Human Papillomavirus Detection Rates Research Articles

Detection Rates of Human Papillomavirus Associated with Cervical Cancer in Women of Nizhny Novgorod

The purpose of the study was to assess detection rates of human papillomavirus in cervical cancer cases of Nizhny Novgorod. Materials and methods. We used the real-time polymerase chain reaction (PCR) to test samples of mucosa lining of the cervical canal and/or transformation zone taken from 630 women with cervical dysplasia of different degrees and 107 incident cases of cervical cancer that did not undergo treatment. The detection and differentiation of 14 genotypes of high-risk human papillomaviruses (HPV) was carried out using the AmpliSens® HPV HCR-genotype-FRT PRC kit. Results. The overall infection rate of women with oncogenic human papillomaviruses was 41.8%. Among the genotypes, HPV 16 (39.2%), 18 (15.5%), 33 (16.6%), and 56 (11.9%) predominated. A high prevalence of oncogenic HPV was detected in the women with cervical intraepithelial neoplasia (58.1%) and cervical cancer (90%). The spectrum of genotypes in women with neoplasia of various degrees differed. In women with CIN II and CIN III, vaccine-preventable HPV genotypes (HPV 16 and 18) playing the leading role in the development of cervical cancer were the most frequent. The same genotypes dominated in the women with invasive cervical cancer. One oncogenic HPV genotype was usually found in the infected women (69%). The high-risk HPV infection was often combined with Ureaplasma ssp (49.3%), Mycoplasma hominis (20.1%), Cytomegalovirus (21.1%), and Herpes simplex I/II (18.2%) infections. Combinations of high-risk HPV with Chlamydia trachomatis and Herpes 6 were found in 8.3% and 5% of the cases, respectively. Conclusions. Our findings proved a wide prevalence of high carcinogenic risk HPV 16 and 18 genotypes, thus indicating the expediency of using Cervarix and Gardasil vaccines registered in the Russian Federation and containing antigens to these types of virus for specific prevention of the HPV infection.

Human papillomavirus infection maybe not associated with primary lung cancer in the Fujian population of China.

BackgroundTo investigate whether human papillomavirus (HPV) infection is associated with primary lung cancer among the Fujian population.MethodsHPV infection was detected in 140 pairs of lung cancer tissues and matched paracancerous tissues by examining the 21 clinically relevant HPV types using a combination of viral highly conserved L1 region PCR amplification and specific probe reverse hybridization. Paired χ2 test was used to analyze differences in detection rates of HPV between lung cancer and paracancerous tissues. Differences in detection rates of HPV in lung cancer tissues were analyzed using χ2 test or the exact probability method. The rank sum test was used to analyze differences in the distributions of routine indices of blood and pulmonary function in lung cancer tissues between the HPV negative and positive groups.ResultsHPV infection was detected in 13 of the 140 tumor specimens and in 16 of the paired normal lung tissues. There was no significant correlation between HPV infection and lung cancer (P > 0.05). The diagnosed HPV infection rates did not differ significantly among lung cancer tissues with different stratification (P > 0.05). However, the platelet count, platelet pressure, residual gas volume, functional residual volume, and residual gas volume/lung total distribution may differ between HPV‐negative and HPV‐positive lung cancer tissues (0.000625 < P < 0.05).ConclusionsWe concluded that HPV infection may not be associated with the risk of primary lung cancer in the Fujian population. However, HPV infection may affect platelet and residual lung function in primary lung cancer patients.

Comparison and acceptability of HPV self-collected cervical cancer samples versus doctor-collected samples in Africa: a systematic review

Self-collected cervical cancer (CC) samples might be considered alternative strategy and provided an equivalent comparable result on HPV (Human Papillomavirus) detection and acceptability with clinician-collected sampled in Africa. A systematic review was performed using four electronic bibliographic databases (Pubmed, Cochrane, WHO Global health library and Popline) to compared HPV detection rate and acceptability of HPV self-vs clinician collected sampling in Africa. Specific search keywords were used. The study only focused on research articles that compared self-vs clinician-collected samples based on HPV testing and its associated data. Eight research articles and a total of 3476 women were included from six countries in Africa continent. The mean age of women was 40.6 years with range of 16-89 years. Aggregately the high risk (HR)-HPV detection rate was 36% (7.2% -84.8%) and 35% (6.8% - 87.8) of self-vs clinician-collected sampling, respectively. The mean differences and variation in detection rates between sampling methods was 2.6% (SD =1.7). There was significant HR-HPV detection rate correlation between two sampling methods with value of R=0.997. The weighted average of kappa agreement was 0.71(0.47 to 0.89) was moderate. Overall women concluded that self-collected sampling method was a preferred method (86.3%), easy to obtained (77.8%), and 76.7% increased cervical cancer screening uptake. The acceptability of self-collected CC sampled HPV testing could be an alternative sampling method and increased the uptake of screening services. Introducing standardized self-sampling techniques and diagnostic assay study in Africa is paramount.

The Contrast Research of Human Papillomavirus Infection Genotypes in Tissues of Cervical Squamous Cell Carcinoma and Cervical Adenocarcinoma

The large sample data of HPV genotypes on cervical squamous cell carcinoma (CSCC) and cervical adenocarcinoma (CAC) tissues are rarely reported in China. This study is aimed to investigate the clinical value of distribution of different kinds of genotypes of human papillomavirus (HPV) within regional (mainly in Jiangsu Province in China) patients of both CSCC and CAC. We collected tissue samples of from 1044 women with CSC (826 cases) and CAC (218 cases) in 29 hospitals of 6 Provinces in China from November 1978 to December 2017. HPV DNA was extracted and 23 genotypes of HPV were detected through the combination of gene-chip and polymerase chain reaction (PCR) technology to analyze distribution of HPV infection types among subjects of CSCC and CAC. Among 1044 cases of CSCC and CAC, 901 were found HPV positive making total HPV detection rate of 86.30% (901/1044). Total detection rate of CSCC was 91.53% (756/826) in which 16, 18, 58, 33, 52, 31 were the most common types where detection frequencies of 16 and 18 types were 56.84% (544/957) and 9.93% (95/957), respectively. Total detection rate of CAC was 66.51% (145/218) in which 16, 18, 31, 33, 52, 58 were the most common types where detection frequencies of 16 and 18 types were 35.29% (84/238) and 32.35% (77/238), respectively. The HPV detection rates were different in female CSCC and CAC tissues of region studied. The 16, 18, 31, 33, 52 and 58 types are the most common genotypes found in two sorts of cervical carcinoma tissues. The detection rate of 16 types was higher than 18 types in CSCC and were very close in CAC tissues. Conducting HPV genotypes detection of CSCC and CAC will help doctors evaluating onset risk of cervical carcinoma and tracking HPV infected patients with high cancerogenic risk. The early detection will play important role in prevention and treatment of female CSCC and CAC in our nation.

The Prevalence, Anatomic Distribution and Significance of HPV Genotypes in Head and Neck Squamous Papillomas as Detected by Real-Time PCR and Sanger Sequencing

Squamous papillomas (SPs) of the head and neck are generally regarded as a human papillomavirus (HPV)-driven process, but reported rates of HPV detection vary dramatically. Moreover, they are generally considered a benign condition, but the detection of high risk HPV types is commonly reported. This latter finding is particularly disturbing to clinicians and their patients given the alarming rise of HPV-associated head and neck cancer. The capriciousness of HPV detection reflects in large part differences in methodologies. The purpose of this study was to review an institutional experience using a state of the art detection method to determine the presence, type and anatomic distribution of HPV in head and neck SPs. The surgical pathology files of the Mount Sinai Hospital were reviewed for all SPs that had undergone HPV testing between 2012 and 2018. HPV screening was performed on tissue blocks with real-time PCR using primers designed to target the L1 region of low and high-risk HPV types. Genotyping was performed on HPV positive cases. HPV detection was repeated for cases that were originally reported to be positive for high risk HPV. 134 cases had undergone HPV analysis. Of the 131 with sufficient cellular material, 2 were excluded because the HPV testing yielded inconclusive results. The remaining 129 cases were the basis of this study. Thirty-eight cases (29%) were HPV positive and 91 (71%) were negative. The most common genotype was HPV 6 (n = 27, 71%), followed by HPV 11 (n = 10, 26%). One case (1%) was HPV positive but the genotype could not be determined. Of the HPV negative cases, 3 were originally reported as HPV 16 positive but found to be HPV negative on re-review and repeat testing. SPs arising in the larynx were more likely to harbor HPV than those arising in the oral cavity and oropharynx (64% vs. 10%, p < 0.00001). Similarly, recurrent respiratory papillomatosis (RRP) were much more likely to be HPV positive than solitary SPs (71% vs. 10%, p < 0.00001). Almost a third of head and neck SPs harbor HPV, but incidence is highly dependent on anatomic site. Those arising in the larynx are more prone to be HPV-driven than those arising in the oral cavity and oropharynx, particularly when occurring in the setting of RRP. High risk HPV could not be confirmed in any of the cases. Routine HPV testing as a strategy to unmask potentially malignant lesions harboring high risk HPV is not likely to be useful.

HPV genoprevalence and HPV knowledge in young women in Mongolia, five years following a pilot 4vHPV vaccination campaign

BackgroundIn a 2012 pilot, 9111 Mongolian girls aged 11–17 years received three doses of the quadrivalent (4vHPV) vaccine, Gardasil®. This is the first study to measure early vaccine effectiveness and assess knowledge and attitudes of young women in Mongolia in relation to the human papillomavirus (HPV), the vaccine and cervical cancer. MethodsA cohort of women vaccinated in 2012 (n = 726) and an unvaccinated cohort (n = 790) provided self-administered vaginal swabs for detection of high-risk HPV genotypes 16, 18/45, 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, 68 five years following vaccination. Participant knowledge and attitudes were assessed through a questionnaire. ResultsA total of 1882 questionnaires and 1516 self-administered vaginal swabs were analyzed. The prevalence of any HRHPV was 39.5% among both cohorts. The prevalence of vaccine-targeted HPV types was significantly lower in the vaccinated cohort than unvaccinated: 4.8% and 17.2% respectively. The 4vHPV was shown to be protective against HRHPV 16, 18/45 with 75% vaccine effectiveness. Participant knowledge was low. ConclusionsThis study demonstrates that the 4vHPV is associated with reduced vaccine-targeted HPV detection rates in young Mongolian women. The questionnaire results highlight a need for awareness-raising initiatives in Mongolia on HPV, the vaccine and cervical cancer.

HPV testing compared with routine cytology in cervical screening: long-term follow-up of ARTISTIC RCT.

The National Screening Committee (NSC) based its recommendation that human papillomavirus (HPV) testing should replace cytology in primary cervical screening largely on the 2009 follow-up results of the ARTISTIC trial (A Randomised Trial In Screening To Improve Cytology). The NSC must now decide on screening intervals and triage policy. Options include extending the screening interval up to 10 years for human papillomavirus-negative (HPV-) women, delaying recall for human papillomavirus-positive (HPV+) women with normal cytology (as their infections are usually transient), and basing triage on full HPV typing. In ARTISTIC, 24,510 women were recruited who were attending routine cervical cytology in Greater Manchester in 2001-3. The women were randomly allocated between revealing and concealing their HPV test results and were recalled every 3 years. After 2009, the women returned to routine cytological screening with recall every 3 years for those aged < 50 years, and every 5 years for those aged 50-64 years. We have followed the cohort to 2015 through national cancer registration for CIN3 (cervical intraepithelial neoplasia grade 3) and cancer, and through linkage to the cervical screening call-recall system to obtain lifetime cytology records. The analysis comprised 24,496 women at round 1 and 13,591 women at round 2 (which was 30-48 months later). Follow-up via local histology laboratories and national cancer registration identified 505 cases of cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+) (including 22 invasive cervical cancers). The cumulative CIN3+ risk 10 years after a negative HPV test [0.31%, 95% confidence interval (CI) 0.18% to 0.49%, in the revealed arm] was similar to that 3 years after negative cytology (0.30%, 95% CI 0.23% to 0.41%, in the concealed arm) and fell sharply with age, from 1.1% (95% CI 0.7% to 1.8%) in those women aged < 25 years to 0.08% (95% CI 0.03% to 0.20%) in those women aged > 50 years. The 10-year cumulative CIN3+ risk following a new HPV infection at round 2 was 3.4% (95% CI 2.1% to 5.4%). The highest risks were associated with type-specific persistent infections that, overall, resulted in a 10-year cumulative CIN3+ risk of 20.4% (95% CI 15.6% to 26.4%). We found a similar level of protection 10 years after a negative HPV test and 3 years after negative cytology. These data support a considerably longer screening interval after a negative HPV test than after a negative cytology test. About three-quarters of women with HPV infection and normal cytology clear their infections within about 3 years. Their risk of CIN3+ within this time frame is low (1.5%), suggesting that the current policy of annual repeat testing and referral after 2 years may be unnecessarily cautious. Approximately 40% of women who remained HPV+ had cleared their initial infection and acquired a new HPV type. The cumulative CIN3+ risks in women with type-specific persistent infections are about six times higher than in women with new infections. Triage strategies based on HPV persistence would, therefore, reduce unnecessary referral of women with new (and largely transient) infections. HPV assays that identify HPV types 31, 33, 45, 52 and 58 in addition to 16 and 18 could be useful in triage as well as in primary HPV testing. Similar results in recent routine HPV screening suggest that our results are generalisable despite changes in cytology and HPV assay methods. We are continuing to follow the ARTISTIC cohort into the new era of primary HPV screening. Future work will focus on the implications of more sensitive HPV testing for primary HPV screening policy and triage of HPV-positive women. Our results suggest that a more sensitive test is needed to detect occult CIN3 at high risk of progression to cancer, but this would substantially increase the overall HPV detection rate. Tests such as DNA (deoxyribonucleic acid) methylation for distinguishing HPV infection from neoplasia will be evaluated on stored samples and on further samples now being collected from women in the cohort who are still being screened. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 28. See the NIHR Journals Library website for further project information.

Prevalence and distribution of human papillomavirus genotypes among women with high-grade squamous intraepithelial lesion and invasive cervical cancer in Ganzhou, China.

Human papillomavirus (HPV) infection can lead to the development of cervical cancer. This study assessed the genotype distribution of HPV of high-grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer (ICC) in Ganzhou population. A total of 935 females who got HPV testing from January 2016 to July 2018 in the maternal and child health hospital of Ganzhou were enrolled in the study, including 806 HSIL and 129 ICC. HPV detection and genotyping were tested by HPV Geno-Array test kit. The overall HPV-positive rate was 74.0% in Ganzhou. Among the HSIL and ICC patients, the positive rates of HPV detection were 75.6% and 64.3%. Among the HSIL individuals, the most prevalent hr-HPV genotype was HPV 16. And the 4 common subtypes in decreasing order were HPV 52, 58, 33, and 18. Of the ICC patients, the most frequently hr-HPV subtype was HPV 16 followed by 18, 52, 58, and 59. Among the squamous cell carcinoma (SCC) patients, for hr-HPV genotypes, HPV 16, 18, 52, 58, and 59 were five most common subtypes. In patients with adenocarcinoma (ADC), the most common hr-HPV genotype was HPV 18, followed by HPV 16, 52, 56, 68, 73. And, we found U-shaped and S-shaped curves in the HPV distribution of different age groups. The prevalence and distribution of HPV genotypes in Ganzhou differed from other regions of China and Western countries. These results can serve as valuable reference for HPV vaccination programs for Ganzhou women.

Detection of Incident Anal High-Risk Human Papillomavirus DNA in Men Who Have Sex With Men: Incidence or Reactivation?

We aimed to assess whether sexual exposure may explain all incident anal human papillomavirus (HPV) detections among men who have sex with men (MSM). A longitudinal study among MSM was conducted between 2010 and 2013 with visits every 6 months and up to 24 months of follow-up. Risk-factor questionnaires, blood samples, and anal and penile self-swabs were collected at each visit. Self-swabs were used for detection and genotyping of HPV by the broad spectrum L1 based SPF10 PCR DNA/enzyme immunoassay LiPA25 system. Serum samples were tested for high-risk HPV (hrHPV) antibodies. Incident anal HPV detection rates among sexually non-, low, and highly exposed MSM were compared. Factors associated with incident anal hrHPV detection were assessed using multivariable Cox regression. Seven hundred fourteen men (median age, 40 years; 39% human immunodeficiency virus [HIV] infected) were included in the analysis. Incident anal detections of all hrHPV types were observed among both sexually nonexposed and exposed MSM. In multivariable analyses, being highly sexually exposed, being HIV infected, and having a penile HPV infection were positively associated with incident anal HPV detection; those reporting more sex partners had a nonsignificantly increased risk of HPV detection. Incident anal hrHPV detection is common among recently nonexposed MSM, suggesting that a reactivated latent HPV infection instead of an incident infection may underlie incident HPV detection.

Can Human Papillomavirus DNA Self-sampling be an Acceptable and Reliable Option for Cervical Cancer Screening in Female Sex Workers?

The causal relation between human papillomavirus (HPV) and cervical cancer has enabled HPV self-sampling to be envisaged as a possible screening method. The aim of this study is to explore the acceptability and reliability of HPV DNA self-sampling as an alternative option for cervical screening among female sex workers. Sixty-eight participants carried out self-sampling for HPV testing, gave a clinician-obtained sample for HPV testing, and a Papanicolaou test. After the samplings, the participants were questioned on the acceptability of the tests. Most participants (65.6%) preferred to adopt HPV DNA self-sampling in the future; in particular, those without previous experience of Papanicolaou tests marginally significantly preferred self-sampling (86.7%, P = .055). The overall crude agreement in HPV detection rates between clinician and HPV DNA self-sampling was 85.3% (58/68), with a κ of 0.69 (95% confidence interval, 0.51-0.87). The sensitivity and specificity of self-collected samples were 66.7% and 66.1%, respectively, and the positive and negative predicted values were 24.0% and 92.5%, respectively. The prevalence of HPV was slightly higher in self-collected samples (39.7%, 27/68) than in clinician-collected samples (36.8%, 25/68). The participants expressed positive attitudes toward self-sampling but were less confident in their skills of self-sampling compared with clinicians (70.6% versus 91.2%). The findings showed that self-sampling could be incorporated into current cervical cancer screening approaches. Self-sampling could potentially increase compliance to cervical cancer screening and thus reduce the morbidity and mortality from cervical cancer. Further research and education on self-sampling will be required for women of diverse backgrounds.

Co-infection Of Ureaplasma urealyticum And Human Papilloma Virus In Asymptomatic Sexually Active Individuals.

This study aimed to determine the role of asymptomatic bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis (Ct), Mycoplasma genitalium (Mg), Mycoplasma hominis (Mh), and Ureaplasma urealyticum (Uu) in human papillomavirus (HPV) infection.In total, 264 asymptomatic outpatients aged between 21 and 80 years were prospectively enrolled in this study during routine gynecological screening tests. Specimens collected with a Cervex Brush were routinely analyzed with the Hybrid Capture 2 assay for HPV. Simultaneously, a specimen obtained with an endocervical swab was used to detect Ct and Mg with a monoplex real-time polymerase chain reaction (PCR) and to confirm Mh and Uu with a Mycoplasma IST 2 kit.The detection rates (%) of HPV, Ct, Mg, Mh, and Uu were 82/264 (31.1), 6/264 (2.3), 5/264 (1.9), 16/264 (6.1), and 95/264 (36.0), respectively. Of 95 Uu, 32 (33.7%) showed high density colonization (HDC, ≥104 color-changing units/mL). HDC-Uu was significantly associated with HPV infection (p=0.014, chi-square test). Mg infection and Mh infection were not associated with HPV infection (p=0.981 and p=0.931, chi-square test). Age was not associated with HPV infection or bacterial infection.Our data suggested that asymptomatic HDC-Uu was closely associated with HPV infection. Therefore, simultaneous evaluation for Uu and HPV should be performed during gynecological screening, even in asymptomatic individuals.

Nonuniform Distribution of High-risk Human Papillomavirus in Squamous Cell Carcinomas of the Oropharynx

The oral cavity and oropharynx have historically been viewed as a single anatomic compartment of the head and neck. The practice of combining the oral cavity and oropharynx has recently been revised, largely owing to the observation that human papillomavirus (HPV)-related carcinogenesis has a strong predilection for the oropharynx but not the oral cavity. The purpose of this study was to determine whether HPV is evenly distributed across squamous cell carcinomas of the oropharynx including those sites that do not harbor tonsillar tissues such as the soft palate. A search of the medical records of the Johns Hopkins Hospital identified 32 primary squamous cell carcinomas of the soft palate (n=31) and posterior pharyngeal wall (n=1). All were evaluated with p16 immunohistochemistry and high-risk HPV in situ hybridization (ISH) (29 by RNA ISH and 3 by DNA ISH). For comparison, we also reviewed the medical records to obtain the HPV status of patients who had undergone HPV testing of primary tonsillar carcinomas over the same time interval as part of their clinical care. High-risk HPV as detected by ISH was present in just 1 (3.1%) of the 32 oropharyngeal squamous cell carcinomas, including 1 of 2 p16-positive carcinomas. The difference in HPV detection rates between tonsillar and nontonsillar sites was significant (1/32, 3.1% vs. 917/997, 92%; P<0.0001). HPV is not frequently detected in squamous cell carcinomas arising from nontonsillar regions of the oropharynx. Indeed, squamous cell carcinomas of the soft palate more closely resemble those arising in the oral cavity than those arising in areas of the oropharynx harboring tonsillar tissue. This finding not only further sharpens our understanding of site-specific targeting by HPV, but may have practical implications regarding HPV testing and even the way the oral vault is oncologically compartmentalized to partition HPV-positive from HPV-negative cancers.

Prevalence of anal, oral, penile and urethral Human Papillomavirus in HIV infected and HIV uninfected men who have sex with men.

Aims of the study were to evaluate Human Papillomavirus (HPV) and type-specific prevalence in four anatomical sites in HIV infected men who have sex with men (MSM) compared with HIV uninfected MSM. Participants were recruited among the attendees of Infectious Diseases Clinics in Central Italy. A trained medical practitioner collected by interview sociodemographic data and information on medical history, sexual behavior, and drug use. Swabs from anal canal, oral cavity, urethral mucosa, and coronal sulcus were tested for HPV DNA and genotyping. Ninety MSM were enrolled, 45 subjects within each group. Overall, 48.9% MSM were HPV positive and prevalence was higher in HIV infected men (60.0% vs 37.8%, P = 0.035). HPV at multiple anatomic sites occurred in 59.1% MSM, with 34.1% and 22.7% at two and three sites, respectively. Prevalence of anal, coronal sulcus, oral, and urethral HPV was 96.3%, 37%, 21.6%, and 18.5% in HIV infected MSM, and 70.6%, 70.6%, 29.4%, and 23.5% among HIV uninfected. A similar proportion of HIV infected and uninfected MSM (59.2% and 58.8%) carried at least one high-risk genotype. Prevalence of types covered by nonavalent vaccine was 77.8% in HIV infected compared with 82.3% in HIV uninfected MSM. HPV 58 and 16 were mostly detected in HIV positive (43.7% and 31.2%) and negative MSM (50.0% and 40.0%). HPV detection rate underlined the high vulnerability of MSM to acquire multisite infections, characterized by various genotype combinations. Since nonavalent vaccine could have prevented 80% of HPV infections, study findings support the implementation of vaccination programs among MSM.

Comparison of human papillomavirus (HPV) detection in urine and cervical swab samples using the HPV GenoArray Diagnostic assay.

Human papillomavirus (HPV) is the leading cause of cervical cancer. Urine-based HPV testing offers a simple and non-invasive method because of its increasing acceptance. A total of 164 pairs of cervical swab and urine samples from Thai women who underwent cervical cancer screening were used for HPV testing with HPV GenoArray Diagnostic Kits. The overall concordance percentage for HPV detection in the cervical swab and urine samples was 65.2%. The HPV genotypes most commonly detected were HPV16 and HPV18. An analysis of the urine samples and a second analysis of the cervical swab samples showed that the differences in the overall HPV detection rate between women with normal and abnormal cytology were not significant (p > 0.05). Urine samples processed with the GenoArray assay is an alternative for women who decline to undergo Pap smear even though it is not ideal as the first-line screening option.

Using p16 immunohistochemistry to classify morphologic cervical intraepithelial neoplasia 2: correlation of ambiguous staining patterns with HPV subtypes and clinical outcome

p16INK4a immunohistochemistry (IHC) is widely used to facilitate the diagnosis of human papillomavirus (HPV)-associated cervical precancerous lesions. Although most p16 results are distinctly positive or negative, certain ones are ambiguous: they meet some but not all requirements for the "block-positive" pattern. It is unclear whether ambiguous p16 immunoreactivity indicates oncogenic HPV infection or risk of progression. Herein, we compared HPV genotypes and subsequent high-grade squamous intraepithelial lesion (HSIL) outcomes among 220 cervical biopsies with a differential diagnosis of cervical intraepithelial neoplasia 2 based on hematoxylin and eosin morphology and varying degrees of p16 immunoreactivity. p16 results were classified as block positive (n=40, 18%), negative (n=130, 59%), or ambiguous (n=50, 23%), a category we further grouped into 3 patterns: strong/basal (n=18), strong/focal (n=15), and weak/diffuse (n=17). Seventy percent of ambiguous p16 lesions were negative for the most common low- and high-risk HPV types; the remaining 30% were positive for HPV 16, 18, 45, 58, 59, or 66. Three patterns revealed comparably low HPV detection rates (28%, 27%, and 35%). During 12-month surveillance, HSILs were detected in 35% of the p16 block-positive group, 1.5% of negative group, and 16% of the ambiguous group. The accuracy of ambiguous p16 immunoreactivity in predicting oncogenic HPV and HSIL outcome is significantly lower than that of the block-positive pattern but greater than negative staining. Specific guidelines for this intermediate category should prevent diagnostic errors and help implement p16 IHC in general practice.

Plasma HPV DNA is detectable in oral leukoplakia patients

BackgroundOral leukoplakia is considered a potentially malignant lesion for the development of squamous cell carcinoma, and various risk factors may be related to its development and malignant transformation, including the human papillomavirus (HPV). The aim of this case-control study was to detect the presence of HPV in fresh tissue, plasma and saliva samples obtained from patients with and without oral leukoplakia, and verify the correlation of the presence of DNA of HPV between different sources of materials. MethodsIn this study, 32 patients with oral leukoplakia and 24 patients selected in a case-control manner were included. DNA extraction from the samples was performed, and afterwards it was amplified by nested polymerase chain reaction (nPCR) for the detection of HPV (nPCR: MY09-MY11/GP05+-GP06+). ResultsThe DNA of HPV was found in 68.75% of the fresh tissue samples; in 50% of plasma, and in 62.5% of saliva samples in the group of patients with leukoplakia; in comparison with 45.8%, 54%, and 45.8%, in the fresh tissue, plasma and saliva samples, respectively, in the control group. ConclusionBased on the present study, there was no difference in the rate of HPV detection in patients with or without oral leukoplakia. However all sources tested in this study were considered suitable for HPV detection, especially plasma samples, which showed be an important non-invasive source of HPV detection in leukoplakia patients.

Transcriptionally Active High-Risk Human Papillomavirus is Not a Common Etiologic Agent in the Malignant Transformation of Inverted Schneiderian Papillomas.

The role of human papillomavirus (HPV) as an etiologic and transformational agent in inverted Schneiderian papilloma (ISP) is unclear. Indeed, reported detection rates of HPV in ISPs range from 0 to 100%. The true incidence has been confounded by a tendency to conflate high- and low-risk HPV types and by the inability to discern biologically relevant from irrelevant HPV infections. The recent development of RNA in situ hybridization for high-risk HPV E6/E7 mRNA now allows the direct visualization of transcriptionally active high-risk HPV in ISP, providing an opportunity to more definitively assess its role in the development and progression of ISPs. We performed p16 immunohistochemistry and high-risk HPV RNA in situ hybridization on 30 benign ISPs, 7 ISPs with dysplasia, 16 ISPs with carcinomatous transformation, and 7 non-keratinizing squamous cell carcinomas (SCCs) with inverted growth that were unassociated with ISP. Transcriptionally active HPV was not detected in any of the 52 ISPs including those that had undergone carcinomatous transformation, but it was detected in two of seven (29%) non-keratinizing SCCs that showed inverted growth. There was a strong correlation between high-risk HPV RNA in situ hybridization and p16 immunohistochemistry (97%; p < 0.01). These results indicate that transcriptionally active high-risk HPV does not play a common role in either the development of ISP or in its transformation into carcinoma.

Analysis of HPV subtype infection in 4 037 healthy women in Haikou area

Objective To investigate the infection of 23 kinds of human papillomavirus (HPV) subtypes in female cervical epithelium samples and to analyze their relationships with age and results of cytologic test in Haikou area. Methods A total of 4 037 local healthy women were enrolled in this study from July 2013 to August 2016, 1 967 of whom received cervical cytology test. Cervical cell samples collected from those women were detected for HPV typing by using PCR-reverse dot blot hybridization. Results (1) The total positive rate of HPV in 4 037 samples was 22.15% (894 cases), and the detection rates of carcinogenic, possibly carcinogenic and non-carcinogenic HPV were 16.13%, 3.99% and 5.55% (651, 161 and 224 cases), respectively. The positive rates of 6 genotypes were high, which were HPV52, 53, 81, 51, 16 and 58 in turn. (2) The detection rates of carcinogenic, possibly carcinogenic HPV and some of the genotypes (HPV18, 52, 53, 66) increased with age (all P<0.05). (3) Multiple infection in HPV-positive women accounted for 24.38% (218/894), in which the infection rates of carcinogenic types declined with age and the numbers of HPV genotypes in carcinogenic infections were negatively correlated with age (both P<0.05). (4) Only 2.49% (49/1 967) of the samples were positive for cervical cytologic test, classified into the ≥ASC-US (atypical squamous cells of undetermined significance) group. The detection rates of eight kinds of carcinogenic and two kinds of possibly carcinogenic HPV in ≥ASC-US group were significantly higher than those in the negative (no intraepithelial lesion or malignant lesion, NILM) group (all P<0.05). Conclusion This study indicates that Haikou women have higher rates of HPV infection, especially the elderly group. HPV subtype infections present some regional characteristics and are mainly single type infection. Cervical cancer screening should be combined with tests for HPV and cytology analysis to improve its effectiveness. Key words: Human papillomavirus; PCR-reverse dot blot hybridization; Genotyping; Multiple infection; Liquid based cytology

Detection of Human Papillomavirus Infection in Patients with Vaginal Intraepithelial Neoplasia.

IntroductionVaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions.Patients and Methods67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System).ResultsAll 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL (VAIN) was 53 years and in patients with HSIL (VAIN) 53.5 years. 12 women (18%) had an immunosuppression. HPV positivity was confirmed in 37 patients (55%). Except for a single patient, who had a triple infection with HPV types 6/11, 16 and 68, only infections with one single HPV genotype were detected. An infection with the HPV genotypes 31, 39, 45, 51, 58, 59, 66, 42, 43 and 44 couldn’t be found in any of the patients. In 28 patients with diagnosed VAIN, an infection with HPV 16 could be shown, 24 (86%) of them were diagnosed with a HSIL (VAIN). 16 (24%) women presented condylomata and 13 of them (81%) had a positive HPV status. However, only 47% of the women without condylomata presented a positive HPV status, resulting in a significant correlation (p = 0.0164) between condylomata and HPV infection. In 28 of all 67 patients (42%), recurrence of the neoplasia occurred.ConclusionHPV 16 is the main virus-type to be associated with the development of a VAIN. Also, HPV 16 infection, VIN or condylomata acuminata in the past medical history seemed to be significant factors for early relapse.

Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol's iodine (VIA/VILI) in Libreville, Gabon.

BackgroundThe human papillomavirus (HPV) is the causative agent of cervical cancer, which is the leading cancer-related cause of death for women in Sub-Saharan Africa. In 2013, the Gabonese Ministry of Health and the Sylvia Bongo Ondimba Foundation implemented cervical cancer screening programs based on the detection of cancerous lesions by visual inspection with acetic acid and/or Lugol’s iodine (VIA/VILI). This pilot study was set up to determine the HPV profile and analyze the nucleotide sequence variation of HPV16 circulating in patients with cervical abnormalities detected by VIA/VILI testing.MethodsThe cervical abnormalities observed upon VIA/VILI were confirmed by liquid-based cytology for all tested women. Nested PCR using the MY09/11 and GP5+/6+ primer sets was used to detect HPVs present in the extracted DNA. HPV genotypes were determined after sequencing of amplicons based on a high-throughput sequencing approach. For isolates of the HPV16 genotype, the E6 gene and the long control region (LCR) were directly sequenced using Sanger method.ResultsThe study included 87 women who showed a positive VIA/VILI result. Cervical abnormalities were found in 40.23 % of women and 40 % were classified as high-grade lesions. The HPV detection rate was 82.9 % among women with abnormal cytology. Among all the identified high-risk HPV genotypes, HPV16, 18 and 33 were the most frequent. Multiple HPV infections were observed in 42.31 % of HPV-infected women. Analysis of the HPV16 sequence variation in the E6 gene and in the LCR showed that 85.3 and 14.7 % belonged to the African and European lineages, respectively. Among the African branch variants, Af2 was the most frequently identified in this study.ConclusionThis study offers the first report of the HPV detection rate and molecular epidemiology among Gabonese women with a positive result in a VIA/VILI screening test. Moreover, data on the HPV16 sequence variation confirm the predominance of African variants in high-grade lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-016-0098-1) contains supplementary material, which is available to authorized users.