Human Papillomavirus (HPV), Vaccination, and Cervical Cancer
Human papillomavirus (HPV) is a common cause of infection. There are over 100 different sub-types of HPV. HPV types 16 and 18 cause 70% of cervical cancers and are also linked to cancers of the anus, vulva, vagina, penis, as well as the mouth and throat. Over time these can cause cells in the cervix to change, leading to precancerous conditions - cervical intraepithelial neoplasia (CIN), with a higher risk of developing cancer. Vaccination against HPV 16, 18 and other 'high risk' types of HPV reduces the risk of developing cervical and other HPV-related cancers.Information for Patients and the Public
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MeSH term: Uterine Cervical Neoplasms
US National Library of Medicine
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Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis.
Lancet. 2019; 394(10197):497-509 [PubMed] Related Publications
METHODS: In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.
FINDINGS: We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+. After 5-8 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0·17, 95% CI 0·11-0·25) among girls aged 13-19 years, and decreased significantly by 66% (RR 0·34, 95% CI 0·23-0·49) among women aged 20-24 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0·46, 95% CI 0·33-0·66) among girls aged 13-19 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0·33, 95% CI 0·24-0·46) among girls aged 15-19 years, decreased significantly by 54% (RR 0·46, 95% CI 0.36-0.60) among women aged 20-24 years, and decreased significantly by 31% (RR 0·69, 95% CI 0·53-0·89) among women aged 25-29 years. Among boys aged 15-19 years anogenital wart diagnoses decreased significantly by 48% (RR 0·52, 95% CI 0·37-0·75) and among men aged 20-24 years they decreased significantly by 32% (RR 0·68, 95% CI 0·47-0·98). After 5-9 years of vaccination, CIN2+ decreased significantly by 51% (RR 0·49, 95% CI 0·42-0·58) among screened girls aged 15-19 years and decreased significantly by 31% (RR 0·69, 95% CI 0·57-0·84) among women aged 20-24 years.
INTERPRETATION: This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects.
FUNDING: WHO, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé.
Correlation between integration of high-risk HPV genome into human DNA detected by molecular combing and the severity of cervical lesions: first results of the EXPL-HPV-002 study.
Ceska Gynekol. 2019; 84(2):84-92 [PubMed] Related Publications
DESIGN: EXPL-HPV-002 is a prospective, open-label, single arm, GCP study conducted at 2 clinical sites in the Czech Republic.
SETTINGS: Investigations centers: Private Gynecology Center, Brno; Gynecological and Obstetrical Clinic, Brno; Genotyping central lab: NRL for Papillomaviruses and polyomaviruses, IHBT, Prague; Histology Central reading: Aeskulab Pathology, Prague; Molecular combing HPV test: Genomic Vision, Bagneux.
METHODS: From June 2016 to May 2018, 688 patients aged 25-65, referred to colposcopy after an abnormal Pap-smear, were enrolled in the study. Among them 60% were found HPV high-risk. The study is divided in two phases: 1. a cross-sectional phase using data collected at first visit (colposcopy images ± histology, pap-smear for HPV genotyping and molecular combing) to study the association between HPV integration status versus colposcopy and histology grades; 2. a longitudinal phase using data collected in follow-up visits: cytology at 6, 18 and 30 months and colposcopy ± histology at 12, 24 and 36 months. A pap-smear collected at 12, 24 and 36 months allows to perform genotyping and molecular combing. HPV integration status is analyzed in comparison with the evolution of lesions, viral clearance and HPV genotype. HPV genotyping and molecular combing were performed on pap-smear samples in central laboratories. Histology data were reviewed by central reading.
RESULTS: The transversal phase of the study is achieved and shows that the HPV integration into the human DNA, monitored by molecular combing, can significantly differentiate normal subjects from women with cervical lesions or cancer.
CONCLUSION: HPV integration into the host genome, monitored by Genomic Visions technology, is a reliable diagnostic biomarker that will greatly help clinicians to improve their medical decision tree.
Knowledge of human papillomavirus and Pap test among Brazilian university students.
Rev Assoc Med Bras (1992). 2019; 65(5):625-632 [PubMed] Related Publications
METHOD: Four hundred and seventy-three university students completed a questionnaire assessing their overall knowledge regarding HPV infection, cervical cancer, and the Pap test. A descriptive analysis is presented, and multivariate analysis using logistic regression identified factors associated with HPV/cervical cancer information.
RESULTS: Knowledge was higher for simple HPV-related and Pap test questions but was lower for HPV interrelations with genital warts and cervical cancer. Being from the health science fields and having high income were factors associated with greater knowledge. Only the minority of the participants recognized all the situations that increased the risk of virus infection presented in the questionnaire.
CONCLUSIONS: These findings highlight the need for educational campaigns regarding HPV infection, its potential as a cervical cancer agent and the forms of prevention available.
Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus.
Nat Commun. 2019; 10(1):2300 [PubMed] Free Access to Full Article Related Publications
Distribution of human papillomavirus infection: a population-based study of cervical samples from Jiangsu Province.
Virol J. 2019; 16(1):67 [PubMed] Free Access to Full Article Related Publications
METHODS: We collected a total of 62,317 cervical cytological specimens from Xuzhou, Nanjing and Suzhou, which represent the northern, middle and southern regions of Jiangsu Province, respectively. All these samples were assigned to 6 groups based on participant age. HPV genotypes tests were performed by using a commercial kit which is designed for the detection of 17 high-risk HPV genotypes and 6 low-risk HPV genotypes.
RESULTS: The overall prevalence of HPV was up to 26.92% in Jiangsu Province. The most common high-risk genotype was HPV52 (5.09%), followed by HPV16, HPV58, HPV53, HPV51 and HPV68. The most prevalent low-risk genotype was HPV81 (2.70%), followed by HPV43, HPV42, HPV6, HPV11 and HPV83. Most infections were caused by HR-HPV, while single-genotype infection occurred more frequently than multiple-genotype infection. Regarding participant age, the overall infection rate of HPV was distributed in a U-shaped manner, with the highest peak in the younger than 20-year-old cohort. Additionally, significant variations were found between different cities, representing different regions of Jiangsu.
CONCLUSIONS: HPV prevalence is high in Jiangsu Province. The prevention of HPV-related diseases is challenging. Given the variation in HPV prevalence between ages groups and regions, a flexible HPV vaccination program, adjusted base on regional infection features, could have a beneficial effect in Jiangsu Province.
Level and factors associated with uptake of human papillomavirus infection vaccine among female adolescents in Lira District, Uganda.
Pan Afr Med J. 2018; 31:184 [PubMed] Free Access to Full Article Related Publications
Methods: a mixed methods approach was employed using a survey among 460 female adolescents. We collected data using an interviewer-administered questionnaire. We interviewed five key informants and conducted ten in-depth interviews. Uptake was defined as completing three doses of the vaccine as per the recommended schedule. Prevalence risk ratios were used as measures of association and were computed using modified poison regression. Content analysis was used for qualitative data.
Results: the mean age of the respondents was 13.97 (SD=1.24). Uptake was at 17.61% (81/460). The factors associated with uptake of HPV vaccine were: attaining ordinary level of education (aPR 1.48, 95%CI 1.11-1.97), positive attitude towards the vaccine (aPR 3.46, 95%CI 1.70-7.02), receiving vaccine doses from different vaccination sites (aPR 1.59, 95% CI 1.10-2.28) and encouragement from a health worker (aPR 1.55, 95%CI 1.15-2.11) or Village Health Team (aPR 3.47, 95%CI 1.50-8.02) to go for the vaccine. Other factors associated with uptake of HPV vaccine included; the existence of community outreaches (aPR 1.47, 95%CI 1.02-2.12), availability of vaccines at vaccination sites (aPR 4.84, 95%CI 2.90-8.08) and receiving full information about the vaccine at the vaccination site (aPR 1.90, 95%CI 1.26-2.85).
Conclusion: HPV vaccine uptake was low in Lira district. Efforts to improve uptake of HPV vaccine should focus on ensuring a consistent supply of vaccines at the vaccination sites, health education aimed at creating a positive attitude towards the vaccine, sensitisation of the adolescents about the vaccine and conducting community outreaches.
Optimisation of Folate-Mediated Liposomal Encapsulated Arsenic Trioxide for Treating HPV-Positive Cervical Cancer Cells In Vitro.
Int J Mol Sci. 2019; 20(9) [PubMed] Free Access to Full Article Related Publications
Cervical cancer - causes and prevention of hpv infections in the opinions of young polish women: a cross-sectional survey.
Wiad Lek. 2019; 72(3):327-335 [PubMed] Related Publications
PATIENTS AND METHODS: Materials and methods: The study was performed using CAWI method based on original questionnaire in electronic form. Online completing of the survey was voluntary and anonymous.
RESULTS: Results: The study was conducted in a group of 2058 women aged 19-33. In total 98.4% of respondents came across the term "cervical cancer", 84.1% knew that cervical cancer could be prevented and the following were identified as the main risk factors: cervical cancer in closest relatives (85.3%) and HPV infection (81.9%). Although according to 82.0% of women HPV infection can be prevented by vaccination, only 18.4% of respondents were vaccinated. The main reason for non-vaccination was lack of knowledge about the availability of the vaccine (41.2%) and high price (32.0%). Of the unvaccinated people, 63.5% declare their will to be vaccinated in the future. Concerning secondary prevention, 98.6% of the respondents admitted that they knew the term "cytological examination", 89.0% indicated that this examination detected the presence of pre-cancerous lesions, and according to 58.4% of respondents, this test should be performed after sexual initiation. Despite the fact that 80.5% of respondents confirmed the fact of beginning sexual activity (44.4% of them had more than 1 partner), 17.1% of the respondents admitted that they didn't go to gynecologist yet. Approximately 84% of respondents believe that the amount of information on cervical cancer prophylaxis and HPV infections currently providing is insufficient.
CONCLUSION: Conclusions: The basic terms regarding primary (vaccination) and secondary (prophylactic tests) prevention of cervical cancer have been widely known. However, the knowledge about specific risk factors, sexual behaviors contributing to HPV infection and, consequently, the ability to self-identify as belonging to higher risk group is insufficient. It is justified to conduct educational activities regarding the assessment of risks related to cervical cancer addressed to young women. Together with education, HPV vaccination and secondary prevention programs require financial support.
Association of the MUTYH Gln324His (CAG/CAC) variant with cervical carcinoma and HR-HPV infection in a Chinese population.
Medicine (Baltimore). 2019; 98(17):e15359 [PubMed] Related Publications
Factors associated with low adherence to cervical cancer follow-up retest among HPV+/ cytology negative women: a study in programmatic context in a low-income population in Argentina.
BMC Cancer. 2019; 19(1):367 [PubMed] Free Access to Full Article Related Publications
METHODS: We used data of women aged 30+ HPV-tested in the JDP and followed until 2018 (n = 49,565). We performed a set of different adjusted logistic regression models. Primary outcomes were re-test attendance and re-test attendance within recommended timeframe. We assessed as covariates age, health insurance status, year of HPV-testing, Pap testing in the past 3 years, HPV-testing modality (clinician-collected (CC) tests/self-collected (SC) tests), and span between HPV-test collection and report of results.
RESULTS: Forty nine thousand five hundred sixty five women were HPV-tested and 6742 had a positive HPV-test. Among HPV+ women, a total of 4522 were HPV+/Cytology negative (67.1%). In total, 3172 HPV+/Cytology negative women (70.1%) had a record of a second HPV test as of March 2018. Only 1196 women (26%) completed the second test within the timeframe. Women with no record of a previous Pap (OR: 0.46, 95% CI: 0.4-0.53, p < 0.001), aged 64+ (OR: 0.46, 95% CI: 0.31-0.68, p < 0.001) were less likely to be retested; while women with clinician-collected samples had higher odds of being re-tested (OR: 1.42, 95% CI: 1.06-1.91, p < 0.001).
CONCLUSIONS: Low re-test rates were found in HPV +/ normal cytology women. Tailored interventions are needed to increase the effectiveness of the screening in this group, especially for those women with characteristics associated to lower attendance.
HPV DNA integration site as proof of the origin of ovarian metastasis from endocervical adenocarcinoma: three case reports.
BMC Cancer. 2019; 19(1):375 [PubMed] Free Access to Full Article Related Publications
CASE PRESENTATION: Two women presented with HPV18 cervical adenocarcinoma. No signs of disease were visible on MRI after treatment. After several years of follow-up, mucinous ovarian tumors were discovered in both patients. Molecular analyses showed that the ovarian lesions were HPV18-positive; indicating a primary cervical origin. A third woman was diagnosed with grade 1 ovarian endometrioid carcinoma with no peritoneal carcinomatosis. Final histological examination and HPV genotyping revealed HPV18-related in situ endometrioid adenocarcinoma in the endocervix and HPV18-related invasive endometrioid adenocarcinoma in the endometrium and both ovaries. Additional molecular analyses performed in two patients identified the same HPV integration sites in both the ovarian and cervical tumors, confirming that the ovarian mass was a metastasis from the cervical adenocarcinoma.
CONCLUSION: We report three new cases of ovarian neoplasia in which the diagnosis of metastasis from cervical cancer was supported by the same HPV genotype and the same integration site in the paired cervical and ovarian tumors. To our knowledge, this is the first report of molecular evidence of the cervical origin of an ovarian metastasis. HPV screening should be performed in ovarian tumors for all patients with history of cervical neoplasia.
The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up.
Gynecol Oncol. 2019; 153(3):521-529 [PubMed] Related Publications
METHODS: Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug.
RESULTS: Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions.
CONCLUSIONS: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.
Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study.
BMJ. 2019; 365:l1161 [PubMed] Free Access to Full Article Related Publications
DESIGN: Retrospective population study, 1988-96.
SETTING: National vaccination and cervical screening programmes in Scotland.
PARTICIPANTS: 138 692 women born between 1 January 1988 and 5 June 1996 and who had a smear test result recorded at age 20.
MAIN OUTCOME MEASURES: Effect of vaccination on cytology results and associated histological diagnoses from first year of screening (while aged 20), calculated using logistic regression.
RESULTS: 138 692 records were retrieved. Compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 showed an 89% reduction (95% confidence interval 81% to 94%) in prevalent cervical intraepithelial neoplasia (CIN) grade 3 or worse (from 0.59% (0.48% to 0.71%) to 0.06% (0.04% to 0.11%)), an 88% reduction (83% to 92%) in CIN grade 2 or worse (from 1.44% (1.28% to 1.63%) to 0.17% (0.12% to 0.24%)), and a 79% reduction (69% to 86%) in CIN grade 1 (from 0.69% (0.58% to 0.63%) to 0.15% (0.10% to 0.21%)). Younger age at immunisation was associated with increasing vaccine effectiveness: 86% (75% to 92%) for CIN grade 3 or worse for women vaccinated at age 12-13 compared with 51% (28% to 66%) for women vaccinated at age 17. Evidence of herd protection against high grade cervical disease was found in unvaccinated girls in the 1995 and 1996 cohorts.
CONCLUSIONS: Routine vaccination of girls aged 12-13 years with the bivalent HPV vaccine in Scotland has led to a dramatic reduction in preinvasive cervical disease. Evidence of clinically relevant herd protection is apparent in unvaccinated women. These data are consistent with the reduced prevalence of high risk HPV in Scotland. The bivalent vaccine is confirmed as being highly effective vaccine and should greatly reduce the incidence of cervical cancer. The findings will need to be considered by cervical cancer prevention programmes worldwide.
Management of ASC-US/HPV positive post-menopausal woman.
Virol J. 2019; 16(1):39 [PubMed] Free Access to Full Article Related Publications
RESULTS: In the first arm the HPV test had an SE of 94%, an SP of 68%, NPV of 99%, and PPV of 28%. The PPV is very low because of the elevated percentage of false positives that the HPV test gave (71%). In the second arm the HPV test maintained its high SE (100%), an SP of 74%, a NPV of 100%, and a PPV of 43%. The use of estrogen increased the specificity of the test.
CONCLUSION: It is important to say that the second arm indicates the use of local estrogen therapy only for ASCUS/HPV positive postmenopausal women. Therefore, the HPV test should be used as the first diagnostic possibility in cases of ASCUS in post-menopausal women, associating local estrogen therapy only with HPV positive women.
HPV testing for cervical cancer screening: technical improvement of laboratory logistics and good clinical performance of the cobas 6800 in comparison to the 4800 system.
BMC Womens Health. 2019; 19(1):47 [PubMed] Free Access to Full Article Related Publications
METHODS: We conducted a comparison study, according to the international guidelines, nested within the organized population-based cervical screening program, between the cobas 4800 and 6800 systems (Roche Diagnostics), to evaluate accuracy and reproducibility of HPV test results and laboratory workflow. In Italy implementation of HPV cervical screening is under way on a regional basis; in Veneto it started in June 2015, following a piloting phase; the assay in use in the three centralized laboratories is the cobas 4800 HPV test, run on the cobas 4800 system. Comparison of HPV results with a new version of the assay (cobas 6800/8800 HPV) run on the cobas 6800 system, and intra- and inter-reproducibility analyses have been conducted in samples collected in PreservCyt medium (Hologic) from women without and with a subsequent diagnosis of high-grade lesion.
RESULTS: Samples from women older than 30 years attending organized cervical cancer screening were used. Clinical sensitivity and specificity were evaluated on 60 cases and 925 controls, respectively; intra-laboratory reproducibility and inter-laboratory agreement by the 6800 system were evaluated on 593 and 460 specimens, respectively. Our results showed a very high agreement (> 98%) for overall qualitative results between the two systems; clinical sensitivity and specificity of the HPV assay run on 6800 were non-inferior to those of the HPV assay run on 4800 (p = 0,0157 and p = 0,0056, respectively, at the recommended thresholds of 90 and 98%); kappa values of 0.967 and 0.969 were obtained for intra- and inter-laboratory reproducibility analyses in the 6800 system. The 6800 platform displayed several technological improvements over the 4800 system, with higher throughput and laboratory productivity, and lower operator's hands-on time.
CONCLUSIONS: The new cobas 6800/8800 HPV assay run on the 6800 instrument is suitable for use in large centralized laboratories included within population-based cervical cancer screening programs.
The combined impact of implementing HPV immunisation and primary HPV screening in New Zealand: Transitional and long-term benefits, costs and resource utilisation implications.
Gynecol Oncol. 2019; 152(3):472-479 [PubMed] Related Publications
METHODS: An extensively validated model of HPV transmission, vaccination, natural history and cervical screening ('Policy1-Cervix') was utilised to simulate a transition from three-yearly cytology for women 20-69 years to five-yearly HPV screening with 16/18 genotyping for women 25-69 years, accounting for population growth and the impact of HPV immunisation. Cervical cancer rates, resources use (test volumes), costs, and test positivity rates from 2015 to 2035 were estimated.
FINDINGS: By 2035, the transition to HPV screening will result in declines in cervical cancer incidence and mortality rates by 32% and 25%, respectively, compared to 2018. A potentially detectable 5% increase in cervical cancer incidence due to earlier detection is predicted for the year of transition. Annual numbers of women screened will fluctuate with the five-year screening interval. Cytology volumes will reduce by over 80% but colposcopy volumes will be similar to pre-transition rates, and program costs will be reduced by 16%. A 9% HPV test positivity rate is expected in the first round of HPV screening (2019-2023), with 2.7% of women referred for colposcopy. Transitioning from cytology to primary HPV cervical screening could avert 149 cancer cases and 45 deaths by 2035.
CONCLUSION: Primary HPV screening and vaccination will reduce cervical cancer and resources use. A small transient apparent increase of invasive cancer rates due to earlier detection may be detectable at the population level, reflecting the introduction of a more sensitive screening test. These findings can be used to inform health services planning and public communications surrounding program implementation.
Human Papillomavirus Status in Primary Lesions and Pelvic Lymph Nodes and Its Prognostic Value in Cervical Cancer Patients with Lymph Node Metastases.
Med Sci Monit. 2019; 25:1894-1902 [PubMed] Free Access to Full Article Related Publications
HPV infections and cytologic abnormalities in vaccinated women 21-34 years of age: Results from the baseline phase of the Onclarity trial.
Gynecol Oncol. 2019; 153(2):259-265 [PubMed] Related Publications
METHODS: The Onclarity trial enrolled 33,858 subjects ≥21 years who were screened with cytology and the BD Onclarity HPV Assay. HPV positive women or those with cytologic abnormalities underwent colposcopy and biopsy. The prevalence of HPV, cytologic abnormalities, and ≥CIN2 was compared in a subset of 14,153, vaccinated and unvaccinated women, 21-34 years. Results were compared by vaccination status; Mantel-Haenszel analysis was performed to determine the association between vaccination status and prevalence, adjusting for age.
RESULTS: The prevalence of overall HPV, HPV16, 18, 31, and 33/58 were all lower in vaccinated women for each age group; a significant difference (p < 0.001) was observed in vaccinated women for all ages combined. Cytologic low-grade squamous intraepithelial lesion (LSIL) or worse was lower in vaccinated women (p = 0.021), as was ≥CIN2 prevalence associated with HPV 16 or 18 (p = 0.011).
CONCLUSIONS: Women with a prior history of HPV vaccination have a lower prevalence of any high-risk HPV, HPV 16, 18, 31, and 33/58; a cytology result of ≥LSIL, and ≥CIN2 associated with HPV 16/18 compared to unvaccinated women. A lower HPV prevalence in older, vaccinated women suggests that "catch-up" vaccination provides benefit.
Nanobody against the E7 oncoprotein of human papillomavirus 16.
Mol Immunol. 2019; 109:12-19 [PubMed] Related Publications
Study on the relationship between methylation status of HPV 16 E2 binding sites and cervical lesions.
Clin Chim Acta. 2019; 493:98-103 [PubMed] Related Publications
METHODS: Methylation status of the four E2BSs in 43 clinical cervical samples with HPV 16 infection was quantitatively detected using pyrosequencing. Meanwhile, Quantivirus® HPV E6/E7 RNA 3.0 assay (bDNA) was used to detect E6/E7 mRNA levels in the corresponding specimens.
RESULTS: Our results showed that methylation status of E2BS1, 2 and 4 sites in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer were significantly higher than that of asymptomatic HPV 16 infection and low-grade squamous intraepithelial lesions (LSIL) (all P < .05). Furthermore, methylation status of HPV 16 E2BS1 and 2 was positively correlated with E6/E7 mRNA levels (r
CONCLUSIONS: The methylation status of E2BS1 and 2 may have utility as diagnostic markers for the severity of cervical lesions in the future.
Educating Latinas about cervical cancer and HPV: a pilot randomized study.
Cancer Causes Control. 2019; 30(4):375-384 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
METHODS: Three active educational intervention arms were developed: a fotonovela, a radionovela, and a digital story. A pilot randomized controlled trial of 160 Latinas was conducted to assess the effectiveness of the intervention arms in increasing knowledge of cervical cancer and HPV and intention to be screened for cervical cancer compared to an attention control group (flu vaccination).
RESULTS: Women in all three treatment arms significantly increased knowledge about cervical cancer compared to control arm (p = 0.02). Knowledge about cervical cancer screening also increased in the active arms compared to control (p = 0.0003). Knowledge of HPV risk also increased relative to the control (p = 0.0001). There were no significant differences between the intervention arms in increased knowledge of cervical cancer or cervical cancer screening (p = 0.57 and 0.16, respectively).
DISCUSSION: This study supported the use of small media interventions in narrative education form as effective in increasing knowledge and intention to be screened for cervical cancer. The three culturally relevant interventions, built on qualitative data, were all successful in increasing knowledge.
Prevalence and nonsexual transmission of human papilloma virus (HPV) in the adolescence girls from rural area of Maharashtra state, India.
Indian J Cancer. 2018 Oct-Dec; 55(4):336-339 [PubMed] Related Publications
METHOD: Menstrual pads were collected from the women of age group years to find out the presence of HPV and whether it can be used as a cervical cancer screening tool. The results of the said study have been published in the European Journal of Cancer Prevention. During this study, menstrual pads of the daughters of participating women were collected to see the nonsexual transmission of HPV. After conducting the health education and obtaining the informed consent, we interviewed 57 mothers (age group 30-50, married, sexually active) and daughters [age group 12-18, unmarried (not exposed to sex)] from the rural area of Pune district of Maharashtra state, India. The menstrual pads were collected and transported to Mumbai for polymerase chain reaction (PCR) testing. HPV testing was carried out by PCR.
RESULTS: Out of 57, 28 (49%) daughters and 23 (40.4%) mothers provided menstrual pad. Out of 23 mothers, one was HPV positive [4.3%: 95% confidence interval (CI) 0.2-23.0] and out of 28 girls, 3 (10.7%: 95% CI 2.0-33.0) were HPV positive. The daughter, whose mother was HPV positive, had negative result for HPV.
CONCLUSION: The HPV prevalence in adolescence girls was 10.7%. There may be other nonsexual medium that might have caused HPV in adolescence girls, which needs further research.
Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies.
BMC Public Health. 2019; 19(1):235 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
METHODS: A budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25-64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2-3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer's perspective.
RESULTS: HPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (- 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (- 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years.
CONCLUSION: The results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.
Prevalence of human papillomavirus and subtype distribution in male partners of women with cervical intraepithelial neoplasia (CIN): a systematic review.
BMC Infect Dis. 2019; 19(1):192 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
METHODS: We conducted a systematic review of the literature by Medline and Google Scholar databases using the terms "Human Papillomavirus" or "HPV" plus "men" or "male partners" or "women with CIN". We included original published English-language articles published from 1/1/2000 until 1/1/2018 that had screened male partners of women with CIN using HPV DNA testing. We excluded studies that they overlapped with other included studies or were unrelated to the study subject.
RESULTS: We included a total of 12 publications, which reported the prevalence of HPV in free-clinical signs male partners of women with CIN. The largest proportion of the studies were from South America (seven studies), and the rest from Europe. The mean age of participants was 35.18 + - 3.47 years. HPV prevalence ranged from 12.9 to 86%; the total HPV prevalence among the studies was 49.1%, while ten out twelve studies (83.3%) demonstrated prevalence > 20%. Between the studies, the distribution of HPV subtypes varied on the basis of the method used, on the population and on the geographic region. A great variety of subtypes were detected, including 6, 11, 16, 18, 31, 33, 40, 42, 45, 51, 52, 53, 54, 56, 57, 58, 59, 61, 62, 66, 68, 81 and 83. In six studies the HPV 16 was the most frequent, while in two others the HPV 6 and HPV 83.
CONCLUSIONS: Until now, there are not precise screening or surveillance guidelines for the management of partners of women with CIN. This population is frequently colonized by various HPV subtypes and therefore need to be screened in an effort to reduce the infection in both sexes. The screening test could include detection/identification of HPV subtypes by a molecular assay, followed by peniscopy only in the positive cases.
hrHPV prevalence and type distribution in rural Zimbabwe: A community-based self-collection study using near-point-of-care GeneXpert HPV testing.
Int J Infect Dis. 2019; 82:21-29 [PubMed] Article available free on PMC after 01/04/2020 Related Publications
DESIGN AND METHODS: To determine hrHPV prevalence and type distribution in Zimbabwe we implemented a community-based cross-sectional study of self-collected cervicovaginal samples with hrHPV screening using near-point-of-care Cepheid GeneXpert HPV.
RESULTS: The hrHPV prevalence was 17% (112/643); 33% (41/123) vs. 14% (71/520) among HIV-1-positive and -negative participants, respectively (p=2.3E-07). Typing via Xpert HPV showed very good overall agreement (77.2%, kappa=0.698) with the Seegene Anyplex II HPV HR Detection kit. The most common types were HPV16, HPV18, HPV35, HPV52, HPV58, HPV68, HPV18, and HPV51, each of which appeared in 14-20% of infections. 37% (28/76) of women with positive cytology results (ASCUS+) had a type not included in the basic vaccine and 25% (19/76) had a type not currently in the nine-valent vaccine.
CONCLUSIONS: hrHPV type distribution includes less common high-risk types in rural Zimbabwe. The distribution and carcinogenicity of hrHPV type distribution should be considered during screening assay design, program development, as well as vaccine distribution and design.
Risk Categorization with Different Grades of Cervical Pre-Neoplastic Lesions - High Risk HPV Associations and Expression of p53 and RARβ
Asian Pac J Cancer Prev. 2019; 20(2):549-555 [PubMed] Related Publications
Cost-Utility of a Two-Dose Human Papillomavirus Vaccination Programme Added to Cervical Cancer Screening Compared with Cervical Cancer Screening Alone in Korea
Asian Pac J Cancer Prev. 2019; 20(2):425-435 [PubMed] Related Publications
Comparison of Colposcopic Biopsy Results of Patients Who have Cytomorphological Normal but HPV 16-18 or Other High-Risk HPV Subtypes Positive
Asian Pac J Cancer Prev. 2019; 20(2):417-420 [PubMed] Related Publications
Detection and genotyping of HPV-DNA through different types of diagnostic platforms in liquid-based cervical-cytology samples.
Pathologica. 2018; 110(4):294-301 [PubMed] Related Publications
Methods: The study is based on a group of patients which went to their private gynecologist in a contest of opportunistic screening. The vial used in the examined population has been EASYPREP
Results: We have examined 1284 samples of women aged 16 to 73 years: 1125 have been tested using HC2 procedure, 272 samples with Onclarity method, 159 with Xpert
Discussion: The present study highlights the following: 1) Positive results' percentage for high-risk HPV-DNA genotypes, deriving from the three diagnostic platforms used and with the same vial to collect and store samples, does not significantly vary on the basis of the type of equipment and it is congruent with the Italian percentage already detected during organized screening programs. 2) Even the molecular diagnostic approach could give false negative results, preventing the detection in the screened population of cervical HPV-related lesions and theoretically endangering women to develop "interval cancer". 3) In the population examined, genotype 16 has been the most expressed, whereas genotype 18 was among the less frequently detected. Other genotypes often noticed have been: 56-59-66 (Onclarity P3 group), 31, 51 and 35-39-68 (Onclarity P2 group). This remark emphasizes the importance of HPV infection and genotypes distribution's continuous monitoring, considering that HPV-vaccines planned in Italy in the "National vaccination prevention program 2017-2019" are not specific for the majority of these genotypes. 4) The necessity to improve the screening program to identify cervical carcinomas and pre-neoplastic cervical lesions is remarked by the detection during HPV-test of possible coinfection (present at least in 8,76% of our records). In fact, the risk of development of cervical cancer might be associated with type-specific interactions between genotypes in multiple infections and, in addition, other genotypes, not targeted by quadrivalent HPV-vaccine, can increase the risk of cervical carcinoma. 5) As there's a different combination of HPV-genotypes in diagnostic categories used by the HPV screening platforms, it's important that anyone who is in charge of this diagnostic analysis promotes among clinicians the adequate rendition of the laboratory's data in the patient records, reporting both the diagnostic result and the method through which it has been obtained.
Prevalence of oncogenic Human papillomavirus and genetic diversity in the L1 gene of HPV16 HPV 18 HPV31 and HPV33 found in women from Vojvodina Province Serbia.
Biologicals. 2019; 58:57-63 [PubMed] Related Publications