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BackgroundCervical cancer disproportionately affects women ≥65 years, especially those not screened regularly. Speculum use is a key barrier.AimTo assess if offering non-speculum clinician-taken sampling and self-sampling increases uptake for lapsed attenders aged 50–64 years.Design and settingPragmatic randomised control trial conducted at 10 general practices in East London, UK.MethodParticipants were 784 women aged 50–64 years, last screened 6–15 years before randomisation. Intervention participants received a letter offering the choice of non-speculum clinician- or self-sampling. Control participants received usual care. The main outcome measure was uptake within 4 months.ResultsScreening uptake 4 months after randomisation was significantly higher in the intervention arm: 20.4% (n = 80/393) versus 4.9% in the control arm (n = 19/391, absolute difference 15.5%, 95% confidence interval [CI] = 11.0% to 20.0%, Pn = 120/393) versus control 13.6% (n = 53/391) (absolute difference 17.0%, 95% CI = 11.3% to 22.7%, Pn = 50/393) and control 13.6% (n = 53/391) arms. Ethnic differences were seen in screening modality preference. More White women opted for self-sampling (50.7%, n = 38/75), whereas most Asian and Black women and those from other ethnic backgrounds opted for conventional screening.ConclusionOffering non-speculum clinician-taken sampling and self-sampling substantially increases uptake in older lapsed attendee women. Non-speculum clinician sampling appeals to women who dislike the speculum but still prefer a clinician to take their sample. Providing a choice of screening modality may be important for optimising cervical screening uptake.

Purpose The study aimed to evaluate the diagnostic accuracy of polymerase chain reaction ‒based high-risk human papillomavirus (HPV) assays on self-collected vaginal and urine samples for detection of precancerous cervical lesions in referral population.Materials and Methods Women referred for colposcopy following abnormal cytology, were included this study. A total of 314 matched urine, vaginal, and cervical samples were collected. All samples were tested for HPV DNA using the RealTime HR-S HPV and Anyplex II HPV 28 assays. Primary endpoints were sensitivity for cervical intraepithelial neoplasia (CIN) 2+/CIN3+ and specificity for

Introduction p16 immunostaining is considered as a surrogate marker for human papillomavirus (HPV)-related head and neck squamous cell carcinomas (HNSCC). Herein, the utility of p16 is evaluated in cytology specimens. Material and methods The electronic data of a large academic institution was searched for cytology cases accompanied by p16 (2014-2018). Cases were categorized based on body sites. P16 staining was quantified (negative [0%], focal/patchy, or diffusely positive [>70%]). HPV testing was correlated where available. Results A total of 372 cases were included (male:female, 239:133). The largest differences in application of p16 between men and women were in head/neck cases (209 versus 59) and the abdominal cases (1 versus 33), respectively. p16 diffuse staining is seen in most squamous cell carcinomas, small cell carcinomas, and gynecologic serous carcinomas. p16 expression was patchy or negative in most adenocarcinoma, neuroendocrine carcinoma, spindle cell neoplasms, and benign conditions. HPV testing was done on 217 cases including 138 cases with strong p16 (127 HPV+/11 HPV−), 20 cases with focal/patchy P16 staining (6 HPV+/14 HPV−) and 59 cases with negative p16 staining (3 HPV+/56 HPV−). Conclusions Diffuse p16 staining aids in the diagnosis of HPV-related carcinomas, particularly HPV-related HNSCC, across the body and according to sex. In contrast, focal/patchy p16 staining does not correlate with HPV status across various body sites. In conclusion, intensity of p16 matters and should be correlated with cytomorphology, clinical history, and ancillary studies (eg, p40 immunostaining) for an accurate diagnosis and preventing diagnostic pitfalls.

Background Randomized controlled trials have shown a higher sensitivity and longer negative predictive value of high-risk human papillomavirus (HPV) testing than cytology for cervical cancer screening; however, little is known about the effectiveness of HPV testing in middle-income countries. Understanding the characteristics of HPV testing may increase the priority of HPV testing in health policies. The study aims to evaluate the effectiveness of HPV testing in the national cervical cancer screening programme in China. Methods We performed a nationwide, population-based study using individual data from the national cervical cancer screening programme in rural China between 2015 and 2017. The analyses included 1,160,981 women aged 35–64 years who underwent cytology alone or high-risk HPV testing with cytology or genotyping triage. The main outcome was cervical intraepithelial neoplasia 2 or worse (CIN2+). We used multivariate logistic regressions and performed sensitivity analyses with propensity score matching to compare the screening positive, colposcopy referral, detection rate, and positive predictive value (PPV). Results The screening positive rates for HPV testing and cytology were 10.1% and 4.0%, respectively. The per protocol colposcopy referral rate of HPV testing was significantly lower than that of cytology (3.5% vs 4.0%), and this difference was mostly due to the low referral threshold of cytology (≥ASC-US). Overall, HPV testing detected more CIN2+ (5.5 vs. 4.4 per 1000, adjusted odds ratio [aOR]=1.18, 95% confidence interval 1.11–1.25) and had a higher PPV (13.8% vs 10.9%, aOR 1.29, 95% CI 1.21–1.37) than cytology. The colposcopy referrals of HPV testing in comparison to cytology differed by income status; it significantly increased in lower-middle-income areas (3.7% vs 3.1%, aOR 1.21, 95% CI 1.17–1.25) and significantly decreased in upper-middle-income areas (3.4% vs 4.9%, aOR 0.69, 95% CI 0.67–0.71). Sensitivity analyses demonstrated the reliability and robustness of the results. Conclusions The introduction of HPV testing could improve both the CIN2+ detection rate and efficiency of cervical cancer screening programme, supporting the introduction of primary screening with high-risk HPV testing in China. Further study is needed to investigate the long-term effect of this change.

Objective Cervical cytology and Human papillomavirus (HPV) testing are effective screening techniques but both have limitations. A few recent studies in the literature have highlighted the role of co-expression of p16INK4a and Ki-67 for cervical cancer screening. The present study was undertaken to evaluate the diagnostic performance of the CINtec® PLUS kit (dual immunostaining for p16 and Ki-67) in SurePathTM liquid-based (LBC) cervico-vaginal samples. Materials and methods This was a prospective study performed on 52 cervico-vaginal SurePath™ LBC samples reported as having squamous epithelial cell abnormality (ECA). All the samples were stained using CINtec® PLUS kits. Additionally, HPV-DNA testing was also done and the results were compared. Results The age range was 34-74 years. ECA included 18 (34.6%) cases of ASC-US, 9 (17.3%) cases of low-grade squamous intraepithelial lesion (LSIL), 11 (21.2%) cases of high-grade squamous intraepithelial lesion (HSIL), and 14 (26.9%) cases of squamous cell carcinoma (SCC). Cervical biopsies were available in 19 (36.5%) cases. A total of 34/52 (65.4%) cases were positive for HPV-DNA (5/18-ASC-US; 6/9-LSIL; 10/11-HSIL; 13/14-SCC). The CINtec® PLUS test was positive in 41/52 (78.8%) cases (11/18-ASC-US; 6/9-LSIL; 11/11-HSIL; 13/14-SCC). On comparing CINtec® PLUS positivity (78.8%) with HPV positivity (65.4%), dual positivity was seen in 3/18 cases of ASC-US, 6/9 cases of LSIL, 10/11 cases of HSIL, and 12/14 cases of SCC. One case each of HSIL and SCC was negative on the HPV test and was positive on CINtec® PLUS. Conclusions CINtec® PLUS test helps to improve the detection of pre-cancerous cervical lesions as compared to cervical cytology or HPV testing alone and hence can serve as a potentially useful diagnostic and triage tool, especially for indeterminate cases.

The aim of this study was to investigate the prevalence of peritoneal human papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single-center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between March 2019 and April 2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV-DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. Two-hundred seventy-two patients had cervical and peritoneal HPV test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early stage, 28.8% in locally advanced cervical cancer (LACC) and 46.6% in the metastatic/persistent/recurrent setting (P = .001). No control patient was found to have peritoneal HPV infection. Higher frequency of PHP was documented in patients with larger tumor size (P = .003), presence of cervical HPV 16/18 genotypes (P

Testing for high risk human papillomavirus (HR-HPV) status is standard of care in squamous cell carcinomas of the oropharynx as well as cervical lymph node squamous cell carcinomas of unknown primary origin. DNA or RNA in-situ hybridization (ISH) and p16 immunohistochemistry, widely used currently for HPV detection are operator-dependent. In addition, DNA ISH has a relatively low sensitivity, and p16 is not entirely specific for HR-HPV infection. In this study, we examined the performance of the cobas® HPV genotyping assay in formalin-fixed, paraffin-embedded (FFPE) samples of head and neck squamous cell carcinoma. FFPE samples from head neck and other anatomic sites tested by ISH and p16 for HR-HPV at ARUP Laboratories were selected for this study. Samples were deparaffinized, stained and micro-dissected for tumor contents followed by tissue lysis, then tested with cobas® for HR-HPV. All the samples were also tested by HPV Linear Array for confirmation. All (N = 18) high risk HPV positive specimens tested by cobas® were confirmed as positive by the Linear Array test. All the specimens tested as negative by cobas® were tested as negative (N = 5) or positive only for low risk HPV (N = 3) by Linear Array, as cobas® only detects HR HPV. Limits of detection for HPV16 and 18 were established at 160-320 and 320-1600 copies, respectively. Our data suggest that cobas® HR-HPV genotyping is a viable option for detection of HR-HPV in formalin-fixed, paraffin-embedded samples from head and neck and other anatomic sites and has been validated for clinical use.

OBJECTIVE The goal of this study was to evaluate the performance of p16 staining in cell-blocks vs tissue specimens as a surrogate marker for human papillomavirus (HPV) status in oropharyngeal squamous cell carcinomas. METHODS Head and neck squamous cell carcinoma cases presenting as a neck mass with a p16 result on cytology and corresponding tissue specimens (1 January 2014 to 30 June 1920) were included in the study. The following were assessed from cell-block material: number of tumour clusters, percentage of tumour cells with p16 staining, and presence of staining in clusters vs single cells. Results were compared to tissue p16 status. Results of any other ancillary HPV testing were also noted. RESULTS Forty-two head and neck squamous cell carcinoma neck metastases (35 oropharyngeal, five non-oropharyngeal, and 2 unknown primaries) were identified. The p16 staining pattern in cell-blocks was seen in single cells (27.6%), clusters (44.8%), or both (27.6%). The percentage of tumour cells staining for p16 in cell-blocks was much lower than in corresponding tissue specimens. There were four false negatives and one false positive (concurrent HPV DNA polymerase chain reaction testing was positive in cytology and surgical material). CONCLUSIONS Compared to tissue, the cut-off for p16 interpretation in cell-blocks is substantially lower and staining may be present in single cells or clusters. In 96.9% of cases, any p16 staining in cell-blocks correlated with positive p16 staining in surgical specimens. However, a negative or discrepant p16 result on cell-block should prompt confirmatory HPV studies, as false negative p16 staining in cell-blocks is high.

Option recommended by World Health Organization (WHO) includes human papillomavirus (HPV) primary screening followed by visual inspection with acetic acid (VIA) triage. We implemented a program based on a 3T‐approach (Test‐Triage and Treat). Our objective was to verify the effectiveness of the program by defining a set of performance indices. A sensitization campaign was performed in Dschang (Cameroon) and women aged 30‐49 years were invited to participate for screening based on the 3T‐approach. Participants performed HPV self‐sampling (Self‐HPV), analyzed with the point‐of‐care Xpert HPV assay followed by VIA/VILI triage and treatment if required. Key performance indicators (KPIs) for screening, diagnosis, treatment and follow‐up were defined, and achievable targets were described for which the approach is likely to be running optimally. A total of 840 women with a mean age of 39.4±5.9 years participated. The KPIs included (i) the screening rate (8.4% at 7 months, target =20% at 12 months), (ii) HPV positivity rate (19.8%, expected range 18‐25%), (iii) compliance to referral to VIA/VILI and complete test (100%, target >90%), (iv) compliance to referral to thermal ablation (100%, target >90%), (v) VIA/VILI positivity rate (50.6%, expected range 45‐55%), (vi) a single visit from diagnostic to treatment (79.8%, target >80%), (vii) compliance to follow‐up at 1 month (96.4%, target >80%) and (viii) at 6 months (70.6%, target >80%). Program performance based on the single‐visit 3T‐approach corresponded to defined targets and preliminary results support adequateness of KPIs for periodic monitoring., The study shows the performance of screening for cervical cancer in a single visit, using the 3T strategy, for Test‐Triage and Treat in low‐income countries Our results will be of great interest especially those designing and conducting women’s health screening programs in low‐income countries. Improved primary screening, diagnosis, treatment, and follow‐up, such as in the single‐visit 3T approach to screen cervical cancer in Cameroon, will substantially reduce the incidence of preventable or treatable diseases in low‐ and middle‐income countries.

Background: Self sampled HPV testing is a cervical cancer screening method . However, cytology in self-sampled specimen cannot be used as a triage test. Therefore, other methods for triage should be considered. CyclinA1 (CCNA1) promoter methylation has strong association with cervical precancerous and cancerous lesion. The objective of this study was to compare the diagnostic value of CCNA1 and self-sampled specimen for detecting high-grade cervical intraepithelial lesions or worse (CIN2+). Materials and Methods: A cross sectional study was conducted. Women with abnormal cytology or positive for high risk HPV (hrHPV) indicated for colposcopic examination were enrolled. Self-collected sampling for hrHPV DNA (SS-HPV) and CCNA1 were performed. hrHPV DNA testing was done by Cobas 4800 method. CCNA1 promoter methylation was detected by CCNA1 duplex methylation specific PCR. Histopathologic result as CIN2+ obtaining from colposcopic directed biopsy or excisional procedure was considered as positive a gold standard. The results of hrHPV and CCNA1 were reported as positive or negative. Sensitivity specificity, positive predictive value, and negative predictive value of SS-HPV and CCNA1 were calculated by comparing the results with the gold standard. Results: Two hundreds and eighty women were recruited. High-grade cervical lesions and cervical cancer (CIN2+) were diagnosed in 21.8% (61 cases) of the patients. The most common type of hrHPV was non 16, 18 subtype, followed by HPV16 and 18. CCNA1 was positive in 13 patients out of whom, twelve were CIN2+. Sensitivity of CCNA1 was 19.7 % and its specificity and accuracy were 99.5% and 82.14%, respectively. The sensitivity of SS-HPV was 70.5%, and its specificity and accuracy were 39.2% and 43.3%, respectively. Conclusion: Due to high specificity and positive predictive value of CCNA1, it can be used as alarming sign of having high-grade cervical intraepithelial lesions, especially in patient who has positive hrHPV DNA test based on self-collected sampling.

Human papillomavirus (HPV) testing is highly sensitive compared to cytology, with the trade‐off of being less specific. We investigated whether select combinations of HPV genotypes, ascertained by Linear Array (LA) and Xpert HPV (GX), can optimize sensitivity/specificity trade‐offs to detect high‐grade cervical intraepithelial neoplasia (CIN2+). In a study in Cape Town, South Africa, 586 women living without and 535 living with HIV, aged 30‐65 years, were recruited. Each woman underwent a pelvic exam to collect cervical samples (tested by LA and GX for 14 high‐risk HPV genotypes) and underwent colposcopy with histological sampling to determine CIN2+. In multivariable logistic regression of LA results, only HPV genotypes 16, 18, 31, 33, 35, 52, 58 were significantly associated with CIN2+ (P, Human papillomavirus (HPV) testing is highly sensitive compared to cytology, with the trade‐off of being less specific. Among South African women, we have shown that restricting the definition of screen‐positive to women with HPV genotypes 16/18/45/31/33/35/52/58 substantially improves the specificity of screening while producing only minor reductions in sensitivity compared to inclusion of all 14 HPV genotypes conventionally included as high risk in HPV assays.

OBJECTIVE Micronuclei counts were performed in cervical smears with low-grade squamous intraepithelial lesions of the cervix (LSIL) to assess its potentiality as tumour marker in cervical carcinogenesis. METHODS The cases studied were from the ongoing rural cervical cancer screening in west Lucknow, India. Micronuclei counts were performed in the cervical smears of 100 LSIL cases, and the number of cells with micronuclei was defined as micronucleated cells (MNC) and the number of micronuclei per 1000 cells as MNC score. Human papillomavirus (HPV) DNA testing was also done in 100 LSIL cases by GeneNav qPCR test. RESULTS A high MNC score was found in 20 of the 100 LSIL cases while the counts were low in the remaining 80. Persistence of LSIL was seen in 19 of the 20 LSIL cases with high MNC score while only six cases of the 80 cases with low MNC score showed persistence. The persistence of LSIL was very high in cases with high MNC score. The multiple high-risk HPV types such as 18, 31, 33 and 35 were seen in 12 of the 100 LSIL cases and a high positivity rate was seen in women with high MNC score. The persistence of LSIL was also higher with HPV positivity. CONCLUSION The study revealed correlation between high MNC score, persistence of LSIL and HPV positivity. Hence, MNC score can prove to be very useful in discriminating high-risk LSIL cases that are less likely to regress and possibly may progress to high-grade squamous intraepithelial lesions or carcinoma.

Background To adopt HPV self-sampling in Japan, we assessed the concordance between self- and physician-collected human papillomavirus (HPV) samples from Japanese patients and examined the performance of HPV self-sampling for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Methods Patients who had previously tested negative for intraepithelial lesions or malignancy/HPV-positive, and patients with atypical squamous cells of undetermined significance or worse (ASCUS+) cytology were eligible for this cross-sectional study. Participants performed HPV self-sampling using an Evalyn brush, which was submitted at the Fukui Prefectural Health Care Association. The Evalyn brush heads were stored in ThinPrep vials. The physician, however, performed HPV and cell sampling using an endocervical brush and immediately stored the brush heads in ThinPrep vials. All participants underwent colposcopy and biopsy. Histopathological diagnoses were made by pathologists at Fukui University Hospital. HPV infection was confirmed using a PCR-based Cobas 4800 HPV DNA test. Cytological analysis was performed at Fukui Prefectural Health Care Association. Results HPV-positive rates for physician-collected samples and self-collected samples were 51 and 50%, respectively. The perfect match rate of HPV type between the groups was 88% (κ = 0.76). HPV16/18 showed higher agreement rates than other HPVs (99%, kappa 0.96 and 89% kappa 0.77, respectively). Both groups showed 100% sensitivity to CIN2+, but specificity was 57.0 and 58.1%, respectively. Conclusion For HPV typing, a good concordance rate was seen between self- and physician-collected samples. Self-sampling showed high sensitivity for CIN2+. Self-sampling using the Evalyn brush and Cobas 4800 may be feasible for screening Japanese individuals.

We assessed the prevalence of HPV DNA in a large series of Chinese penile cancer and examine its association with the histological subtype, p16INK4a expression, and prognosis. We pathologically categorized 226 invasive penile squamous cell carcinomas and assessed HPV genotyping by real-time PCR and p16INK4a immunohistochemistry. The results were correlated with histopathological and clinical parameters and disease-specific survival (DSS). HPV DNA was detected in 32.7% (74/226) of penile cancer cases. The most frequent genotype was HPV 16 (64/74, 86.5%), followed by HPV 18 (6/74, 8.1%). Fifty-nine (26.1%) cases were positive for the p16INK4a expression, and p16INK4a expression had a sensitivity of 56.8% (95% CI, 45.2–68.3%) and a specificity of 88.8% (95% CI, 83.8–93.9%) for defining HPV status. HPV DNA (P = 0.019), p16INK4a (P = 0.038), age (P = 0.018), grade of differentiation (P = 0.001), lymph nodes (P

Despite the common perception that the human papilloma virus (HPV) is a requirement for the development of cervical cancer (CC), a considerable number of CCs test HPV negative. Presently, many countries are shifting to HPV primary CC screening, and it is of importance to increase the knowledge about the group of CCs that test HPV negative. The aim of this study was to reinvestigate a proportion of cervical tumors with a primary negative or invalid test result. Reinvestigation with repeated genotyping (targeting L1) was followed by analysis with an alternative target method (targeting E6/E7) on existing or additional tumor material. Consistently negative tumors were histologically evaluated, and cases with low or lacking tumor cell content, consistent invalid test results, or with suspicion of other than cervical origin were excluded. HPV-negative cases were thereafter subjected to immunohistochemistry (Cytokeratin 5, pan cytokeratin, protein 63, P16, and P53). The HPV-negative proportion could after reinvestigation be reduced by one-half (14%-7%). Additional positive samples were often detected in late polymerase chain reaction cycles, with an alternative (E6/E7) or the same (L1) target, or with a method using shorter amplicon lengths. Confirmed HPV negativity was significantly associated with worse prognosis, high patient age, longer storage time, and adenocarcinoma histology. Some of the HPV-negative cases showed strong/diffuse p16 immunoreactivity, indicating some remaining false-negative cases. False HPV negativity in this cohort was mainly linked to methodological limitations in the analysis of stored CC material. The small proportion of presumably true HPV-negative adenocarcinomas is not a reason for hesitation in revision to CC screening with primary HPV testing.

How to manage human papillomavirus (HPV)-positive women in cervical cancer screening remains debated. Our study compared different strategies to triage HPV positivity in a large cohort of women participating in a population HPV-based screening program. Women were tested for HPV (Cobas 4800; Roche), and those positive were triaged with cytology; cytology-positives were referred to colposcopy, while negatives were referred to 1-year HPV retesting. All HPV-positive women were also evaluated with p16/ki67 dual staining (Roche). All lesions found within 24 months of follow-up were included in the analyses. Of the 70 146 women tested, 4757 (6.8%) were HPV-positive. Of these, 1090 were cytology-positive and were referred to colposcopy. Of the 2958 HPV-positive/cytology-negative women who presented at 1-year retesting, 1752 (59.9%) still tested positive. Cumulatively, 532 CIN2+ (including 294 CIN3+) were found. The sensitivity of cytology, HPV16/18 and p16/ki67 as triage test for CIN3+ was 67.9%, 56.0% and 85.0%, respectively. The positive predictive value (PPV) for immediate colposcopy referral was 21.0%, 15.8% and 22.9%, respectively. Combining cytology with typing increased sensitivity to 83.9% and lowered PPV to 14.8%, while combining p16/ki67 and typing increased sensitivity to 91.1%, lowering the PPV to 15.9%. Women negative to p16/ki67 triage presented a cumulative 1-year CIN3+ risk of about 1%. In conclusion, when triaging HPV positivity, p16/ki67 performed better than cytology with or without HPV16/18 genotyping. The strategies that included dual staining achieved sensitivity and low 1-year risk for CIN3+ sufficiently high enough to permit considering extending the surveillance interval to 2 to 3 years for HPV-positive/triage-negative women.

Our objective was to evaluate the pathologic features and clinical outcomes in cases of invasive penile squamous cell carcinoma (SCC) and the association with p16 immunohistochemistry (IHC) and human papilloma virus (HPV) in situ hybridization (ISH). A retrospective multi-institutional database search was conducted for invasive SCC of the penis diagnosed between 2007 and 2018 that had undergone surgical resection. Pathologic features, p16 IHC, and HPV ISH were investigated with clinical outcomes. A total of 102 patients were included in the study. The average age was 63 ± 13.3 years. Based on histology, 46% of tumors displayed an HPV-related subtype, whereas p16 was positive in 52% of all cases. Tumor histology correlated well with p16 positivity (P .001), and p16 IHC accurately predicted the presence of HPV in 25/26 (96%) cases. On multivariate analysis, perineural invasion was associated with local disease recurrence (P = .02), whereas lymphovascular invasion was associated with progression to metastatic disease (P = .002) and increased overall mortality (P = .02). Urethral involvement was also associated with increased overall mortality (P = .02). In addition, HPV-related tumors based on histologic features correlated with lower rates of metastatic disease (P = .007). HPV is a common cause of penile SCC and can be diagnosed by tumor histology and confirmed by overexpression of p16 on IHC. The presence of lymphovascular invasion, perineural invasion, and urethral involvement are poor prognostic indicators, whereas HPV-related tumors based on histology may have lower risk for metastatic disease.

br /Using HPV testing to triage ASC-US still has some problems of unnecessary colposcopy in many cases. A previous study reported that methylation of CCNA1, a tumor suppressor gene, can differentiate between low and high grade lesions. This study was designed to evaluate the diagnostic values and application of CCNA1 methylation in the patients with ASC-US group.br /Materials and methods:br /Cross sectional analytic study was conducted in the patients withbr /ASC-US cytology. HPV DNA testing and CCNA1 promoter methylation testing were performed. The patients were sent for colposcopic examination and biopsy. Biopsy results were considered as gold standard. Diagnostic test of HPV test and CCNA1 methylation test were calculated for sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), likelihood ratio for test positive and negative and 95% confidence interval.br /Results:br /One hundred and seventy patients were enrolled. Mean age was 39.7 years old. HR-HPV was positive in 70% of the patients. HPV type 16, type 18 and non-16,18 were 12.4%, 4.7% and 42.4%, respectively. CIN2+ were found in 12.4% (21 cases). CCNA1 promoter methylation was positive in 5 cases. CCNA1 had high specificity 99.3%, NPV 89.2% and PPV 80% in detection of CIN2+ but sensitivity was 19%. Likelihood ratio for positive test was 28.4 and likelihood ratio for negative test was 0.8. HPV test had sensitivity of 90.5% and NPV of 95.9% but low specificity and PPV as 31.5% and 15.7%, respectively.br /Conclusion:br /CCNA1 promoter methylation testing had very high specificity, likelihood ratio for the positive test and PPV (99.3%, 28.4 and 80.0, respectively). Therefore, CCNA1 promoter methylation test may be used in the HPV DNA positive cases to classify the urgency of colposcopy and the colposcopist should pay more attention to CCNA1 positive patients because of their higher chance to identify the significant lesions.

Background The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution. Methods Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations. Results Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively). Conclusions Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

This study aimed to determine the prevalence of HPV genotypes in genital warts among women in Harare, Zimbabwe. Women aged 18-45 years attending gynaecology and genitourinary clinics with a clinical diagnosis of genital-warts were recruited. HPV-DNA was extracted from tissue biopsies. HPV-DNA testing and typing was done by Southern Dot Blot Hybridisation. A hundred samples from 100 women were analysed. Median age of participants was 30.3 years (range 18-45 years). Seventy-eight percent of participants were HIV infected. HPV prevalence was 98%. Low risk genotypes predominated at 86% prevalence. The most prevalent genotypes were 11 (47%), 6 (42%) and 16 (14%). This is the first study on HPV genotype distribution among women with genital warts in Zimbabwe. The high prevalence of HR-HPV 16 in clinically benign lesions shows that warts should have histological analysis to exclude pre-malignancy and malignancy.Impact statement

Background/Aims: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigat ed. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. Methods: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this ret rospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were per formed. Results: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3-4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, perfor mance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respective ly). Furthermore, HPV genotype 18 positivity was also an independent poor prog nostic factor of OS (HR, 10.87, p < 0.001). Conclusions: Non-oropharyngeal cancer, poor performance status, and HPV gen otype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

Objective: To assess the psychosocial impact of human papillomavirus (HPV) testing, colposcopy, and Pap-smear, as triage strategies after a Pap-smear with atypical squamous cells of undetermined si...

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25–29 years to 5.1% for women aged 50–60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25–29) to 76.3% (for women 40–49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

BACKGROUND Many patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HPV-HNSCC) initially present with cervical lymph node metastases. Although p16 immunohistochemistry (IHC) is the most commonly used surrogate marker for HPV, however criteria in cytologic material are not well established. The objective of this study was to better characterize p16 IHC in cell blocks of metastatic HPV-HNSCC, and to evaluate the performance of HPV RNA in situ hybridization (RNA ISH). METHODS p16 IHC was performed on cell blocks from 97 metastatic HPV-HNSCC fine-needle aspiration specimens with HPV status confirmed by DNA or RNA ISH or polymerase chain reaction (PCR). Tumor cellularity ( 500 cells) and quality (presence of cell clusters, necrosis) were recorded. p16 staining intensity and extent (1%-9%, 10%-69%, and ≥70%) were scored. In addition, RNA ISH was performed on 38 PCR-positive cases. RESULTS p16 IHC was positive in 90 of 97 cases (93%), demonstrating variable patterns. p16 staining was found to be moderate to strong in 69 cases, with 37 cases (38%) demonstrating positivity in ≥70% of tumor cells. Weak staining occurred in 21 cases (22%) and 7 cases (7%) were negative. Of the 60 cases with weak and/or absent expression or staining in

Background The Hybrid Capture 2 (HC2) High-Risk HPV DNA assay serves as a triage test in the Slovenian national cervical cancer screening programme ZORA. To improve the limited analytical accuracy of HC2 test results near the cut-off value (1.0 relative light units/cut-off (RLU/CO)), we follow an internal protocol of repeating the test on all samples with borderline results within the 0.7-2.0 RLU/CO interval. The aim of the study was (i) to determine the clinical relevance of HC2 test results within three different “grey zones” for samples stored in Specimen Transport Medium (STM) and (ii) to determine whether the current algorithm of retesting “grey zone” STM specimens with the HC2 assay is clinically relevant. Patients and methods The study included 594 women between 20 and 65 years of age. All participating women were referred for colposcopy, and in cases of abnormal results, biopsy was performed. We assessed the distribution of HC2 test results and the corresponding proportion of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) lesions in three different “grey zones” (1.0–2.5, 0.4–4.0 and 0.7–2.0 RLU/CO), retested specimens with results within a 0.4–4.0 RLU/CO interval and calculated the sensitivity and specificity for HC2 at different RLU/CO values. Results The proportion of specimens within 1.0–2.5, 0.4–4.0 and 0.7–2.0 RLU/CO intervals was 3.9%, 10.8% and 4.5%, respectively. The proportion of CIN2+ lesions within these “grey zones” was 2.5%, 5.6% and 1.2%, respectively. Retesting the samples did not detect any additional CIN2+ cases. Within the 1.0–2.5 RLU/CO interval, the sensitivity decreased from 93.8% to 91.4%, while the specificity increased from 63.3% to 67.5%; for the 0.4–4.0 RLU/CO interval, the sensitivity decreased from 95.1% to 89.5%, while the specificity increased from 56.8% to 69.4%; and for the 0.7–2.0 RLU/CO interval, the sensitivity remained nearly constant (94.4 vs. 93.2%), while the specificity increased from 60.6% to 66.4%. Conclusions Our results show that retesting STM samples within the “grey zones” is not necessary. Retesting samples in the negative “grey zone” does not increase sensitivity, and retesting in the positive “grey zone” is not followed by a less intensive management of women, since these women are recalled regardless of the results of the retest. Furthermore, the majority of samples retain the original HC2 results after retest, and the number of CIN2+ lesions among women with “grey zone” HC2 results is low.

Since the introduction of the Papanicolaou (Pap) smear system in 1943, cervicovaginal cytology has been used as a standard screening test for cervical cancer. The dissemination of this test contributed to reductions of the incidence and mortality of cervical cancer worldwide. In Korea, regular health check-ups for industrial workers and their family members were introduced in 1988 and were performed as part of the National Cancer Screening Program in 1999. As a result, the incidence of cervical cancer in Korea has been steadily decreasing. However, about 800 cases of cervical cancer-related deaths are reported each year due to false-negative test results. Hence, new screening methods have been proposed. Liquid-based cytology (LBC) was introduced in 1996 to overcome the limitations of conventional Pap smears. Since then, other LBC methods have been developed and utilized, including the human papilloma virus test—a method with higher sensitivity that requires fewer screenings. In this study, we review current issues and future perspectives related to cervical cancer screening in Korea.

The interpretation of atypical glandular cells (AGCs) remains a major challenge in gynecologic cytopathology using liquid-based cytology (LBC) (ThinPrep and SurePath). The comparison of performance of detecting glandular abnormalities using these 2 methods is lacking. We investigated the reporting rates of AGCs, human papillomavirus (HPV) testing, and histologic follow-up results in ThinPrep (TP) and SurePath (SP) samples.In our institution, both TP and SP were utilized during the period between January 2014 and June 2017. A retrospective search was conducted to identify patients with AGCs from 58,591 LBCs (27,041 TP and 31,550 SP). Roche (Pleasanton, CA) cobas HPV testing and histologic follow-up results were collected.The reporting rates of AGCs for TP (0.7%) or SP (0.2%) were within the College of American Pathologists benchmark ranges, but the reporting for TP was significantly greater than that for SP (P0.0001). The HPV-positive rates were 26.0% and 19.4% in TP-AGCs and SP-AGCs, respectively, with no statistical significance. A total of 137 (74.9%) TP-AGCs and 54 (74%) SP-AGCs had histologic follow-up. High-grade squamous intraepithelial lesions (HSIL)/squamous cell carcinoma were identified in 8.8% (12 of 137) of TP-AGCs and 13% (7 of 54) of SP-AGCs. Adenocarcinomas including endocervical and endometrial adenocarcinomas were identified in 9.5% (13 of 137) of TP-AGCs and 13% (7 of 54) of SP-AGCs. Together, 18.2% (25 of 137) of TP-AGCs and 25.9% (14 of 54) of SP-AGCs showed either HSIL or carcinoma in histologic follow-up, but with no statistical significance.TP preparation detected considerably more AGCs than SP preparation. There was no statistical significant difference in HPV-positive rates or histologic follow-up outcomes between TP-detected AGCs and SP-detected AGCs.

BACKGROUND The aim of this study was to assess the presence of HPV DNA in cervical tissues and lymph nodes in patients who have uterine cervical neoplasms with lymphatic metastases and who underwent surgery for invasive cervical cancer and pelvic lymphadenectomy, to establish the utility of HPV type and viral load in predicting disease progression. MATERIAL AND METHODS We retrospectively assessed 88 patients with uterine cervical neoplasms with lymph node metastases. All 88 patients were in FIGO stage IA-IIB. A total of 316 paraffin-embedded archival tissues (88 cervical samples and 228 pelvic lymph node specimens) were acquired. All the samples were analyzed using real-time PCR to determine HPV DNA presence/type and to quantify viral load. RESULTS In total, 17 HPV genotypes were detected in the cervical lesions and pelvic lymph nodes of the patients. The most common HPV type in all samples was HPV16, followed by HPV18. The existence of HPV16 DNA and low HPV16 viral load in cervical lesions were also significantly associated with disease recurrence. Furthermore, lymphovascular space involvement was also correlated with worse disease outcome. CONCLUSIONS HPV16 DNA presence and low viral load in primary lesions can be used to predict disease recurrence. HPV DNA is a favorable prognostic indicator in patients with uterine cervical neoplasms who have lymphatic metastases.

Introduction: Visual inspection of the cervix with acetic acid is used to control the burden of cervical cancer in low- and middle-income countries. This method has some limitations and HPV DNA testing may be an alternative, but it is expensive and requires a laboratory setup. Cheaper and faster HPV tests have been developed. This study describe the agreement between a fast HPV test (careHPV) and hybrid capture 2 (HC2) in detection of high-risk HPV among Tanzanian women. Material and methods: The study involved women attending routine cervical cancer screening at the Ocean Road Cancer Institute and Kilimanjaro Christian Medical Centre in Tanzania. The women were offered HIV testing. Two cervical samples were subsequently obtained; the first sample was processed at the clinics using careHPV and the second sample was transported to Denmark and Germany for cytology and HC2 analysis. Kappa statistic was calculated to assess the agreement between careHPV and HC2. The sensitivity, specificity and predictive values of careHPV were calculated using HC2 as reference. The analyses were done for the overall study population and stratified by testing site and HIV status. Results: A total of 4080 women were enrolled, with 437 being excluded due to invalid information, lack of careHPV or HC2 results. Overall agreement between the tests was substantial with a kappa value of 0.69 (95% confidence interval [CI] 0.66-0.72). The sensitivity and specificity of careHPV was 90.7% (95% CI 89.6-91.8) and 84.2% (95% CI 81.2–86.8), respectively. The agreement was similar in the stratified analyses where the kappa values were 0.75 (95% CI 0.70-0.79) in women aged 25-34, 0.66 (95% CI 0.62-0.70) in women aged 35–60, 0.73 (95% CI 0.70-0.77) at the Ocean Road Cancer Institute, 0.64 (95% CI 0.60-0.69) at the Kilimanjaro Christian Medical Center, 0.73 (95% CI 0.68-0.79) in HIV-positive and 0.66 (95% CI 0.63-0.70) in HIV-negative women. The kappa value of 0.64 (95% CI 0.39-0.88) for cervical high-grade lesions indicates a substantial agreement between careHPV and HC2 in detecting HPV among women with cervical high-grade lesions. Conclusions: A substantial agreement was found between careHPV and HC2 in detecting HPV overall as well as detecting HPV among women with cervical high-grade lesions. However, given the limited resources available in low and middle-income countries, the HPV testing assay should be weighed against the cost-effectiveness of the test.

Background Human papillomavirus (HPV) is a primary risk factor for cervical cancer. HPV 16 and 18 are the two most carcinogenic genotypes and have been reported in the majority of cervical cancer. High-risk HPVs (hrHPVs) other than HPV 16/18 cause approximately a quarter of cervical cancers. We aimed to present the colposcopy-guided biopsy results of non-16/18 hrHPV-infected women with negative cytology. Methods This is a retrospective cohort study conducted on 752 patients between the ages of 30-65 years with non-16/18 hrHPV and negative cytology undergoing colposcopy-guided biopsy at a tertiary gynecological cancer center between January-2016 and January-2019. Results The mean age of the women was 42.35±9.41 years. Cervical intraepithelial neoplasia (CIN) 2+ lesion was detected in 49 (6.5%) women with negative cytology. The rate of CIN 2+ lesions in women with abnormal cytology was 12.8%. Patients with abnormal cytology had about 2.1 and 2.4 times increased the odds of CIN 2+ lesion in cervical biopsy and endocervical curettage specimens, respectively. CIN 3+ lesion was detected in 20 (2.7%) women with negative cytology. One (0.1%) of the patients with HPV 39 and negative cytology had invasive cervical cancer. The two most common HPV subtypes were HPV 31 and HPV 51. Conclusions The risk of cervical preinvasive lesions still can be detected and cannot be completely eliminated among hrHPV other than 16/18-infected women with negative cytology. Based on the results of this study, referral of non-16/18 hrHPV-infected women with negative cytology to colposcopy is supported as a credible and feasible strategy.

OBJECTIVE To investigate if a self-obtained vaginal sample (SOVAS) contains sufficient DNA for a human papillomavirus (HPV) test and if the results are comparable to those obtained via cervical samples (CS) collected by a physician. METHODS One hundred and fifty-one women who had abnormal cervical smears or who were HPV-positive were enrolled. Self-sampling was done after reading instructions and watching a 2-min-long video, whereas CS was obtained with a cervical cytobrush during a gynecologic examination. RESULTS A multiplex real-time polymerase chain reaction-based assay detected the prevalence of any type of HPV to be 67.5% in the SOVAS and 57.4% in the CS, and that of high-risk (HR-) HPV to be 58.7% in the SOVAS and 48.6% in the CS. The sensitivity of detection of HR-HPV in the SOVAS was 100% (95% confidence interval [CI] -0.09 to 0.32) for high-grade squamous intraepithelial lesion, 78% (95% CI -0.09 to 0.13) for atypical squamous cells of undetermined significance or worse, and 95% (95% CI -0.01 to 0.25) for low-grade squamous intraepithelial lesion or worse, which was statistically within the non-inferiority margin compared with that of CS. CONCLUSION Our study shows that the collection of a SOVAS is feasible and it is comparable to a CS for HPV DNA testing. Future studies are required to investigate the feasibility and cost-effectiveness of a mail-delivered SOVAS for cervical cancer screening.

IntroductionEvidence supports high-risk human papilloma virus (HPV) testing as the primary cervical cancer screening tool. However, benefits and harms should be carefully considered before replacing liquid-based cytology. In women age 50 and older, we evaluated how a commercially available DNA amplification HPV test compares with routine liquid-based cytology.MethodsThis prospective study included 4043 patients who had a cervical sample analyzed from September 2011 to September 2012. Patients were followed between 64 and 76 months (median: 70 months). Samples were analyzed using both liquid-based cytology and the Cobas 4800 HPV DNA test. We calculated the diagnostic efficacy of liquid-based cytology and HPV, with or without the opposite test as triage, using cervical intraepithelial neoplasia (CIN2+/CIN3+) as reference.ResultsThe patients had a median age of 58 years, (range; 50–90). At baseline, HPV prevalence was 8.0%: a total of 3.7% of patients had atypical squamous cells of undetermined significance or worse (ASCUS+). Positive test results were 1.9% for liquid-based cytology with HPV triage and 3.0% for HPV with liquid-based cytology triage. The cumulative incidence of CIN3+ was 1.0% (40/4043). Sensitivities for CIN3+ were: liquid-based cytology 47.5% (31.5%–63.9%); liquid-based cytology with HPV triage 45.0% (29.3%–61.5%); HPV 90.0% (76.3%–97.2%); and HPV with liquid-based cytology triage 67.5% (50.9%–81.4%). Corresponding specificities were: liquid-based cytology 96.6% (96.0%–97.2%); liquid-based cytology with HPV triage 98.5% (98.0%–98.8%); HPV 92.8% (92.0%–93.6%); and HPV with liquid-based cytology triage 97.7% (97.2%–98.1%). At baseline, HPV testing overlooked five cases of gynecological cancer other than cervical cancer. Five cervical cancers were detected, two had been overlooked at baseline by liquid-based cytology and two by HPV testingConclusionHPV screening using DNA amplification is a promising alternative to liquid-based cytology in women age 50 and older, but evaluation of alternative triage methods is warranted. The risk of overlooking cancers needs consideration when replacing liquid-based cytology with HPV testing as a method for primary screening.

Objective We aim to compare the cost‐effectiveness of the old cytology programme with the new high‐risk human papillomavirus (hrHPV) screening programme, using performance indicators from the new Dutch hrHPV screening programme. Design Model‐based cost‐effectiveness analysis. Setting The Netherlands. Population Dutch 30‐year‐old unvaccinated females followed up lifelong. Methods We updated the microsimulation screening analysis (MISCAN) model using the most recent epidemiological and screening data from the Netherlands. We simulated both screening programmes, using the screening behaviour and costs observed in each programme. Sensitivity analyses were performed on screening behaviour, utility losses and discount rates. Main outcome measures Cervical cancer incidence and mortality rates, number of screening tests and repeat tests, colposcopy referrals by lesion grade, costs from a societal perspective, quality‐adjusted life years (QALYs) gained and cost‐effectiveness. Results The new Dutch cervical cancer screening programme decreased the cervical cancer mortality by 4% and the incidence by 1% compared with the old programme. Colposcopy referrals of women without cervical intra‐epithelial neoplasia grade 2 or worse, increased by 172%, but 13% more QALYs were still achieved. Total costs were reduced by 21%, mainly due to fewer screening tests. Per QALY gained, the hrHPV programme cost 46% less (€12,225) than the cytology programme (€22,678), and hrHPV‐based screening remained more cost‐effective in all sensitivity analyses. Conclusions The hrHPV‐based screening programme was found to be more effective and cost‐effective than the cytology programme. Alternatives for the current triage strategy should be considered to lower the number of unnecessary referrals. Tweetable abstract First results after implementation confirm that HPV screening is more cost‐effective than cytology screening., Tweetable abstract First results after implementation confirm that HPV screening is more cost‐effective than cytology screening.

Immunosuppression is a risk factor of persistent human papillomavirus (HPV) infections, which might lead to development of (pre)malignant lesions of the cervix and lower anogenital tract. Results of HPV DNA testing using cervicovaginal self-samples are comparable to those that are clinician-obtained and therefore might be used in cervical screening. The aim of this study was to assess the prevalence of high-risk HPV (hrHPV) infections, their risk factors and the genotypes distribution among women undergoing immunosuppressive therapy. Women undergoing immunosuppressive therapy for at least three months due to solid organ transplantation or autoimmune disorders were asked to self-collect samples for HPV testing using cervicovaginal brushes and complete questionnaires regarding cervical cancer risk factors. HPV DNA detection and genotyping were performed using Genotyping kit HPV GP version 2. hrHPV was detected in 26/90 (28.9%) specimens. Genotyping revealed a broad range of hrHPV, with type 16 being the most common genotype (11/26). The components of bivalent/quadrivalent or nonavalent vaccines cover all genotypes present in 4.4% and 17.8% women, respectively, and occur as a co-infection with other types in 12.2% and 23.3% of women, respectively. The only feature significantly associated with being hrHPV-positive was having at least two lifetime sexual partners. The high prevalence of hrHPV infections among immunosuppressed women emphasizes the need for regular cervical cancer screening with HPV DNA testing, which might be performed on self-collected specimen.

Background In recent years, several high‐risk human papillomavirus (HR‐HPV) tests have been developed. The assay capabilities need to be systematically reviewed. Here, we compared the clinical sample performance of three novel HR‐HPV assays (Liferiver, Yaneng, and Darui) based on different platforms with the widely adopted cobas4800 test. Methods A total of 346 cervical swabs from women who were screened for cervical cancer were analyzed for the presence of 14 HR‐HPV genotypes. The distinction between the four assays was investigated by the genotyping and direct sequencing. Results The positive rates of the four assays ranged from 61.56% to 64.16%. The overall concordance was 88.15%. The Yaneng assays displayed the best sensitivity (100%) and specificity (98.43%). The sensitivity (98.17%) and specificity (98.43%) of the Darui assay were superior to those of the cobas4800 test (97.72% and 93.70%, respectively). The Liferiver assay displayed comparable sensitivity with the cobas4800 test (95.89% and 97.72%, respectively). The specificity of the cobas4800 was lower than that of the Liferiver assay (93.70% vs. 97.64%). Conclusions The three novel HR‐HPV assays displayed good agreement with the cobas4800 test. The analytical performance of all four fulfilled the requirements of sensitivity and specificity for HR‐HPV detection., In this research, we have compared the clinical sample performance of three novel HR‐HPV assays (Liferiver, Yaneng, and Darui) based on different platforms with the widely adopted cobas4800 test, and the distinction between the four assays was investigated by the genotyping and direct sequencing.

In the US, 60% to 80% of oropharyngeal squamous cell carcinomas (OPSCCs) are associated with human papillomavirus (HPV). However, until recently, no consensus existed about when and how to test for HPV in patients with head and neck cancers. We aimed to evaluate the use of p16 and HPV testing at our institution because p16 immunohistochemistry is reportedly a reliable surrogate marker for HPV detection in OPSCCs. Methods We identified all cases at our institution of primary or metastatic squamous cell carcinoma (SCC) of the head and neck with a concurrent p16 immunostain analysis from January 1, 2013, through August 31, 2018. Patient demographic data, tumor characteristics, p16 result, and any HPV result (in situ hybridization and E6 and E7 RNA test) were captured. Results We identified 104 patients. Most primary tumors (53/57 [93.0%]) and metastases (40/47 [85.1%]) were positive for p16. Thirty-seven cases (35.6%) had reflex high-risk HPV (HR HPV) testing performed. Of the 35 p16-positive cases, 6 had discrepant HR HPV results (p16+ /HPV- ). We identified 47 p16 immunostains that were performed on lymph nodes with primary tumors of unknown origin. Most were cytology cases (34/47 [72.3%]), and most were p16 positive (40/47 [85.1%]). Neither tumor differentiation nor tumor keratinization was predictive of p16 positivity. Tumors with basaloid differentiation were universally p16 positive. Conclusion p16 immunohistochemistry accurately identifies HPV-positive OPSCC. Cytology specimens have an important role in characterizing SCC of unknown origin. HR HPV testing is not routinely required, and results may be discrepant with p16 findings.

Background The 2012 American Society for Colposcopy and Cervical Pathology Consensus Guidelines provide information for managing abnormal cervical cancer screening tests and cancer precursors. According to these guidelines for Pap smear diagnosis of Atypical squamous cells of undetermined significance, reflex high risk (HR) human papilloma virus (HPV) genotyping is required among women 21 years of age or older. Whereas, in women of 30 to 65 years of age, HR-HPV can be ordered by the clinicians as part of co-testing with any diagnosis and every 5 years with a negative Cervico-Vaginal Pap test (CVPT). Methods A retrospective review of the CoPath database of the Pathology Department at the University of Florida, College of Medicine Jacksonville, FL, was performed to identify North Florida (NF) women who underwent CVPT and HR-HPV testing between 2006 and 2014. The women were stratified by race and age, respectively. Results The study included 19,933 CVPTs. Significant differences in the outcomes' distributions were found among age and race groups, respectively. Highest prevalence of HPV positivity was found in African American women, and in 14- to 20-year-old women, respectively. Twenty- to 30-year-old women had the highest percentage (59%) of epithelial abnormality. The most common HR-HPV genotypic distribution was other HR-HPV. Conclusions This study underscores the importance of using both HR-HPV and CVPT for screening for cervical cancer, and confirms the need for special focus on managing high-risk populations subgroups, such as African American women, and women of ages 14 to 20 years especially in high-risk populations.

To identify the optimal cost-effective strategy for cervical cancer screening program in Thailand by comparing the different algorithms which based on the use of primary human papilloma virus (HPV) assay. We use a Microsoft Excel–based spreadsheet to calculate the accumulated cases of preinvasive and invasive cervical cancer and the budget impact of each screening program. The model was developed to determine the cost-effectiveness of 3 screening strategies: pooled HPV test with reflex liquid-based cytology triage, HPV genotyping with reflex p16/ki67 dual stain cytology, and pooled HPV test with dual stain. The main outcomes were the total cost, incremental quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Strategy entailing primary HPV genotyping and reflex dual stain cytology is the least costly strategy (total cost US$37 893 407) and provides the similar QALY gained compared to pooled high-risk HPV testing with reflex dual stain (Average QALY 24.03). Pooled HPV test with reflex dual staining is more costly compared to strategy without reflex dual staining. The ICER was US$353.40 per QALY gained. One-way sensitivity analysis showed that the model is sensitive to the cost of dual stain and the cost of cancer treatment. Decreasing the incidence of cervical cancer case and increasing the QALYs can be successful by using dual stain cytology as the triage test for pooled HPV test or HPV genotyping. The result of our analysis favors the use of HPV genotyping with the reflex dual stain as it offers the most QALY at the lowest cost.

Human papillomavirus (HPV) is a principal driver for most oropharyngeal squamous cell carcinomas (OPSCCs), where it is strongly associated with improved survival. HPV is much less frequently detected in squamous cell carcinomas arising in nonoropharyngeal sites (non-OPSCCs), and its pathogenic role and prognostic value in these tumors is unclear. We evaluated the clinicopathologic features of 52 non-OPSCCs considered HPV-positive based upon p16 immunohistochemistry and direct HPV detection using RNA in situ hybridization (ISH), DNA ISH, or real-time DNA polymerase chain reaction. The HPV-positive non-OPSCCs were from the larynx (n = 27), oral cavity (n = 21), and hypopharynx (n = 4). While most cases (n = 34, 65%) showed classic histologic features of HPV-positive OPSCC, including endophytic growth, minimal keratinization, and hyperchromatic nuclei without koilocytic changes, a subset (n = 13, 25%) were characterized by exophytic growth, exuberant surface hyperkeratosis and parakeratosis, marked nuclear pleomorphism, and prominent koilocytic atypia. These antithetical features were highly reminiscent of the warty variant of HPV-positive squamous cell carcinoma described in anogenital sites. Compared with tumors without warty features, the warty tumors presented at lower stage and were not associated with lymph node metastasis, local recurrence, or distant spread (4 y disease-free survival of 100% vs. 66%, P = 0.069). The presence of transcriptionally active HPV as detected by RNA ISH suggests a pathogenic role for HPV in these nonoropharyngeal sites. While most HPV-positive non-OPSCCs are morphologically similar to their tonsillar counterparts, this study highlights a previously unrecognized warty variant that may be associated with a highly favorable clinical outcome.

Objective: In order to increase overall participation in cervical cancer screening, several investigators propose a concept of introducing self-tests. The study presented here compared test results of the Pap test and 4 different HPV test systems of self-collected and physician-collected vaginal specimens. Study Design: 208 patients of a colposcopy clinic had physician-taken and self-taken vaginal samples. All cell samples enabled a liquid-based Pap test and testing for carcinogenic HPV genotypes. In addition, all patients had a colposcopy with or without cervical biopsy and/or conisation. Results: 99 patients had the histological diagnosis of CIN2+. The HPV test sensitivity of self-collected samples differed significantly in this patient group depending on the test system performed. The sensitivity of the self-collected Pap test was significantly lower than HPV testing, but the positive predictive value of the Pap self-test was very high. Conclusion: The results of this study indicate that under the circumstances of self-testing HPV test systems differ in test sensitivity and specificity. Self-collected Pap tests can provide a test result with a very high positive predictive value and introduce therapeutic strategies. In order to improve screening strategies, it could be an opportunity to combine HPV and Pap tests in self-taken vaginal samples, especially in countries with a low income level. In countries with a good medical infrastructure, self-testing has to be introduced with caution.

Introduction: A causal link between infection with a high-risk strain of human papilloma virus (hrHPV) and the development of cervical squamous cell carcinoma (SCC) is well established. However, a small number of SCCs are hrHPV-negative by either HPV co-DNA testing and/or HPV-in situ hybridization (HPV-ISH) at the time of diagnosis. These apparently hrHPV-negative lesions are poorly understood, specifically whether hrHPV-positive precursor lesions exist, which would be detected through hrHPV-based screening. Methods: A search of the pathology archives at the Johns Hopkins Hospital identified women with a diagnosis of hrHPV-negative cervical SCC on surgical specimen. All prior pathologies, including cervical cytology and surgical pathology specimens, and associated hrHPV DNA test results, p16 immunohistochemistry, and HPV-ISH were reviewed. Results: A total of 25 women were identified having a surgical specimen diagnosed as SCC with either negative or equivocal HPV-ISH. Fifteen had a Pap test in the 6 months preceding a diagnosis of SCC, with cytology diagnoses as follows: high-grade squamous intraepithelial lesion n = 14/15; atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion n = 1/15. hrHPV co-testing was performed for 5 of these 15 women and was negative in 2/5 cases. Cervical biopsy was performed for 24 women. HPV-ISH testing, performed on 14 of the biopsy specimens, was negative for 11/14 patients. Of 15 specimens stained for p16, 14 were positive. Conclusion: A subset of patients exist in whom hrHPV is not detectable at or near the time of progression to SCC. Additional research is necessary to further describe this population and determine whether maintaining cytological screening would provide benefit.

Context: Infection with oncogenic or high-risk human papillomavirus (hrHPV) types acts as carcinogens in the development of cervical cancer. Aim: The aim of the study was to detect the genotypes of some hrHPVs among women attending selected hospitals in Kaduna State, Nigeria. Settings and Design: Hospital-based and cross-sectional that involved the use of structured questionnaires to obtain sociodemographic and clinical data. Materials and Methods: Two hundred and seventy-six cervical scraping samples were screened for both HPV and squamous intraepithelial lesion (SIL) using enzyme-linked immunosorbent assay and conventional Pap smear, respectively. Samples positive for HPV antigen and SIL were subjected to polymerase chain reaction (PCR) to detect the viral type. Statistical Analysis Used: Data were analyzed using the frequency procedure of Statistical Analysis System version 9.2, at 0.05 level of significance and 95% confidence interval. Results: Of the 276 cervical scraping samples, only 24 (8.7%) were positive for HPV antigen, whereas 17 (6.2%) were positive for SIL. When thirty of these positive samples were subjected to PCR, the DNA of hrHPV was detected in 20 (66.6%) of the positive samples. The HPV types detected in the study were 16 (36.7%), 18 (40.0%), 31 (16.7%), and 45 (3.3%). Conclusion: The findings from this study have shown that there is a high possibility of detecting the DNA of hrHPV in women that are infected with HPV and those that have cervical dysplasia, which points out the possibility of these women developing cervical cancer.

Background: AgNOR pleomorphism has been widely used for its diagnostic importance in differentiating premalignant and malignant lesions of different human neoplasms. However, an evaluation of its potential for discriminating cases of high-risk squamous intraepithelial lesions of the cervix (SIL) has been rarely attempted. Aim: The tumor marker potential of AgNOR pleomorphism counts was assessed by correlating high and low mean counts in low-grade SIL (LSIL) cases with persistence or regression of the lesion and HPV positivity. Materials and Methods: The 115 LSIL cases selected for the study were registered from the ongoing cervical cancer screening of the rural population of Lucknow West. Silver nitrate staining for AgNOR counts and HPV DNA testing were done in all 115 cases. Results: The AgNOR counts in the 115 LSIL cases revealed low counts in 92 and high counts in 23 cases. Follow-up, available in 107 cases, revealed persistence of the lesion in 21 of the 23 cases with high counts and in 4 of the 84 cases with low counts. HPV positivity showed a strong correlation with high counts. Persistence of LSIL was also more frequent with high AgNOR counts and in HPV-positive cases. Conclusions: The study showed a correlation of high mean AgNOR counts with HPV positivity and persistence of LSIL.

Objective: The exfoliative cell analyzer, LC-1000 (Sysmex Corporation, Japan), is a medical device that presents the cell proliferation index and 23 research parameters as indicators of cellular proliferative potential. The objective was to evaluate the clinical usability of qualitative assessment by LC-1000 compared with cytology, the human papillomavirus (HPV) test, and histology as gold standard. Study Design: Women that visited 3 sites between July 2015 and March 2017 were registered. The primary endpoint in this study was the comparison between LC-1000 measurement and HPV test for sensitivity and specificity for cervical intraepithelial neoplasia 2+ (CIN2+). A tree model algorithm was newly constructed by a statistical method and its relationship with histological results was evaluated. Results: The sensitivity and specificity of LC-1000 were 78.3 and 74.1%, while those of the HPV test were 94.7 and 85.4%, respectively. A tree model comprising five categories was constructed. The proportion of advanced lesions was higher with the change in the rank classification results from 1 to 5. The positive predictive values of CIN2+ in the categories 4 and 5 were high. Despite the small number of subjects, cancer was undetected in categories 1 and 2. In addition, the comparison with follow-up results in 19 women assessed as CIN1 showed that the rate of progression in the categories 3–5 was 50% (7/14); progression in the categories 1 and 2 was 0% (0/5). Conclusions: LC-1000 may be useful for cervical cancer screening as an index to qualitatively evaluate CIN and cancer based on the changes in characteristics of cells.

Background: Uterine cervical cancer is the fourth most common female cancer in the world. In Japan, we have an apparently low rate of joining cervical cancer screening programs compared with Western countries. Furthermore, the incidence and mortality rate of cervical cancer among the younger generation has been increasing. Object: The aim of this study was to assess the effectiveness of cervical cancer screening with human papillomavirus (HPV) testing and cytology in Japan. Methods: Collaborating with Saga City government, we initiated a cervical cancer screening system consisting of HPV testing and baseline cervical cytology from April 2011 as a social experiment. A total of 17,284 participants have been screened with this new combination system. Results: After HPV testing with cytology-based cervical cancer screening, the number of screenings done in women aged under 40 years has significantly increased. In addition, the number of women diagnosed with cervical intraepithelial neoplasia grade 3 has increased (25 of 14,025 vs. 146 of 23,049 under 50 years: p < 0.001). Conclusion: These data suggested that the introduction of HPV testing with cytology-based cervical cancer screening as an adjunct to conventional cytology resulted in better efficiency and more accurate screening among the Japanese population.

Cervical cancer is a significant public health problem, especially in low- and middle-income countries, where women have little access to cervical cancer screening; consequently 80% of cervical cancer related mortality occurs in these regions. The development of screening methods that need less infrastructure thus represents an urgent medical need. The study aims to compare the detection rates of high-risk human papillomavirus 16 and 18 E6 oncoprotein in urine, vaginal self-collected, and cervical scrapes of women using the OncoE6™ Cervical Test and compare the HPV16 and/or HPV18 E6 detection rates with the HPV DNA testing. Paired urine, vaginal self-collected and cervical specimens were collected from 124 women who participated in cervical cancer screening or treatment in this proof-of-concept study and underwent to HPV16/18-E6 testing and high-risk HPV DNA testing prior to treatment of cervical neoplasia or cancer. Concordance between urinary, vaginal and cervical HPV16/18-E6 and HPV-DNA testing was evaluated for patients classified as negative group (

Introduction: The majority of squamous cell carcinoma (SCC) of the oropharynx, one of the sites within the head and neck region, is now associated with high-risk human papillomavirus (HPV) in North America. Several modalities are available to determine the HPV status, however, the understanding of each assay in its application and limitations is essential for accurate interpretation and appropriate utilization of results in management of these patients. Areas covered: This expert review will cover the role of HPV in head and neck squamous cell carcinoma (HNSCC), indications for HPV testing, HPV detection methods in tumors, saliva and serum, and exploiting HPV status as a prognostic biomarker of clinical outcome in HNSCC. Expert commentary: The HPV status is the most significant diagnostic and prognostic biomarker in HNSCC, specifically in the oropharynx. Research underway is currently delineating the role of HPV and p16 testing in non-oropharyngeal sites. While the feasibility of non-invasive serum and saliva testing for HPV detection has been established, the clinical application of these assays is still evolving.

To describe the methods of a study aimed at evaluating high risk-HPV (hrHPV)-based screening and cervical cytology as triage compared to conventional cervical cytology as primary screening in the detection of grade 2+ cervical intraepithelial neoplasia in the National Cancer Screening Program (NCSP) of Mexico.We will use information originated from the Womens Cancer Information System of Mexico regarding cervical cancer from 2008 to 2018. The database includes cytology results, diagnostic confirmation by histopathology and/or treatment colposcopy. We will then carry out statistical analyses on approximately 15 million hrHPV.We will evaluate the overall performance of hrHPV-based screening as part of the NCSP and compare hrHPV-based to cytology-based screening under real-life conditions. To guarantee an unbiased comparison between hrHPV with cytology triage and conventional cytology we will use propensity score matching.ytology we will use propensity score matching. Conclusion. Decision makers may use our results to identify areas of opportunity for improvement in NCSP processe.Describir los métodos de un estudio que busca comparar el beneficio de la introducción de la prueba de VPH de alto riesgo como prueba primaria frente a la citología convencional para la detección de la neoplasia intraepitelial cervical grado 2 o mayor, dentro del Programa de Prevención y Control del Cáncer de la Mujer, para el periodo de 2008 a 2018.Se utilizarán los registros del Sistema de Información de Cáncer de la Mujer, se realizarán los análisis estadísticos con aproximadamente 15 millones de resultados de VPH-alto riesgo, además se utilizarán los resultados de citología, colposcopia, histología y los casos referenciados al centro oncológico para tratamiento. Para comparar ambos grupos usaremos “propensity score matching”.Se evaluará el desempeño general de la prueba de VPH-alto riesgo, en condiciones reales dentro del Programa Nacional de Prevención y Control de la Mujer y su tendencia en el tiempo.Los resultados de estudio ayudarán a los tomadores de decisiones a identificar áreas de oportunidad para mejorar el programa en México.

Objectives: Kosovo’s current health care system does not support organized nationwide cervical cancer screening and human papillomavirus (HPV) vaccination programs. To date, no reliable data are available on cervical cancer incidence and mortality in Kosovo, or on high-risk HPV (HR-HPV) prevalence and HPV type distribution. Our aim is to determinate the pre-vaccination prevalence and distribution of HR-HPVs and to assesses the associations between sociodemographic characteristics and increased risk of HPV infection in women from Kosovo. Material and methods: Detection of HR-HPV DNA in cytologically evaluated cervical smears was performed using a clinically validated Abbott RealTime High Risk HPV test, Roche Linear Array HPV Genotyping Test, HPV52 type-specific real-time PCR and an in-house GP5+/GP6+/68 PCR. Results: The crude overall prevalence of any of the HR-HPVs was estimated at 13.1% (26/199; 95% confidence interval (CI): 9.1–18.5%), with HPV16 being the most common type (7/26, 26.9%), followed by HPV31 and HPV51, each detected in 4/26 (15.4%) cervical specimens, HPV18, detected in 3/26 (11.5%) specimens, HPV52 and HPV66, each detected in 2/26 (7.7%) specimens, and HPV33, HPV45, HPV56, and HPV58, each detected in a single (3.9%) specimen. Women over 40 (OR = 0.36), older than 18 at sexual debut (odds ratio (OR) = 0.28), those that had delivered at least one child (OR = 0.32), and those that had a history of pregnancy termination (OR = 0.39) were at lower risk for HPV infection. Conclusion: Because more than 70% of cervical precancerous lesions could have been prevented in Kosovo using nationwide HPV-based cervical cancer screening and HPV vaccination, it is of outmost importance to implement both programs in the national health care system as soon as possible.