Global cervical cancer incidence and mortality rank fourth in women with malignant tumors, which have been reduced by population-based cervical cancer screening. The previously used Papanicolaou cytological testing of cervical smears was replaced by the Bethesda classification, which facilitated the early detection of the pre-cancerous lesions, used together with other methods such as colposcopy, testing of high-risk genotypes of human papillomavirus (hrHPV) and molecular techniques. The recently introduced terminology as ASC (atypical squamous cells), ASC-US (ASC, undetermined significance), ASC-H (ASC, cannot exclude HSIL), as well LSIL and HSIL (low- and high-grade squamous intraepithelial lesions) is widely used in Hungary, which guides the treatments of the patients by the clinicians. The detection of HPV is incorporated into the management of the patients as well. It is, however, highly important to update the domestic cervical cancer screening, especially with the introduction of the first-line, primary HPV screening in Hungary, in agreement with the opinions of other groups.

The Aptima human papillomavirus (HPV) test (APTIMA) detects E6-E7 mRNA in abnormal cells in the uterine cervix. To investigate the accuracy of APTIMA for cervical cancer screening in Japan, 423 subjects, mostly referrals with abnormal cytology or being followed up for cervical intraepithelial neoplasia (CIN)1, were screened using two HPV tests, hybrid capture 2 (HC2) and APTIMA, and by the Pap test. Colposcopy was conducted in all subjects with a positive result in either test type. HPV genotyping was performed by Genosearch-31. A result of atypical squamous cells-undetermined significance (ASC-US) or worse on the HC2 test (ASC-US-HC2), and low-grade squamous intraepithelial lesion (LSIL) or worse (LSIL+) on the Pap test, was regarded as positive. APTIMA (97.5%) was more sensitive than LSIL+ (85.1%) for detecting CIN2 or worse (CIN2+) (McNemar test; p = .0003), and more sensitive (98.6%) than ASC-US-HC2 (92.7%) for detecting CIN3+. APTIMA and HC2 had similar sensitivities. HPV genotyping revealed that CIN2/3 with high-risk HPV (HR-HPV) was overlooked in five cases by ASC-US-HC2, and in four cases by HC2, while no such lesions were missed by APTIMA. Thus, APTIMA might be superior to HC2 for primary HPV screening in Japan. One cancer case positive for HPV67 (potentially high risk, [pHR]) was overlooked by Pap test and both HPV tests, suggesting a need for a new HPV test able to detect pHR-HPV types.

Objective: To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions. Methods: A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval (CI) of high-risk HPV and HPV16/18 tests were calculated. Results: The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95%CI: 75.8%-96.8%) and 78.0% (95%CI: 74.5%-81.2%) as well as 56.3% (95%CI: 39.3%-71.8%) and 95.7% (95%CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95%CI: 88.1%-98.1%) and 87.6% (95%CI: 86.9%-88.2%) as well as 65.9% (95%CI: 55.1%-75.2%) and 97.8% (95%CI: 97.5%-98.1%), respectively. Conclusions: The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.

The standard screening test for detecting cervical lesions and cancers is a Papanicolaou (Pap) smear. While squamous cell abnormalities remain the most common positive Pap test result, cytologic findings of glandular cell abnormalities have become more frequent in recent decades. The 2014 Bethesda System for reporting cervical cytology includes the classification "atypical glandular cells" (AGC). AGC have morphological abnormalities that fall outside the range of reactive changes, but are insufficient for a diagnosis of invasive adenocarcinoma. In several histologic follow-up studies, most AGC cases were found to represent a benign condition. In the current study, we evaluate the significance of AGC cytology findings by analyzing the histologic follow-up results of a large number of patients with AGC. Most patients with AGC in this study were found to have a significant lesion on follow-up (63.9%), with negative histologic results in only 36.1% of patients. Among patients with significant lesions, the most common result was low-grade squamous intraepithelial lesion (26.6%), followed by high-grade squamous intraepithelial lesion (23.2%). This provides further evidence to support the Chilean Clinical Guidelines for Cervical Cancer, which recommends diagnostic follow-up studies in all women with AGC to minimize the chance of undetected serious cervical disease.

The 2014 Bethesda System diagnostic criteria for atypical glandular cells (AGC) aid in the classification of atypical cells in cervical cytology. Anyway, AGC diagnosis remains challenging, due to low frequencies of this finding (approximately 0.5%-1% of Pap test results), abundance of AGC mimics, and significant interobserver variability. We developed an algorithm based on nuclear areas parameter that can help to differentiate AGC from Normal and Reactive glandular cells. Nuclear areas and perimeters were measured on 16 Pap smears with AGC and 18 with Reactive glandular cells of women aged between 30 and 77. Glandular cells from nonpathological Pap smears were used as controls. For each case, the means, medians, standard deviations, and the minimum and maximum values of both nuclear areas and perimeters of the cells of interest were calculated. The nuclear area analysis showed a 100% specificity in discriminating Normal from Altered cells (either Reactive or AGC), whereas the nuclear perimeter analysis showed a lower specificity (87.5%). Both nuclear area and perimeter variability analysis resulted in high specificity values in distinguishing Reactive cells from AGC. Therefore, a stepwise two-step algorithm using nuclear areas to discriminate Normal from Altered cells, and nuclear area variability to distinguish Reactive from AGC, allowed us to reliably classify the cells into these three categories. The morphometric analysis of nuclear area is a valuable and reliable aid in AGC diagnosis and standardization, easily integrable into common automatic algorithms.

Human papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.

This study compares Xpert® HPV and Hybrid Capture® 2 High-Risk HPV DNA Test™ (hc2) for the detection of high-risk HPV infection in cervical smears. Papanicolaou smears with atypical squamous cells of undetermined significance (ASC-US) constituted the study specimens. Of the 168 ASC-US samples, 134 (79.8%) were from Saudi patients. The hc2 test was positive in 33 (19.6%) of the total patients, 20% among Saudi patients, and 17.6% among non-Saudi patients. Xpert® HPV produced positive results in 30 (17.8%) of the samples. The overall concordance rate between the two tests was 98.2%, and the positive concordance rate was 91%. There were three samples tested positive by hc2 that tested negative by Xpert® HPV. HPV 16, HPV 18/45 and HPV other types were the most common types. Both tests have a reasonable positive concordance rate, although hc2 detected more cases than Xpert® HPV. Xpert® HPV provides a viable alternative to the hc2 test with similar detection results for samples with ASC-US.

Homosexual men infected with human immunodeficiency virus (HIV) are at a greater risk of developing anal cancer. Men who are infected with HIV and visited the outpatient clinics in Taoyuan General Hospital were enrolled to this study. During March to December 2011, thin preparation anal Pap smear and human papillomavirus (HPV) genotyping were performed in 230 subjects, of which 69 subjects underwent anoscopic biopsy. Their mean age was 32.9 ± 8.1 years, and 181 (78.6%) men were homosexual. The proportion and 95% confidence interval (CI) of subjects with anal dysplasia in cytology was 23.0% (17.56-28.44), including 13.4% (9.26-18.14) with atypical squamous cells of undetermined significance, 7.0% (3.70-10.30) with low-grade squamous intraepithelial lesions, and 2.6% (0.54-4.66) with high-grade squamous intraepithelial lesions. For participants having atypical squamous cells of undetermined significance or higher grades, multivariate logistic regression models yielded adjusted odds ratios (95% CI) of 12.61 (1.63-97.56) for homosexuality, 1.62 (1.31-2.00) for number of oncogenic HPV types, and 1.01 (1.00-1.02) for number of lifetime sexual partners. For detection of histological grade II or III anal intraepithelial neoplasm in anoscopic biopsies, the sensitivity of sequential tests for oncogenic HPV and cytology with atypical squamous cells of undetermined significance or higher grades was 100%. The positive likelihood ratio was 3.09 (P = 0.05). It is important to consider anal cancer precursors among homosexual men who are infected with HIV. Anal cytology and oncogenic HPV genotyping testing are effective screening methods.

Between the years 2008-2011 reverse hibridisation (INNO-LiPA HPV Genotyping Extra test) and genotyping 1a Roche (the kit: Linear array HPV genotyping test) were used for detection of Human Papilloma Virus (HPV) in the cervix secretions of 182 female patients aged 16-63 years, predominantly of urban origin. 99 patients (54.4%) were identified as being infected with various types of HPV, prevalent in urban (53 single infections and 46 multiple infections). HPV infection was not detected in 83 (45.6%) patients. Only 7 females from rural areas were tested (5 females had single or multiple HPV infections). 32 types of HPV were identificated: 15 HPV types with high risk (51, 82, 56, 18, 39, 45, 59, 68, 16, 31, 33, 35, 52, 58, 73), 14 types with low risk (42, 61, 62, 72, 81, 83, 84, CP6108, 70, 6, 11, 55, 74, 54), and 3 types with possible high risk (26, 53, 66). The type of HPV could not be identified in other two cases. The most frecvent types of HPV with high risk isolated were: the type 16. The types 51 and 58 of HPV with high risk and the type 84 with low risk are detected in single infections in urban and in rural. HPV clades involved in single infections are: 1 (1 case), 3 (5 cases), 5 (4 cases), 6 (5 cases), 7 (5 cases), 9 (21 cases), 10 (7 cases). The clades 11 (7 cases) and 13 (6 cases) were involved only in multiple infections detected in urban. The types 35, 39, 59, 68 of HPV with high risk were isolated from multple infections. In rural, multiple infections with two HPV were detected. The citological screening by Babe-Papanicolaou examination was made only in 9 cases: HPV was not detected in 4 cases (one female had ASC-US: atypical squamous cells of "undetermined significance"); in 5 positive cases were detected HPV 16, 31, 58, 6.

Limited data are available describing human papillomavirus (HPV) genotype distribution among females with cytological abnormalities in Switzerland. Cervical cell specimens obtained from 5,318 women were screened routinely by liquid-based Pap smear. All specimens with cellular abnormalities were analyzed subsequently for HPV DNA by the Linear Array HPV genotyping test. Cellular abnormalities were found in 202 (3.8%) specimens, of which 150 (74.3%) were positive for high-risk (HR) HPV. HR-HPV was detected in 20 (60.6%; 95% CI, 43.7-75.4%) of 33 specimens with atypical squamous cells of undetermined significance compared to 98 (72.1%; 95% CI, 64-78.9%) of 136 low-grade squamous intraepithelial lesions and 32 (97%; 95% CI, 83.4-99.9%) of 33 high-grade squamous intraepithelial lesions. The cumulative prevalence of HR-HPV other than HPV 16 and 18 was significantly higher than HPV 16 and/or 18 lesions with atypical squamous cells and low-grade lesions and was comparable in high-grade squamous intraepithelial lesions. The most common HR-HPV genotypes were HPV 16 (15.2%), HPV 31 (12.1%), HPV 58 (12.1%), HPV 51 (9.1%), and HPV 59 (9.1%) in women with atypical squamous cells, HPV 16 (25%), HPV 51 (16.9%), HPV 52 (11.8%), HPV 31 (9.6%), and HPV 56 (8.1%) in women with low-grade lesions (LSIL) and HPV 16 (57.6%), HPV 18 (18.2%), HPV 31 (15.2%), HPV 52 (12.1%), and HPV 58 (6.1%) in women with high-grade lesions (HSIL).