Positive High-risk Human Papillomavirus Research Articles

Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study

BackgroundThe high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30–50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue.MethodsWe collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC.ResultsThe multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 − 15 %- versus 6 out of 60 − 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 − 10 %- versus 4 out of 60 − 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity.ConclusionsOur findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %.Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.

Iranian women\u2019s psychological responses to positive HPV test result: a qualitative study

BackgroundHuman papillomavirus testing as an established screenings test allow for the early detection and treatment of cervical cancer. Testing positive for HPV may have adverse consequences for women. This study aimed to explore the psychological impacts of testing positive for HPV on women in a developing country with a distinct cultural and religious background.MethodsQualitative face-to-face semi-structured interviews were conducted with 40 Iranian women who received a positive high-risk HPV result. Content analysis approach was used to data analysis through MAXQDA10.ResultsThree main categories were emerged: initial confrontation; STD-related psychological burden; and rebuilding health. Initial reactions to positive HPV results were shock, unrealistic fear, confusion, distress, and financial concerns. Stigma was manifested in form of self-blame, fear of HPV-disclosure, negative body image, being stigmatized by healthcare providers, and receiving health care anonymously. Refusal to use insurance services showed how evident and powerful the stigma was. Most women reported lifestyles and sexual behaviors modifications to help their immune system to clear HPV; indicating that the screening can work as a valuable opportunity to improve women's physical and sexual health. Regular follow-up, safe sex and a focus on spirituality enable women infected with HPV to take control of the situation. Worrying about other HPV-linked cancers (oropharynx and anal) and fears of partner infection indicated that women consider HPV to be more than just a cause of cervical cancer.ConclusionsThe findings implied to the HPV-positive women's need to support and factual information. Designing and implementing interventions that mitigate the psychological effect of positive HPV test results can highlight the potential benefits of screening for women's health.

Human Papillomavirus Oral- and Sero- Positivity in Fanconi Anemia.

Simple SummaryPeople with Fanconi anemia (FA) are genetically susceptible to gynecological cancers and cancers of the head and neck. There are known associations between oral infection with human papillomavirus (HPV) and development of head and neck cancers. This study sought to measure how common oral HPV positivity is in a large sample of people with FA followed over 8 years, while also evaluating serum titers to ascertain natural exposure to HPV, and how well people with FA who were vaccinated responded to HPV vaccination. We found that oral HPV positivity is significantly higher in individuals with FA compared to family and unrelated controls, but that response to HPV vaccination between FA and controls is similar. Common risk factors associated with HPV in the general population did not predict oral DNA positivity in FA, unlike unrelated controls. Future mechanistic and vaccinations studies are needed to understand this phenomenon.High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predisposition to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken. Oral DNA samples from 201 individuals with FA, 303 unaffected family members, and 107 unrelated controls were tested for 37 HPV types. Serum samples from 115 individuals with FA and 55 unrelated controls were tested for antibodies against 9 HPV types. Oral HPV prevalence was higher for individuals with FA (20%) versus their parents (13%; p = 0.07), siblings (8%, p = 0.01), and unrelated controls (6%, p ≤ 0.001). A FA diagnosis increased HPV positivity 4.84-fold (95% CI: 1.96–11.93) in adjusted models compared to unrelated controls. Common risk factors associated with HPV in the general population did not predict oral positivity in FA, unlike unrelated controls. Seropositivity and anti-HPV titers did not significantly differ in FA versus unrelated controls regardless of HPV vaccination status. We conclude that individuals with FA are uniquely susceptible to oral HPV independent of conventional risk factors.

High-Risk Human Papillomavirus Testing, Genotyping, and Histopathologic Follow-up in Women With Abnormal Glandular Cells on Papanicolaou Tests.

This study examined the association of high-risk human papillomavirus (hrHPV) status and HPV genotype with histopathologic follow-ups in women with an atypical glandular cell (AGC) interpretation. Cases with AGC interpretation on a Papanicolaou (Pap) test were retrieved along with hrHPV testing, genotyping, and histologic follow-up results if available. A total of 561 AGC cases were identified, with histologic follow-up available for 471 cases (84%). The follow-up diagnoses included benign or reactive changes (60% of cases), low-grade cervical intraepithelial neoplasia (18%), high-grade cervical intraepithelial neoplasia (CIN2-3; 7%), cervical carcinoma (5%), and other malignancies (10%). Tests for hrHPV were positive in 128 of 426 (30%) cases, including HPV16 (30%), HPV18 (14%) and other HPV subtypes (56%). A positive hrHPV result significantly increased the risk of developing CIN2-3 or cervical carcinoma (odds ratio, 24.6; 95% CI, 9.9-58.9) and HPV16 or HPV18 further increased the risk (odds ratio, 49.5; 95% CI, 17.7-123.7). Our data demonstrate that in women with an AGC Pap interpretation, a positive hrHPV result, especially type 16 or 18, is associated with an increased risk of developing cervical CIN2-3 or higher lesions, suggesting potential implications of hrHPV testing for the management of patients with an AGC result on a Pap test.

Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results: Incidence and Characterization in a Large, Contemporary United States Cohort.

Early studies estimate that 5% to 10% of oropharyngeal squamous cell carcinomas overexpress p16 but are unassociated with transcriptionally-active high-risk human papillomavirus (HPV). Patients with discordant HPV testing may experience clinical outcomes that differ from traditional expectations. To document the rate of p16 and HPV mRNA positivity, characterize patients with discordant testing, and identify features that may warrant selective use of HPV-specific testing after p16 IHC, a multi-institutional, retrospective review of oropharyngeal squamous cell carcinoma patients with p16 IHC and HPV mRNA testing by reverse transcriptase polymerase chain reaction was performed. Of the 467 patients, most had T1 or T2 tumors (71%), 82% were p16 positive, and 84% were HPV mRNA positive. Overall, most tumors were nonkeratinizing (378, 81%), which was strongly associated with p16 and HPV positivity (93% and 95%, respectively). Overall, 81% of patients were double positive, 14% double negative, and 4.9% discordant (3.4% p16 negative/HPV mRNA positive and 1.5% p16 positive/HPV mRNA negative). The survival rates of these discordant patient groups fell squarely between the 2 concordant groups, although in multivariate analysis for both disease-free survival and overall survival, discordant patients were not found to have statistically significantly different outcomes. Reclassifying patients by applying HPV mRNA testing when p16 results and morphology do not match, or when p16 results are equivocal, improved prognostication slightly over p16 or HPV mRNA testing alone. Patients with discordant testing demonstrate a borderline significant trend toward survival differences from those with concordant tests. When evaluated independently, patients who were p16 negative but HPV mRNA positive had a prognosis somewhat closer to double-positive patients, while those who were p16 positive, but HPV mRNA negative had a prognosis closer to that of double-negative patients. We suggest an algorithm whereby confirmatory HPV mRNA testing is performed in patients where p16 status is not consistent with tumor morphology. This captures a majority of discordant patients and improves, albeitmodestly, the prognostication.

Self-sampling for high-risk human papillomavirus as a follow-up alternative after treatment of high-grade cervical intraepithelial neoplasia.

Women treated for high-grade cervical-intraepithelial-neoplasia (CIN) require long-term follow-up with high-risk human-papillomavirus (HPV) testing. Self-sampling for HPV is well-accepted among these patients, but its role in follow-up for this group requires investigation. The present study examined how well HPV findings from self-sampled vaginal (VSS) and urine specimens correctly identified women from this cohort with recurrent CIN2+ compared with samples collected by clinicians. At 1st post-conization follow-up, 531 patients (99.8% participation) gave urine samples, performed VSS, underwent colposcopy with punch biopsy of visible lesions and clinician-collected cervical sampling for HPV analysis and liquid-based cytology. A total of 113 patients with positive HPV and/or abnormal cytology at 1st follow-up underwent 2nd follow-up. At 1st follow-up, all patients with recurrent CIN3 had positive HPV results by all methods. Clinician sampling and VSS revealed HPV16 positivity in 50% of recurrent cases and urine sampling revealed HPV16 positivity in 25% of recurrent cases. At 2nd follow-up, all 7 newly-detected CIN2/3 recurrences were associated with HPV positivity on VSS and clinician-samples. Only clinician-collected samples detected HPV positivity for two adenocarcinoma-in-situ recurrences, and both were HPV18 positive. A total of 77 patients had abnormal cytology at 1st follow-up, for which HPV positivity via VSS yielded highest sensitivity. The HPV findings were positive from VSS in 12 patients with high-grade squamous-intraepithelial-lesions (HSIL), and 11 patients with HSIL had positive HPV findings in clinician-collected and urine samples. All methods for assessing HPV presence yielded significant age-adjusted odds ratios for predicting abnormal lesions at 1st follow-up. For overall HPV results, Cohen's kappa revealed substantial agreement between VSS and clinician sampling, and moderate agreement between urine and clinician sampling. Clinician sampling and VSS were highly concordant for HPV16. Insofar as the pathology was squamous (not glandular), VSS appeared as sensitive as clinician sampling for HPV in predicting outcome among the present cohort. Since VSS can be performed at home, this option can maximize participation in the required long-term follow-up for these women at high-risk.

Current status of cervical cytology during pregnancy in Japan

In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology during pregnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy.

Relation of Human Papilloma Virus Infection with Pre Malignant and Malignant Endometrial Lesions

Endometrial carcinoma is the second most common gynecologic cancer worldwide. Hyperplasia is aprecursor to endometrioid adenocarcinoma. There are few studies on the association of HPV with endometrialadenocarcinoma.Aim of the Study: To determine the relation of HPV with premalignant and malignant endometrial lesions.Patients and Method: This study achieved on a total number of 90 patients with histopathologicalexamination revealing endometrial hyperplasia in 30 patient, endometrial carcinoma in 30 patient in additionto 30 cases who underwent hystrectomy, for all patients detection of HR-HPV done by RT-PCR.Results: The HR-HPV positivity was recorded in 23 patients. For the studied cases with endometrialcarcinoma, endometrial hyperplasia and controls the positivity rates were about (16.7%), (36.7%) and(23.3%) respectively. Highest rate of HR-HPV positivity for the studied patients was found in the age group(45-49). Highest rate of HR-HPV positivity in cases with endometrial carcinoma was reported in older agegroups [(45-49) and (50-54)], compared to endometrial hyperplasia and controls [(40-44) and (45-49)]. TheHR-HPV positivity was most frequently observed in cases with well-differentiated (22.2%). Higher HRHPV positivity rate was reported in the hyperplasia without atypia.Conclusion: No role of HR-HPV in the pathogenesis of endometrial carcinoma.

Comparison of colposcopic biopsy results of cervical cytology-negative and HPV 16/18 or other high-risk HPV subtypes

Aim: This study aimed to compare the colposcopic biopsy results of patients with negative cervical cytology and positive human papillomavirus (HPV) tests and to investigate the necessity of colposcopy in patients with cytology-negative/other high-risk HPV (non-HPV 16/18) positive results. Materials and Methods: The study included 126 patients aged 30–65 years who underwent HPV DNA testing between 2016 and 2019 and who underwent colposcopic biopsy at our hospital because of their positive results. The patients were divided into three groups: HPV16/18 positivity, other high-risk HPV positivity, and unclassified HPV positivity. Cytology and colposcopy-guided cervical biopsy results were compared with the HPV types. Results: Approximately 44.4% of the patients had HPV 16/18 positivity, 23% had other high-risk HPV positivity, and 32.5% had unclassified HPV positivity. The cytology results revealed that 57.1% of patients were negative for intraepithelial lesions or malignancy (NILM), 22.2% had atypical squamous cells of undetermined significance, 17.5% had low-grade squamous intraepithelial lesions (LGSIL), and 2.4% had high-grade squamous intraepithelial lesions. Colposcopic biopsy results were normal in 15.1% of the patients, showed LGSIL in 15.9%, high-grade squamous intraepithelial lesions (HGSIL) in 10.3%, and cervical cancer in 0.8% of the patients. Evaluation of the biopsy results based on HPV type in the patients with NILM cytology revealed that 12.8% of those with HPV 16/18 positivity had LGSIL and 17.9% had HGSIL, whereas 7.1% of those with other high-risk HPV positivity had HGSIL and 7.1% had LGSIL. Conclusions: The possibility of detecting dysplasia in the colposcopic biopsies of patients who are NILM and HPV 16/18-positive is higher than in the colposcopic biopsies of patients with other high-risk HPV types; therefore, these patients should be evaluated using colposcopic biopsy. Colposcopic biopsy is unnecessary in the presence of NILM and other high-risk HPV types.

Use of extended HR-HPV Genotyping in improving the Triage Strategy of 2019 ASCCP recommendations in Women with positive HR-HPV diagnosis and Simultaneous LSIL Cytology Results.

Objective: According to the 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) recommendations, women with a positive high-risk human papillomavirus (HR-HPV) diagnosis and low-grade cervical intraepithelial lesion (LSIL) cytology result should be referred for further colposcopy examination. However, this strategy results in over-treatment in several cases. In this study, we assessed the performance of extended HR-HPV genotyping in women with a simultaneous positive HR-HPV and LSIL diagnosis with the aim of improving the current triage strategy.Methods: This study was an observational analysis of women from the Fujian Province Cervical Lesion Screening Cohorts (FCLSCs). Women who were HR-HPV-positive and had a cytological examination of LSIL, which were followed up with colposcopy and biopsy, from 2015 to 2018 were included. The study endpoint was defined as the detection of histological cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We combined HR-HPV genotypes according to the prevalence rate in histological CIN2+ and ranked them from high to low to establish HR-HPV genotyping models. Outcomes were assessed with respect to sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and colposcopy referral rate.Results: Overall, 56,788 women undergoing preliminary screening for HR-HPV genotyping were included in this study. Among them, 10,499 women positive for HR-HPV underwent a cytology examination, and 902 women with LSIL cytology diagnosed and subsequent biopsy results were included in the final evaluation. Among these patients, 25.1% (226/902) were found to have CIN2+ in histology. HPV-16, -58, -52, -18, -33, and -31 infections were the most common genotypes, and HPV-16, -18, -58, -33, and -31 (odds ratio [OR] = 5.41, 2.98, 1.38, 1.24, and 1.21, respectively) were associated with the potential for histological CIN2+, from the highest to lowest. In the detection of CIN2+ lesions in HR-HPV-positive LSIL women of different HR-HPV genotyping models, the extended HPV 16/18/31/33/52/58 genotyping model was found to have better efficacy with higher sensitivity (92.9%) and NPV (93.0%), but a significantly lower colposcopy referral rate (74.7%) than the ASCCP-recommended HR-HPV non-genotyping model.Conclusion: For HR-HPV-positive women with LSIL, the HPV 16/18/31/33/52/58 genotyping model can serve as an alternative approach to the ASCCP recommendations, potentially reducing the unnecessary colposcopy referral burden in China.

Brush Samples of Oral Lesions to FTA Elute Card for High-risk Human Papilloma Virus Diagnosis.

To investigate the level of agreement between three non-invasive methods for hrHPV diagnosis in oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC) and in oral mucosal lesions. For hrHPV DNA FTA Elute card™ and Anyplex II HPV28™ were used and for hrHPV mRNA PreTect SEE™ in tumour patients (n=60), non-tumour lesions (n=51), immunosuppression or previous hrHPV-infection (n=32). The level of agreement between the DNA-methods was 82.2% (k=0.54, p=0.001). Pair-wise comparison for the FTA Elute card were close to the reference (AUC=0.83, 95% CI=0.73-0.90). hrHPV mRNA was diagnosed in 50% of the tumours, with an agreement level of 58.3%, compared to Anyplex II (k=0.17, p=0.04). The hrHPV positivity in oral lesions was 3.9% for immunosuppression and for previous HPV infection 9.4%. The FTA card is reliable for hrHPV DNA diagnosis while mRNA gives an insight into viral activity and correlates with severity of the lesion.

Validation of CINtec® PLUS Cytology Kit in the Diagnosis of Persistent HPV Infections - Cohort Study in the Portuguese Population.

Context:The use of the CINtec® PLUS Cytology Kit as a complementary method of diagnosis is intended to contribute to a risk assessment of CIN II+ cervical lesions development, thus avoiding unnecessary colposcopy in negative cases. This method has proved to be effective in the follow-up of cervical lesions, although there is need for consistency in the approach of equivocal or negative cytological results, with persistent positive High-Risk Human Papillomavirus (HR-HPV) test.Aims:The present study intends to retrospectively evaluate the capacity of the CINtec® to add information to the clinical practice within the screening and follow-up of cervical lesions. Additionally, this study intends to define criteria for CINtec® referral in order to maximize its utilization in the Portuguese context.Materials and Methods:For this purpose, 225 cases with CINtec® PLUS Cytology Kit and histology results were used, and data were analysed and compared according to the cytology and HR-HPV molecular test results.Results:The data of this study show that CINtec® PLUS Cytology Kit is a valid test for the diagnosis of persistent HPV lesions (p = 0.0005), with excellent sensitivity and reliable values of specificity. Relevant patient groups to apply the kit are in agreement with the manufacturer recommendations: women with ASC-US/LSIL result and NILM cytology with HPV-positive test, essentially over 30 years old.Conclusions:Although clinical data and previous cytological information must help guiding, authors considered that CINtec® is a really valid test for the prognosis of persistent HPV infections in the female population.

DNA ploidy measurement and human papillomavirus in abnormal cervical cytology.

To compare the efficacy of high-risk human papillomavirus (HR-HPV) and DNA image cytometry (DNA-ICM) status for identifying high-grade cervical intraepithelial neoplasia or worse (≥CIN2). This cross-sectional study was performed in women undergoing follow-up procedure after a previous abnormal cervical cytology. Cervical cells were collected for HPV detection and DNA ploidy measurement. Biopsy samples were taken for histological confirmation. Sensitivity and specificity values for ≥CIN2 detection with HR-HPV and DNA-ICM were determined. HR-HPV was present in 74.5% of the women. The most frequent HPV infection was HPV 16, followed by HPV 31, 33 and 58. Aneuploidy was observed in 60.6% of all cases. Referral cytology revealed 78.0% sensitivity and 68.6% specificity for detecting a≥CIN2 lesion. The HR-HPV test alone showed 92.7% sensitivity, albeit it was not statistically different from DNA-ICM (88.1%, P>.05). Positivity for HPV or DNA-ICM resulted in 100% sensitivity. Higher specificity was observed for the combination of HR-HPV and DNA-ICM (88.6%), with no difference from DNA-ICM alone (85.7%, P>.05). DNA-ICM or HR-HPV positivity identified all cases of≥CIN2 in women undergoing follow-up procedure after a previous abnormal cervical cytology. Routine cervical cancer screening could be improved by the incorporation of DNA-ICM as a complementary method to primary screening to identify which women need closer follow-up.

Diagnostic performance of immediate colposcopy among women with high-risk human papillomavirus (HPV) other than HPV 16/18 and normal cytology.

Persistent infection with 1 of 14 high-risk genotypes human papillomavirus (HPV) genotypes is the crucial for the development of high-grade cervical cancer precursors. The reassuring management of women with cytology negative, high-risk HPV (HrHPV) positive is important especially after the widespread use of HPV testing either as a cotest. The aim of our study was to compare the colposcopic biopsy results of women with HPV 16/18 with other Hr-HPV genotypes and determine positive predictive values (PPV) for CIN2+ of other HR HPV genotypes. We prospectively had included the women with negative cytology and positive Hr-HPV test other than HPV 16/18. Control group was composed of women with negative cytology positive test results for either HPV 16 or HPV 18. Women with HrHPV positive, cytology negative referred to immediate colposcopy. The prevalence of CIN1 and CIN2 is significantly higher in HPV 16/18 group than pooled other HrHPV group (34.1% vs 17.5%, P = 0.01 for CIN 1+; 14.8% vs 5.2%, P = 0.03 for CIN 2+). The prevalence of CIN3 was almost three fold in women with HPV 16/18 (9.1% vs 3.1%). PPV for CIN 2+ was 16.4 (9.1-27.3) for HPV 16, 11.7 (2-37.7) for HPV 18, 20 (3.5-55.7) for HPV 31, 11.1 (0.6-49.3) for HPV 51, 12.5 (0.6-53.3) for HPV 58 and 59. We showed the relative high PPV for CIN2+ in OHrHPV other than HPV 16/18 positive group among cytology negative population. HPV 33, 51, 58, 59 and 18 had similar PPV for CIN2+ in basal cytology negative population.

Follow-up Findings in Postconservative Treatment Surveillance for Women With Cervical Adenocarcinoma In Situ

The risks of adenocarcinoma in situ (AIS) recurrence or progression after conservative treatment are uncertain. The aim of this study was to examine the role of high-risk human papillomavirus (hrHPV) and cytology in the posttreatment surveillance of AIS patients. Follow-up results of hrHPV status, cytology results, and clinicopathological features of 207 patients were retrospectively analyzed, in whom AIS was initially treated by loop electrosurgical excision procedure (LEEP)/cone biopsy between September 2009 and June 2018. Among 207 patients diagnosed AIS on LEEP/cone biopsy, 30.9% (64/207) had positive margins. Persistent/recurrent AIS rate was substantially higher in the patients with positive margins than in those with negative margins (47.2% vs 9.3%, p < .001). Of 74 patients with hrHPV surveillance, 17 (17/74, 23.0%) were found to have positive hrHPV and 4 (4/17, 23.5%) had the persistent/recurrent AIS regardless of margin status. On the contrast, no AIS were found in negative surveillant hrHPV patients (23.5% vs 0%, p < .001). Lastly, 27.8% patients (22/79) were reported atypical glandular cells on surveillant cytology, and 9 persistent/recurrent AIS cases were further identified on second biopsy or hysterectomy with a positive detection rate of 40.9%. In this study, we concluded the positive margin on LEEP/cone biopsy in AIS patients was associated with a significantly greater risk of disease persistence or recurrence. The posttreatment surveillance by cytology and adjunct hrHPV would be an ideal strategy in predicting AIS persistence and recurrence, which will warrant further treatments.

Urine collection in cervical cancer screening \u2013 analytical comparison of two HPV DNA assays

BackgroundTo reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women’s acceptance of urine collection and preferences towards the different sampling procedures.MethodsOne hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference.ResultsWith the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure.ConclusionsUrine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.

Acceptability of self- collection for human papillomavirus detection in the Eastern Cape, South Africa.

Human papillomavirus (HPV) testing on vaginal self-collected and cervical clinician-collected specimens shows comparable performance. Self-sampling on FTA cards is suitable for women residing in rural settings or not attending regular screening and increases participation rate in the cervical cancer screening programme. We aimed to investigate and compare high-risk (HR)-HPV prevalence in clinician-collected and self-collected genital specimens as well as two different HPV tests on the clinician collected samples. A total of 737 women were recruited from two sites, a community health clinic (n = 413) and a referral clinic (n = 324) in the Eastern Cape Province. Cervical clinician-collected (FTA cards and Digene transport medium) and vaginal self-collected specimens were tested for HR-HPV using the hpVIR assay (FTA cards) and Hybrid Capture-2 (Digene transport medium). There was no significant difference in HR-HPV positivity between clinician-collected and self-collected specimens among women from the community-based clinic (26.4% vs 27.9%, p = 0.601) or the referral clinic (83.6% vs 79.9%, p = 0.222). HPV16, HPV35, and HPV33/52/58 group were the most frequently detected genotypes at both study sites. Self-sampling for HPV testing received a high positive response of acceptance (77.2% in the community-based clinic and 83.0% in referral clinic). The overall agreement between hpVIR assay and HC-2 was 87.7% (k = 0.754). The study found good agreement between clinician-collected and self-collected genital specimens. Self-collection can have a positive impact on a cervical screening program in South Africa by increasing coverage of women in rural areas, in particular those unable to visit the clinics and women attending clinics where cytology-based programs are not functioning effectively.

Cervical human papillomavirus prevalence, risk factors and outcomes in a cohort of HIV-infected women in Harare, Zimbabwe.

BackgroundHuman papillomavirus (HPV) associated invasive cervical cancer (ICC) is common in Zimbabwe, disproportionately affecting women living with HIV (WLHIV). Understanding high-risk HPV (hrHPV) infection in relation to cervical disease is important for ICC prevention amongst WLHIV.ObjectivesTo describe the prevalence of cervical hrHPV, type distribution, associated risk factors and ICC screening outcomes in an urban cohort of Zimbabwean women.MethodsIn this cohort study, WLHIV were tested for hrHPV infection using the Cepheid Xpert® HPV assay and followed up for incident cervical disease. Follow-up assessments were done by visual inspection with acetic acid (VIA). Descriptive statistics and logistic regression were used to describe hrHPV burden and association between hrHPV and potential risk factors. Incidence rates (IR) and rate ratios of cervical disease by hrHPV infection status were also calculated.ResultsAmongst 321 WLHIV recruited, hrHPV prevalence was 24.9% (n = 80). Fifty-two of these women (65%) were positive for hrHPV types other than 16 or 18/45. Younger age (22–29 years), early sexual debut (13–16 years) and antiretroviral therapy (ART) regimen (second-line ART) were independently associated with hrHPV positivity. Positive VIA IR ratio between hrHPV-positive and -negative women was 12.57 (95% confidence interval [CI]: 4.14–38.19). Only women with hrHPV infection had incident cervical disease (IR: 6.41/100 person-years, (95% CI: 3.33–12.32). There were no ICC cases by the end of the 2-year follow-up.ConclusionThere was a high prevalence of hrHPV infection other than 16 and 18/45 in this cohort. Integrating HPV testing in cervical cancer screening programmes may increase screening intervals in hrHPV-negative women, reducing costs for programmes. We recommend further research into cross protectivity of the bivalent and quadrivalent HPV vaccines against these other hrHPV types.

HPV co-testing as cervical screening test, Experience of Alweiya early detection cervical clinic: one-year Analysis

Objectives: The high-risk Human papilloma virus test with conventional cytology (HPVco-test) was firstly introduced in our institute at May 2019 so we aimed to estimate the prevalence of abnormal cytology and positive high-risk human papillomavirus test results in a screening woman and to assess the accuracy between cytology and Human papilloma virus testing to evaluate the feasibility of integrating the latter as a primary test in the national cervical cancer screening program.&#x0D; Methods: A prospective study for women attending to early detection cervical clinic, during the period from May 2019 to May 2020. Patients who were sexually active were included in the study. Samples for conventional cytology and HPV by using real-time polymerase chain reaction technique for high risk types were taken concurrently. The prevalence of positive screening results and the difference in accuracy between two testing were estimated by McNemar’s χ2 test.&#x0D; Result: A total of 388 women were included in the study. The prevalence of positive test for hr-HPV was 2.1%(8) while the prevalence of abnormal cytology test was 19.1%(74), Concerning discordant pairs, 0.8%(3) of women had normal cytology with a positive hr-HPV test result and 17.8%(69) of women had abnormal cytology with a negative hr-HPV test result. A total of 311 (80.1%) women had normal cytology and negative hr-HPV test results. The proportion of women with abnormal cytology and positive hr-HPV test results was 1.3% (5 women). the difference in accuracy between the two results was statistically significant (&lt;0.0001). The prevalence of positive hr-HPV test decreased with increasing age, whereas the prevalence of abnormal cytology showed a bimodal age pattern.&#x0D; Conclusion: The prevalence of abnormal cytology was high to that of hr-HPV testing, which could not allow for the implementation of hr-HPV as a primary test in the national screening program in Iraq.

Primary HPV screening for cervical cancer: Results after two screening rounds in a regional screening program in Finland.

Since 2012, cervical cancer screening has been conducted with a primary high-risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high-grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test. The primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low-grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV-positive women with a negative or equivocal cytology triage were re-screened after approximately 12-16months. hrHPV-negative women were scheduled for re-screening after 5years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35-55years old in 2012, and 40-60years old in 2017. In all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35- to 55-year age cohort. In 2017, 4807 (73%) of the women aged 40-60years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P=.002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P=.220). In the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test.