Human Papillomavirus DNA Screening Research Articles

Cervical cancer in Malaysia.

Cervical cancer is preventable due to effective screening to detect pre-malignant lesion, and vaccination against its causative organism namely human papillomavirus (HPV). This review article described current situation of cervical cancer in Malaysia. There is decreasing cervical cancer incidence in the country, with age-standardized rate of 10.3, versus 14.1 and 7.5 per 100 000 for worldwide and high-income countries, respectively. School-based HPV vaccination is part of national immunization since 2010, with yearly coverage rate of 83%-91%. The figure declined during coronavirus disease-19 pandemic due to scarce vaccine supply and movement-control order, resulting in about 500 000 students missing their course, with catch-up program currently onboard. Opportunistic cervical screening program started in 1960s with cervical smear cytology, which is succeeded by HPV DNA screening since 2020. Cervical cytology remains indispensable screening method in healthcare facility without access to HPV test kit, and used to triage high-risk HPV positive with abnormal cytology that require urgent colposcopy. Computed tomography is the main imaging modality to assess local and distal extent of cervical cancer. Primary surgical treatment for early-stage cancer is performed by trained gynecologic oncologist, with long waiting list for radiation therapy in locally advanced disease due to limited available public facility. There is restricted access to targeted therapy due to high treatment cost. In conclusion, Malaysia is heading toward cervical cancer elimination through rigorous investment in primary and secondary prevention, and increase in public engagement with the support of government policy enforcement.

Investigation of Human Papillomavirus (HPV) Frequency and Genotype Analysis in Cervical Samples

Aim: Human Papillomaviruses (HPVs) are double-stranded DNA viruses belonging to the Papillomaviridae family. There is ample evidence demonstrating the association of Human Papillomavirus (HPV) with cervical carcinoma. This study aimed to investigate the presence of HPV DNA in cervical swab samples and determine the HPV genotypes in positive samples.
 Materials and Methods: The three-year results of cervical swab samples sent to the Medical Microbiology Laboratory of Afyonkarahisar Health Sciences University Faculty of Medicine Hospital for screening for HPV DNA presence between January 1, 2020, and December 31, 2022, were retrospectively evaluated in this study. HPV genotyping was performed using the cobas 4800 (cobas® x480) fully automated system (Roche Diagnostics, Indianapolis, USA) for extraction, and the samples were analyzed using the Real-time PCR (cobas® z 480) system following the manufacturer's instructions. 
 Results: HPV-DNA was detected in 415 out of a total of 4960 patients (8.4%), while 4545 (91.6%) tested negative. Evaluation of HPV positivity revealed that the highest positivity rates were observed in HR-HPV at 68%, HPV 16 at 17.3%, and HPV 16 combined with HR-HPV at 8.2%. HPV-DNA positivity was highest at 38% in the 35-44 age group, while it was lowest at 3.4% in patients under 25 years old. 
 Conclusion: Vaccination programs, alongside screening programs, will serve to restrict the spread of infection in at-risk populations and prevent HPV-related cancers. It is believed that nationwide HPV DNA screening studies and vaccination programs targeting HPV infections will be highly effective in reducing the prevalence of cervical cancer.

A pilot study on salivary HPV DNA detection to monitor active disease from patients with recurrent respiratory papillomatosis

PurposeRecurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-related disease affecting the upper airway and saliva could be an important non-invasive sampling source for viral screening and clinical monitoring. We investigated whether HPV DNA could be detected in saliva (cellular pellets and supernatant) from RRP patients and influence on clinical manifestation of the disease. Materials and methodsIn this pilot study, saliva samples from 14 RRP patients were obtained in preoperative condition (n = 7) and in disease-free interval (DFI; n = 7). Healthy donors (n = 14) were also included. HPV DNA was investigated by polymerase chain reaction (PCR)-based assays. ResultsFrom cellular pellets, HPV-positive saliva was only detected from preoperative collections (5/7; 71.4 %) and showed a mean cycle threshold (Ct) value of 24.33 (±1.25), whereas all patients in DFI were HPV-negative (Ct ≥ 32.16), revealing significant difference between these two clinical moments (p = 0.021). Patients in DFI and healthy donors showed similar Ct values. From saliva supernatant, detectable HPV cell-free DNA (cfDNA) occurred in 42.9 % (3/7) and 57.1 % (4/7) of preoperative collections using the commercial cfDNA kits from Norgen and Qiagen, respectively. Salivary cfDNA size distribution obtained by TapeStation analysis showed a predominant size range of 150 to 400 bp in both patients and healthy controls, corresponding to mononucleosomal and dinucleosomal fragments. ConclusionsIn conclusion, HPV DNA screening in saliva (both cellular pellets and cfDNA) may have clinical utility to monitor active disease of RRP patients.

Development and validation of real-time recombinase polymerase amplification-based assays for detecting HPV16 and HPV18 DNA.

Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. Persistent human papillomavirus (HPV) infection is the principal cause of cervical cancer, with HPV16 and HPV18 accounting for about 70% of cases worldwide. Cervical screening is an effective secondary measure for preventing cervical cancer. Testing for HPV DNA is becoming increasingly important in cervical cancer screening. The existing PCR-based HPV detection technology has several disadvantages: the assays are time-consuming, and sophisticated equipment is required to control the temperature cycles. These drawbacks have led to the development of detection technologies based on isothermal amplification. Here, we present real-time recombinase polymerase amplification (RPA-exo)-based assays for single genotyping of either the E7 or the L1 segment of HPV16 or HPV18. These assays were highly sensitive, able to detect HPV in all clinical samples with Ct values below 34, and yielded results within 25 min. A dual-detection system capable of detecting both HPV16 and HPV18 in a single reaction was also developed based on the L1 gene. It has a limit of detection of approximately 10,000 copies of each genotype per reaction. The assays were validated with DNA extracted from 36 biopsy specimens and 42 exfoliated cell samples from 43 patients with cervical lesions at different stages. The RPA-exo system is a promising clinical detection platform with the advantages of yielding results rapidly and operating at a constant temperature, while being cost-effective and easy to use. IMPORTANCE HPV DNA screening is an effective approach for the prevention of cervical cancer. The novel real-time recombinase polymerase amplification-based HPV detection systems we developed constitute an improvement over the HPV detection methods currently used in clinical practice and should help to extend cervical cancer screening in the future, particularly in point-of-care test settings.

Cost-effectiveness of artificial intelligence-assisted liquid-based cytology testing for cervical cancer screening in China

The 2021 World Health Organization (WHO) guidelines for cervical cancer screening recommend human papillomavirus (HPV) DNA or mRNA testing. Artificial intelligence (AI)-assisted liquid-based cytology (LBC) systems also have the potential to facilitate rapid scale-up of cervical cancer screening. We aimed to evaluate the cost-effectiveness of AI-assisted LBC testing, compared with the manual LBC and HPV-DNA testing, for primary cervical cancer screening in China. We developed a Markov model for a cohort of 100,000 women aged 30 years over a lifetime to simulate the natural history of cervical cancer progression. We evaluated the incremental cost-effectiveness ratios (ICER) of 18 screening strategies (a combination of the three screening methods with six screening frequencies) from a healthcare provider's perspective. The willingness-to-pay threshold (US$30,828) was chosen as three times the Chinese per-capita gross domestic product in 2019. Univariate and probabilistic sensitivity analyses were performed to examine the robustness of the results. Compared with no screening, all 18 screening strategies were cost-effective, with an ICER of $622-24,482 per quality-adjusted life-year (QALY) gained. If HPV testing after scaling up to population level screening costs $10.80 or more, screening once every 5 years using AI-assisted LBC would be the most cost-effective strategy with an ICER of $8790/QALY gained compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. Its probability of being cost-effective was higher (55.4%) than other strategies. Sensitivity analyses showed that the most cost-effective strategy would become AI-assisted LBC testing once every 3 years if the sensitivity (74.1%) and specificity (95.6%) of this method were both reduced by ≥10%. The most cost-effective strategy would become HPV-DNA testing once every 5 years if the cost of AI-assisted LBC was more expensive than manual LBC or if the HPV-DNA test cost is slightly reduced (from $10.8 to <$9.4). AI-assisted LBC screening once every 5 years could be more cost-effective than manually-read LBC. Using AI-assisted LBC could have comparable cost-effectiveness to HPV DNA screening, but the relative pricing of HPV DNA testing is critical in this result. National Natural Science Foundation of China, National Key R&D Program of China.

Stepped Behavioral and Biological Screening for Oral Oncogenic HPV DNA in Middle-aged and Elderly Adults: A Feasibility Study.

Novel preventive interventions are needed to address the rising incidence of HPV+ OPC. In this feasibility study, we characterized barriers to a two-step, behavioral and biological screening program for oral oncogenic HPV infection, an intermediate outcome for HPV+ OPC.

Dual-enzyme cascade amplification electrochemical biosensor for human papillomavirus based on DNA nanoflower structure

The lack of large-scale human papillomavirus (HPV) DNA screening is a major contributor to the high incidence and mortality of cervical cancer in economically undeveloped areas. The development of sensitive, rapid, and low-cost screening techniques is urgently needed. Here, DNA nanoflowers encapsulating glucose oxidase and horseradish peroxidase (GHDFs) were synthesized by one-pot rolling circle amplification, and then the GHDFs were used as the cargo of DNA hydrogel and applied for HPV DNA detection. When target DNA was present, the DNA hydrogel cross-linking structure was disrupted, releasing GHDFs, which then catalysed the oxidation of glucose and tetramethylbenzidine in a cascade, generating a significant electrical signal. Signal intensity had a linear relationship with the logarithm of target DNA concentration in the range of 10 fM-1 nM with a detection limit of 3.76 fM. The detection time of the proposed biosensor was 25 min, which was suitable for large-scale HPV DNA screening in economically underdeveloped areas and provides a blueprint for the detection of other DNA of interest.

Age-specific prevalence and genotype distribution of human papillomavirus in women from Northwest China.

Human papillomavirus (HPV) is the leading cause of cervical cancer with more than 200 genotypes. Different genotypes have different potentials in causing premalignant lesions and cervical cancers. In this study, we investigated the age-specific prevalence and genotype distribution of HPV genotypes in Northwest China. We recruited 145,918 unvaccinated women from Northwest China for population-based HPV DNA screening test during June 2015 to December 2020. And a lab-based test was performed for each volunteer by flow fluorescent technology to identify the genotypes of HPV. The overall infection rate of HPV was 22.97%. With the participants divided into 12 groups according to age, a bimodal curve of infection rate was obtained. And the two peaks appeared in the younger than 20 group and 61-65 group, respectively. The five most common HPV genotypes included HPV 16, 58, 52, 53 and 61 in all participants, which were in descending order of frequency. Among women younger than 25 years old, HPV 6 and 11 were more common and even higher than some genotypes mentioned above. Among women older than 65 years old, HPV 18 and 66 were more common than or as high as the six most common genotypes in all populations. Additionally, the distribution of single and multiple infections in each age group was also different. The baseline prevalence and genotype distribution of HPV in Northwest China was uncovered for the first time. Age was related to the epidemiology of different HPV genotypes. All the results would be of great significance for future healthcare services.

Rationale and design of the Prevent Anal Cancer Self-Swab Study: a protocol for a randomised clinical trial of home-based self-collection of cells for anal cancer screening

IntroductionSquamous cell carcinoma of the anus is a common cancer among sexual minority men, especially HIV-positive sexual minority men; however, there is no evidenced-based national screening protocol for detection of...

Negative Roche cobas HPV testing in cases of biopsy-proven invasive cervical carcinoma, compared with Hybrid Capture 2 and liquid-based cytology

The objective of this study was to conduct a retrospective analysis of results of cytology and Roche cobas (RC) and Hybrid Capture 2 (HC2) human papillomavirus (HPV) screening tests in cases of biopsy-proven invasive cervical carcinoma. The clinical data were obtained at a university hospital in New York, NY, between 2004 and 2017. Results of cytology, reported per Bethesda classification system, and HPV screening in 177 identified cases with cytology and biopsy-proven diagnosis of cervical carcinoma were included in the analysis. Two cohorts were analyzed. Of the 177 identified cases, cotesting was performed for 100 patients. Among these 100, cotesting screening results would not trigger immediate colposcopy in 6%; HPV screening results were reported as negative in 16% (16% of all RC, 16% of all HC2, 16% total) and, if HPV was the only screening modality, would not trigger a colposcopy. Of the 177 total cases, 128 patients underwent cytology screening prior to biopsy, with a cytology diagnosis that, alone, would not trigger immediate colposcopy in 14%. The HPV DNA screening and cytology screening alone were negative for 16% and 14%, respectively, of patients with biopsy-proven diagnoses of invasive carcinoma of cervical origin, without a significant difference in failure rates between cytology, HC2, and RC. The cotesting approach had a significantly lower failure rate (6%) compared with the 2 other screening modalities alone.

The Utility of Urine-Based Sampling for Cervical Cancer Screening in Low-Resource Settings.

Background:WHO has recommended Visual Inspection with Acetic acid (VIA) or Human Papillomavirus (HPV) DNA testing if feasible, for cervical cancer screening in low income countries. However, the number of women undergoing screening is very low as a result of limited information, inadequate infrastructure and invasive nature of sampling. Methods:A cross sectional study was carried out comparing HPV DNA detection by Polymerase Chain Reaction (PCR) in paired cervical and urine samples procured from histologically confirmed cervical cancer cases. Results:Amongst the samples collected from 114 cervical cancer cases, HPV DNA was tested positive in cervical samples of 89 (78.1%) and urine samples of 55 (48.2%) patients. The agreement between the two sampling methods was 66.7% and the kappa value was 0.35 indicating a fair agreement. The sensitivity of HPV detection using urine samples was 59.6% (95% confidence interval 49.16%-69.15%) and the specificity was 92% (95% confidence interval 75.0%-97.8%). Conclusion:Even though not acceptable as an HPV DNA screening tool due to low sensitivity, the urine sampling method is inexpensive and more socially acceptable for large epidemiological surveys in developing countries to estimate the burden.

Self-Collection and Molecular Diagnosis for Detection of Human Papillomavirus: Why Incorporate It?

Cervical cancer, the third cause of death by cancer among Brazil's women, is associated with human papillomavirus (HPV) infection. In some countries of South America, North America, Europe, and Oceania, initial screening for HPV DNA and subsequent follow-up with HPV-positive patients using colposcopy and cytological testing are used as preventative measures. For HPV DNA detection, it is necessary to obtain cervical cells by conventional clinical collection method or self-collection of the cells that flake off from the uterine cervix and vaginal canal. Self-collection has been shown to be a viable option for obtaining samples and is a less invasive method that is more accepted by women. Thus, it can potentially decrease the limitations of the conventional clinical collection methods. The efficiency of the self-collection method aligned with the implementation of HPV molecular testing, if adopted by public and private health care systems, may extend the reach of current cervical cancer prevention efforts. In addition, considering all phases from triage to treatment, this method may reduce health care costs and the time spent by patients and health care teams to conduct examinations and collect samples.

Two-Year Results of Community-Based Screening Program for Human Papilloma Virus DNA in Çorum Province.

The Turkish Ministry of Health started a community-based screening program using Human Papilloma Virus (HPV) DNA in 2014. In our study, we aimed to investigate the results of this survey in Çorum province between the years of 2016-17 to determine the shortcomings and deficiencies in practice. All of the women between the ages of 30 and 65 years who had undergone High risk HPV DNA screening in Çorum province between 2016 and 2017 were included in the study. High risk HPV types were divided into three categories as type 16, 18 and others. The target group of patients to be screened were compared with the numbers reached in the survey. After colposcopic biopsy, the clinicopathological correlation of the patients who underwent colposcopic biopsy was determined via pathology reports. HPV DNA was detected in 817 women (3.5%). HPV types 16, 18 and others were found to be positive in 216, 32 and 569 individuals, respectively. Cervical biopsy was performed with colposcopy in 212 (26%) women. As the result of colposcopy, LSIL and HSIL were detected in 63 and 56 patients, respectively. 34.5% of patients with the diagnosis of any kind of dysplasia received treatments. It was determined that 44% of HPV DNA-positive patients were not subjected to the appropriate processes according to the national guidelines. This shows that despite the screening, the desired therapeutic effect could not be achieved.

Cost-Effectiveness of Cervical Cancer Screening in Women Living With HIV in South Africa: A Mathematical Modeling Study.

Women with HIV face an increased risk of human papillomavirus (HPV) acquisition and persistence, cervical intraepithelial neoplasia, and invasive cervical cancer. Our objective was to determine the cost-effectiveness of different cervical cancer screening strategies among women with HIV in South Africa. We modified a mathematical model of HPV infection and cervical disease to reflect coinfection with HIV. The model was calibrated to epidemiologic data from HIV-infected women in South Africa. Clinical and economic data were drawn from in-country data sources. The model was used to project reductions in the lifetime risk of cervical cancer and incremental cost-effectiveness ratios (ICERs) of Pap and HPV DNA screening and management algorithms beginning at HIV diagnosis, at 1-, 2-, or 3-year intervals. Strategies with an ICER below South Africa's 2016 per capita gross domestic product (US$5270) were considered "cost-effective." HPV testing followed by treatment (test-and-treat) at 2-year intervals was the most effective strategy that was also cost-effective, reducing lifetime cancer risk by 56.6% with an ICER of US$3010 per year of life saved. Other cost-effective strategies included Pap (referral threshold: HSIL+) at 1-, 2-, and 3-year intervals, and HPV test-and-treat at 3-year intervals. Pap (ASCUS+), HPV testing with 16/18 genotyping, and HPV testing with Pap or visual triage of HPV-positive women were less effective and more costly than alternatives. Considering per capita gross domestic product as the benchmark for cost-effectiveness, HPV test-and-treat is optimal in South Africa. At lower cost-effectiveness benchmarks, Pap (HSIL+) would be optimal.

Concordant Oral and Vaginal Human Papillomavirus Infection in the United States.

Human papillomavirus (HPV) is a common infection in adults, with tropism for sites in the head and neck and the genital tracts. To date, few studies have addressed concurrent infection in these sites. To understand the prevalence, characteristics, and concordance of HPV infections in the oral and vaginal regions. This study was a retrospective analysis of cross-sectional survey data from the National Health and Nutrition Examination Survey, 2009-2012. The database was reviewed for all women aged 18 to 69 years with available oral and vaginal HPV DNA screening data. The study was performed from August 1, 2014, to November 1, 2014. Data analysis was performed from November 1, 2014, to June 30, 2015. Logistic regression models were constructed to identify factors associated with infection. Covariates for multivariate analysis included age, income to poverty ratio, number of prior sexual partners, number of prior oral sex partners, and having recent oral sex partners. Dual infection was defined as having an infection of any serotype in both the oral and vaginal HPV regions. Concordant infection was defined as an infection of matching serotype in both locations. A total of 3463 women were identified (mean [SD] age, 37.5 [12.1] years). Racial distribution was 1341 white (38.7%), 786 black (22.7%), 554 Mexican American (16.0%), 378 other Hispanic (10.9%), and 404 self-identified as other (11.7%). Vaginal HPV infection was present in 1586 (45.2%) and oral HPV infection in 141 (4.1%). Dual infection was identified in 107 (3.0%) of all patients, and concordant infection was observed in 41 (1.1%). The prevalence of dual infection was 75.9% in those with oral infection and 6.8% in those with vaginal infection. On multivariate analysis, age (30-50 years) and higher income to poverty ratios had negative associations with dual and concordant infections. A new sexual partner within the last year was positively associated with dual infection (odds ratio, 2.28; 95% CI, 1.03-5.02; P = .04). More than 2 oral sex partners in the past year was positively associated with concordant infection (odds ratio, 3.43; 95% CI, 1.06-11.06; P = .04). This analysis reveals the importance of several demographic factors (age and socioeconomic status) and behavioral factors (oral sex practices) in the development of dual and concordant HPV infection in women. Notably, other sexual behaviors, other sexually transmitted infections, sexual orientation, and number of lifetime sexual partners did not demonstrate any significant associations. Women with multiple oral sex partners and oral HPV infection have a high likelihood of having concurrent vaginal HPV infection.

Using the Cancer Risk Management Model to evaluate the health and economic impacts of cytology compared with human papillomavirus DNA testing for primary cervical cancer screening in Canada.

In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes.

Результаты генотипирования при ВПЧ-ассоциированном цервиците

Aim: to evaluate the quantitative and qualitative composition of cervical human papillomavirus (HPV) infection in chronic cervicitis (CC). Materials and methods. The study included 102 patients with cervical HPV infection, mean age 33,9±1,1 years. The 1st group (main) consisted of patients with CC (n=39), 2nd group (comparison) - the patients with cervical intraepithelial neoplasia - CIN (n=50), group 3 (comparison) - patients with cervical cancer (n=13). Complex diag-cer nostics included liquid cytology, colposcopic, and histological examination of cervical biopsies and endocervical samples, advanced screening for high risk HPV DNA (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 types) and low risk (6, 11 types) with viral load detection, screening for chlamydia and mycoplasmas DNA. Statistical analysis of data was performed using STATISTICA-6, functionality of MS Excel. Results. The prevalence of the same HPV type (56% and 64% respectively), two types (26 and 22%), three or more types (18 and 14%) in the 1st and 2nd group had no significant difference respectively. In the 1st group 45, 52 relative prevalence of HPV types was found in comparison with CIN, in which the predominance of 33 and 35 types of HPV (p 5 lg×105) was observed significantly more frequently (p 58, and 59 HPV types was shown in comparison with CIN, except for the viral load level.

MicroRNAs as new biomarkers for human papilloma virus related head and neck cancers.

Head and neck cancers are the sixth most common cancer in the world and the predominant type of which consist of squamous cell carcinomas (head and neck squamous cell carcinoma, HNSCC). Besides tobacco smoking and alcohol consumption, human papilloma virus (HPV) infection is the third leading cause of the occurrence of HNSCC. The presence of HPV is a distinct group of head and neck cancers exhibiting epidemiological, histopathological, clinical and prognostic differences opposed to the typical HNSCC. HPV positive HNSCC normally have a favorable prognosis compared with HPV negative HNSCC, so biomarkers suitable for the early detection of HPV positive HNSCC should be developed urgently to improve patient outcomes. HPV DNA screening is sensitive, but probably not useful because of the high prevalence of oral HPV and low risk of HNSCC. MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that act as post-transcriptional regulators of gene expression. Since miRNAs have a role in the cancer development and HPV status may affect the miRNAs expression pattern in HNSCC, the specific of miRNAs' expression in HPV positive HNSCC may expound the role of HPV in HNSCC and be new biomarkers for the early detection of HNSCC. More excitingly, saliva as proximal biofluid in the context of HNSCC contains a good deal of miRNAs. These miRNAs are stabile and may be suitable for noninvasive biomarkers of HNSCC.

Investigation of Transition Types of HPV DNA Test Results over Time in Korean Women.

Understanding the history of human papilloma virus (HPV) infection is important for interpretation of a positive HPV DNA screening test, future work-up and treatment. We investigated the transition of HPV DNA test results in Korean women, and analyzed the association of cytology result with transition type. We retrospectively reviewed annual HPV DNA test results for 5,274 subjects between January 2005 and December 2012. Each subject had a minimum of five annual tests over the eight-year period. Based on the pattern of results, the transition type for each subject was assigned to one of the following: negative, persistent, latent, transient, and unclassifiable. Associations of cytology results with the HPV DNA transition types, number of positive results, and the durations of positive results were also analyzed. The proportion of abnormal cytology findings decreased in the following order of transition patterns: persistent, latent, transient, and negative. Among transient patterns, a duration of three years or more significantly correlated with cytology results of non-high grade squamous intraepithelial lesion (HSIL; p<0.001). In the persistent group, duration of five years or more correlated with both non-HSIL and HSIL (p<0.001). Latent group showed no correlation with duration. Irrespective of patterns, having five or more positive results was significantly associated with HSIL (p<0.001). Our findings may contribute to better understanding of HPV infection, interpretation of HPV DNA screening results, and prediction of prognosis according to transition type.

Potential coverage of circulating HPV types by current and developing vaccines in a group of women in Bosnia and Herzegovina with abnormal Pap smears.

The objectives of this study were to identify human papillomavirus (HPV) genotypes in a group of Bosnian-Herzegovinian women with abnormal cytology and to assess their potential coverage by vaccines. HPVs were identified by multiplex real-time PCR test (HPV High Risk Typing Real-TM; Sacace Biotechnologies, Italy) of 105 women with an abnormal cervical Pap smear and positive high-risk (HR) HPV DNA screening test. The most common genotypes in the study were HPV-16 (32·6%, 48/147), HPV-31 (14·3%, 21/147), HPV-51 (9·5%, 14/147) and HPV-18 (7·5%, 11/147). The overall frequency of HR HPV-16 and/or HPV-18, covered by currently available vaccines [Gardasil® (Merck & Co., USA) and Cervarix®; (GlaxoSmithKline, UK)] was lower than the overall frequency of other HPVs detected in the study (40·1%, 59/174, P = 0·017). Group prevalence of HR HPVs targeted by a nine-valent vaccine in development (code-named V503) was higher than total frequency of other HPVs detected (68·0%, 100/147, P < 0·001). Development of cervical cytological abnormalities was independent of the presence of multiple infections (χ 2 = 0·598, P = 0·741). Compared to other HPVs, dependence of cervical diagnosis and HPV-16, -18 (P = 0·008) and HPV-16, -18, -31 (P = 0·008) infections were observed. Vaccines targeting HR HPV-16, -18 and -31 might be an important tool in the prevention of cervical disease in Bosnia and Herzegovina.