions to estimate treatment costsby severity and direct interviews with respondents using costing and SF-36 quality of life (QOL) questionnaires.Three options were compared i.e. screening via Pap smear; quadrivalent HPV Vaccination and combined strategy(screening plus vaccination). Scenario based sensitivity analysis using screening population coverage (40-80%)and costs of vaccine (RM 300-400/dose) were calculated. Results: 502 cervical pre invasive and invasive cervicalcancer (ICC) patients participated in the study. Mean age was 53.3 ± 11.21 years, educated till secondary level(39.39%), Malays (44.19%) and married for 27.73 ± 12.12 years. Life expectancy gained from vaccination is13.04 years and average Quality Adjusted Life Years saved (QALYs) is 24.4 in vaccinated vs 6.29 in unvaccinated.Cost/QALYs for Pap smear at base case is RM 1,214.96/QALYs and RM 1,100.01 at increased screening coverage;for HPV Vaccination base case is at RM 35,346.79 and RM 46,530.08 when vaccination price is higher. Incombined strategy, base case is RM 11,289.58; RM 7,712.74 at best case and RM 14,590.37 at worst case scenario.Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher is highly costeffective at RM 946.74 per QALYs saved and this is followed by combined strategy at RM 35,346.67 per QALYssaved. Conclusion: Vaccination increase life expectancy with better QOL of women when cancer can be avoided.Cost effective strategies will include increasing the Pap smear coverage to 70% or higher. Since feasibility andlong term screening adherence is doubtful among Malaysian women, vaccination of young women is a more costeffective strategy against cervical cancers.     

Knowledge and Attitudes of Medical and Non-Medical Turkish University Students about Cervical Cancer and HPV Vaccination

Background: This study was conducted to determine knowledge, attitudes and practices about cervical cancer and HPV vaccination of students studying in various faculties of Erciyes University. Materials and Methods: The study was performed among the first and fourth grade students of Medicine, Theology, Education and Economics and Administrative Sciences (FEAS) faculties of Erciyes University. It was aimed to reach 1,073 students and 718 were evaluated. A questionnaire consisting of 48 questions related to the socio-demographic characteristics, knowledge, attitude and practices about cervical cancer and HPV vaccination was administered to the students. The chi-square test and logistic regression were used for the statistical analyses. Results: Of the students, 78.3% were aware of cervical cancer, while 36.1% of them were aware of the HPV vaccine. The percentage hearing about cervical cancer and HPV vaccination was significantly higher among the students of the medical faculty than the others and among fourth grade students comparing with the first grade. The marital status and the presence of a health worker in the family had no significant impact on the knowledge level of the students. The acceptability of the HPV vaccination was low among all students. Conclusions: The knowledge levels of the university students about cervical cancer and HPV vaccination are inadequate. This deficiency is more pronounced among the non-medical students and there is no significant increase during the faculty years. Non-medical students must be provided with information about important public health issues by elective courses. HPV vaccination could provide many benefits for men and women by decreasing the morbidity and mortality of cervical, anal, and penile cancers.     

Clinical evaluation of human papillomavirus 16/18 oncoprotein test for cervical cancer screening and HPV positive women triage

The prognostic role of tumor‐infiltrating tryptase⁺ mast cells in human solid tumors remains controversial. Herein, we conducted a meta‐analysis including 28 published studies with 4224 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor‐infiltrating tryptase⁺ mast cells in human solid tumors. We found that tryptase⁺ mast cell infiltration significantly decreased overall survival (OS) and disease‐free survival (DFS) in all types of solid tumors. In stratified analyses, tryptase⁺ mast cell infiltration was significantly associated with worse OS in non‐small cell lung cancer, hepatocellular carcinoma and 5‐year survival in colorectal cancer. And these cells were inversely associated with DFS in hepatocellular and colorectal cancer. In addition, high density of intratumoral tryptase⁺ mast cells significantly correlated with lymph node metastasis of solid tumor. In conclusion, Tryptase⁺ mast cell infiltration leads to an unfavorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances and targeting it may have a potential for effective treatment.     

阴道乳酸杆菌与HPV感染、宫颈癌及癌前病变的相关性研究进展

乳酸杆菌及其代谢产物具有抑制肿瘤的作用,通过产生各种代谢产物干扰肿瘤代谢,以及激活机体免疫功能而发挥作用。乳酸杆菌在防治各种肿瘤中的作用也已引起重视。阴道乳酸杆菌是构成阴道微环境的重要因素,其数量的减少与HPV感染、宫颈癌前病变及宫颈癌有关。文章就阴道乳酸杆菌与HPV感染、宫颈癌及癌前病变的关系进行综述。