High-risk Human Papillomavirus Testing Research Articles

Dual Switch in Lipid Metabolism in Cervical Epithelial Cells during Dysplasia Development Observed Using Raman Microscopy and Molecular Methods.

Simple SummaryRaman microscopy is an inexpensive and label-free method. The literature describes many attempts to use this method for cancer diagnosis. In this study, we used it to differentiate the lipid profile of cervical epithelial cells depending on the severity of pathological changes and the presence of HPVhr infection. Using molecular methods, we also determined the degree of methylation of the gene encoding the prolipidogenic protein SREBP1, as well as the number of copies of the mitochondrial genome in the tested samples. This multimethodological approach allowed not only to determine the differences between samples with different advancement of pathological changes, but also enabled to shed light on the molecular mechanism behind them, as well as gave hope for the possibility of using our approach for early detection of cervical dysplasia in the future.Cellular lipid metabolism is significantly transformed during oncogenesis. To assess how dysplasia development influences lipid cellular metabolisms and what is the molecular background behind it, cervical epithelial cells of 63 patients assigned to seven groups (based on the cytological examination and HPVhr test results) were studied using a multimethodological approach including Raman microscopy and molecular methods. The consistent picture obtained studying the lipid content, cell inflammation, SREBF1 gene methylation (hence SREBP1 inhibition) and level of mitochondrial DNA copies (indirectly the number of mitochondria) showed that changes in lipid metabolism were multidirectional. Cells from patients classified as mildly dysplastic (LSIL) exhibited a unique behavior (the highest level of inflammation and SREBF1 methylation, the lowest lipid content and mitochondrial DNA). On the contrary, cells from severe dysplastic (HSIL) and cancer (SCC) groups showed the opposite characteristics including the lowest SREBF1 gene methylation as well as the highest level of mitochondrial DNA and lipid cellular concentration (for HSIL/HPVhr+ and SCC groups). Following dysplastic progression, the lipid content decreases significantly (compared to the control) for mildly abnormal cells, but then increases for HSIL/HPVhr+ and SCC groups. This intriguing dual switch in lipid metabolism (reflected also in other studied parameters) on the way from normal to squamous carcinoma cells is of potential diagnostic interest.

Anal cytology and high-risk human papilloma virus testing in atypical squamous categories: Value of concurrent testing in management of high-risk population.

Anal squamous cell carcinoma is relatively rare, but its incidence and mortality have been increasing worldwide. While anal cytology is a sensitive cancer screening modality, its specificity is low, and data for concurrent high-risk human papilloma virus (HR-HPV) testing are limited. At our institution, anal cancer screening consists of combined anal cytology and high-risk human papilloma virus (HR-HPV) testing on all specimens. The aims of the study were to correlate results of atypical cytological diagnoses [atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)] with HR-HPV testing and determine if co-testing may potentially influence management. A retrospective search over 24-months was performed for anal cytology specimens with diagnoses of ASCUS and ASC-H. Corresponding HR-HPV (HPV 16/18 and Other-31/33/35/39/45/51/52/56/58/59/66/68) results were retrieved, and concordance/discordance was recorded. Cytology results were correlated with anal biopsy diagnoses, when available. A total of 139 patients, including 127 with ASCUS and 12 with ASC-H, were identified. Of the ASCUS cases, 90/127 (70.9%) had HR-HPV, and a squamous intraepithelial lesion (SIL) was evident in 20/39 (51.2%) of biopsies. All 12/12 (100%) ASC-H were associated with HR-HPV and 3/6 (50%) biopsies had a SIL. Our study supports use of concurrent cytology and HR-HPV for anal cancer screening cytology. Co-testing improves specificity of atypical cytology diagnoses and can identify patients requiring further intervention.

Cervical Cancer Screening in Postmenopausal Women: Is It Time to Move Toward Primary High-Risk Human Papillomavirus Screening?

Background: Cervical cytology in postmenopausal women is challenging due to physiologic changes of the hypoestrogenic state. Misinterpretation of an atrophic smear as atypical squamous cells of uncertain significance (ASCUS) is one of the most common errors. We hypothesize that high-risk human papillomavirus (hrHPV) testing may be more accurate with fewer false positive results than co-testing of hrHPV and cervical cytology for predicting clinically significant cervical dysplasia in postmenopausal women. Materials and Methods: We conducted a retrospective analysis of 924 postmenopausal and 543 premenopausal women with cervical Pap smears and hrHPV testing. Index Pap smear diagnoses (ASCUS or greater vs. negative for intraepithelial lesion) and hrHPV testing results were compared with documented 5-year clinical outcomes to evaluate sensitivity and specificity of hrHPV compared with co-testing. Proportions of demographic factors were compared between postmenopausal women who demonstrated hrHPV clearance versus persistence. Results: The prevalence of hrHPV in premenopausal and postmenopausal women was 41.6% and 11.5%, respectively. The specificity of hrHPV testing (89.6% [87.4-91.5]) was significantly greater compared with co-testing (67.4% [64.2-70.4]) (p < 0.05). A greater proportion of women with persistent hrHPV developed cervical intraepithelial lesion 2 or greater (CIN2+) compared with women who cleared hrHPV (p = 0.012). No risk factors for hrHPV persistence in postmenopausal women were identified. Conclusion: Our data suggest that hrHPV testing may be more accurate than co-testing in postmenopausal women and that cytology does not add clinical value in this population. CIN2+ was more common among women with persistent hrHPV than those who cleared hrHPV, but no risk factors for persistence were identified in this study.

Evaluation of high-risk human papillomavirus testing and anal cytology to detect high-grade anal intraepithelial neoplasia

Optimal screening for detection of anal precancer has not been established, and most studies involve very high-risk populations. We evaluated high-risk human papillomavirus (HPV) testing and anal cytology to detect high-grade anal intraepithelial neoplasia (≥AIN2) in a cohort with mostly moderate risk factors for AIN. Patients ≥35 years old undergoing anal biopsy for various lesions received HPV testing by Roche cobas and a subset by Hologic APTIMA HPV assays with concurrent anal ThinPrep cytology. Biopsies were blindly reviewed by 3 authors, and consensus diagnosis was compared with HPV and cytology results. Sensitivity and specificity for ≥AIN2 detection by HPV testing and cytology (≥ASC-US) were calculated. Among 64 patients, 19 (29.7%) showed ≥AIN2 on biopsy. All patients were tested by cobas, and 35 (54.7%) were positive. A subset of 39 patients were also tested by APTIMA, and 18 (46.2%) were positive. Positive cytology (≥ASC-US) was present in 37 (57.8%) patients, with 27 (73.0%) of these positive by cobas. HPV testing alone yielded 75.0% and 84.2% sensitivity for APTIMA and cobas, respectively; specificity was 66.7% and 57.8%. Sensitivity and specificity of cytology alone was 78.9% and 51.1%. Combined HPV testing and cytology had a sensitivity and specificity of 91.7% and 37.0% for APTIMA and 94.7% and 40.0% for cobas. Combined HPV testing and cytology had the highest sensitivity for ≥AIN2 detection, with a performance comparable to cervical cancer screening tests, suggesting this strategy may represent a viable screening option in a population with moderate risk factors for AIN.

T Cell Receptor Repertoires Acquired via Routine Pap Testing May Help Refine Cervical Cancer and Precancer Risk Estimates.

Cervical cancer is the fourth most common cancer and fourth leading cause of cancer death among women worldwide. In low Human Development Index settings, it ranks second. Screening and surveillance involve the cytology-based Papanicolaou (Pap) test and testing for high-risk human papillomavirus (hrHPV). The Pap test has low sensitivity to detect precursor lesions, while a single hrHPV test cannot distinguish a persistent infection from one that the immune system will naturally clear. Furthermore, among women who are hrHPV-positive and progress to high-grade cervical lesions, testing cannot identify the ~20% who would progress to cancer if not treated. Thus, reliable detection and treatment of cancers and precancers requires routine screening followed by frequent surveillance among those with past abnormal or positive results. The consequence is overtreatment, with its associated risks and complications, in screened populations and an increased risk of cancer in under-screened populations. Methods to improve cervical cancer risk assessment, particularly assays to predict regression of precursor lesions or clearance of hrHPV infection, would benefit both populations. Here we show that women who have lower risk results on follow-up testing relative to index testing have evidence of enhanced T cell clonal expansion in the index cervical cytology sample compared to women who persist with higher risk results from index to follow-up. We further show that a machine learning classifier based on the index sample T cells predicts this transition to lower risk with 95% accuracy (19/20) by leave-one-out cross-validation. Using T cell receptor deep sequencing and machine learning, we identified a biophysicochemical motif in the complementarity-determining region 3 of T cell receptor β chains whose presence predicts this transition. While these results must still be tested on an independent cohort in a prospective study, they suggest that this approach could improve cervical cancer screening by helping distinguish women likely to spontaneously regress from those at elevated risk of progression to cancer. The advancement of such a strategy could reduce surveillance frequency and overtreatment in screened populations and improve the delivery of screening to under-screened populations.

Characteristics and Related Factors of High-Risk Human Papillomavirus Infection in Pregnant Women.

BackgroundCervical cancer is a risk for women worldwide. The aim of this study was to examine the occurrence of high-risk human papillomavirus (HR-HPV) infection and its related factors in pregnant women and provide a scientific basis for the targeted prevention and treatment of cervical cancer in pregnant women.Material/MethodsA total of 1774 pregnant women were included, and 1774 non-pregnant women were selected as controls. Cervical exfoliated cells were collected from all women for HR-HPV (AptimaE6, E7mRNA) and ThinPrep cytologic testing, and the vaginal discharge of all pregnant women was tested for pH level and routine pathogenic microorganisms.ResultsThe HPV-16-positive and HPV-16/18/45-positive rates in pregnant women were higher than those of non-pregnant women (P<0.05). There was a statistically significant difference in HR-HPV-positive rate, HPV-16-positive rate, and non-HPV-16/18/45-positive rate among pregnant women of different ages (P<0.05). There was a statistically significant difference in HR-HPV-positive rate and non-HPV-16/18/45-positive rate in the first, second, and third trimester (P<0.05). The HR-HPV-positive rate, HPV-16-positive rate, HPV-18/45-positive rate, and non-HPV-16/18/45-positive rate of pregnant women with concurrent infection were higher than those in women without concurrent infection (P<0.05). The HR-HPV-positive and HPV-16/18/45-positive rates in pregnant women were associated with cytologic examination results (P<0.05).ConclusionsThe overall infection rates of HR-HPV-16 and HR-HPV-18/45 in pregnant women were higher than those in non-pregnant women. The gestation period was found to be a susceptible period for infection with HR-HPV, and we recommend the implementation of cervical cancer screening based on HR-HPV testing in pregnant women.

High-risk human papillomavirus testing in women with ASCUS cytology: results from The ATHENA HPV study

This study evaluated the clinical performance of the cobas 4800 HPV Test (Roche Molecular Systems, Pleasanton, CA, USA) for high-risk human papillomavirus (HR-HPV) testing with individual HPV-16/HPV-18 genotyping in women 21 years or older with atypical squamous cells of undetermined significance (ASCUS). Women (N = 47,208) were recruited in the United States during routine screening, and liquid-based cytology and HPV testing were performed. The ASCUS prevalence was 4.1% (1,923/47,208), and 1,578 women underwent colposcopy with valid results. The cobas 4800 HPV Test demonstrated performance comparable to the Hybrid Capture 2 test (QIAGEN, Gaithersburg, MD, USA) for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse and grade 3 or worse. HPV-16/HPV-18+ women had a greater absolute risk of CIN 2 or worse compared with pooled HR-HPV+ and HR-HPV- women (24.4%, 14.0%, and 0.8%, respectively).The cobas 4800 HPV Test is clinically validated for ASCUS triage. HPV-16/HPV-18 genotyping can identify women at highest risk for high-grade cervical disease, and this additional risk stratification may be used in formulating patient management decisions.

Promotion of Cervical Screening among Long-term Non-attendees by Human Papillomavirus Self-sampling.

Cervical cancer is preventable through gynecological screening. To promote participation among non-attending women, self-collected vaginal samples for detection of high-risk human papillomavirus (hr-HPV) is an option. The aims of this study were to investigate the response of self-collected vaginal samples for hr-HPV testing among long-term non-attendees, to explore the attendance at follow-up among HPV-positive women, and to analyze the prevalence of hr-HPV and severe cervical dysplasia or cancer among the responders. A vaginal self-sampling kit was sent to 19,766 women aged 30-70 years who had not provided a cervical screening sample for ≥ 7 years in Skåne, Sweden. The self-sample was analyzed by the Aptima HPV mRNA assay (Hologic). Women testing positive for HPV were invited for follow-up. The response was 18.5% (3,646/19,757). The prevalence of HPV mRNA was 11.3% (412/3,636). Among HPV-positive women, 85.7% (353/412) attended follow-up, and of these, 44.8% (158/353) had HPV in the cervical sample. The HPV mRNA test of self-samples showed a positive predictive value of 9.3% ([33/353], 95% CI = 6.5-12.9) for detection of cytologically severe dysplasia. Histologically severe dysplasia or cancer was detected in 0.88% ([32/3,636], 95% CI = 0.6-1.2) among responders, including two cervical- and one vaginal cancer. In conclusion, almost one fifth of the long-term non-attendees participated in self-collected vaginal hr-HPV sampling. The prevalence of histologically confirmed high grade squamous intraepithelial lesion or cervical cancer was not increased significantly compared to regularly screened women in Sweden. The relatively high HPV prevalence among the self-samples indicates the importance of diagnostic follow-up with cervical HPV testing and reflex-cytology of HPV-positive cases.

Cost Savings of HPV Testing Alone Versus Co-Testing for Cervical Cancer Screening at a Student-Run Free Clinic

Background: Primary high-risk human papillomavirus (hrHPV) testing is an approved alternative method of cervical cancer screening by the United States Preventative Services Task Force. The University of South Florida BRIDGE (Building Relationships and Initiatives Dedicated to Gaining Equality) Clinic is a student-run free clinic with limited screening resources, serving patients below the poverty line. This study aimed to determine the potential cost benefit of primary hrHPV testing in this population.&#x0D; Methods: A retrospective observational study of clinic invoices and patient charts from January 2014 to December 2018 of women receiving cervical cancer screening by co-testing was performed. &#x0D; Results: BRIDGE spent $29,122.37 on screening over the five-year period for 128 patients. By elimi-nating cervical cytology, the clinic would have saved $11,594.34. Fifteen patients had abnormal results, ten of which were hrHPV-positive.&#x0D; Conclusions: The $11,594 saved would allow BRIDGE to screen 110 more patients by primary hrHPV testing and another three by eliminating follow-up for atypical squamous cells of undetermined significance, hrHPV-negative results. One patient with low-grade squamous intraepithelial lesion and negative hrHPV represents a 0.8% risk of missing precancerous lesions the clinic would assume by adopting primary hrHPV testing.

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.

Major Risk Factors for Cervical Cancer in Northeast of Iran: Evidence from a Case-Control Study

Background: Cervical cancer is a preventable cancer with various risk factors. In this study, we assessed different risk factors involved in invasive cervical cancer in the Northeast of Iran. Methods: In a case-control study, 99 patients with advanced cervical cancer were compared to 102 healthy, normal women. Cervical cancer risk factors were documented for these groups using a questionnaire and available medical notes. Univariate analysis was done for each risk factor, followed by multivariate regression analysis, to evaluate the most powerful risk factors after adjustment. Results: Multivariate model indicated that sexual transmitted diseases (STD) [p&lt;0.001; OR=7.88, 95% CI (2.59-23.93)], age at first intercourse ≤16 [p=0.048; OR=6.22, 95% CI (1.06-36.51)] and age [p=0.001; OR= 1.11, 95% CI (1.04-1.18)] were independently significant risk factors for cervical cancer. Conclusion: According to this survey, the significant influence of major risk factors, including STD, age at first intercourse, and age itself, has been underlined. Moreover, increasing the social knowledge and educating people to prevent highrisk sexual behaviors, HPV testing, and routine use of HPV vaccine, which is nowadays regarded as a preventive measure in cervical cancer, may also be needed to be implemented in our prevention program.

Clinical performance and acceptability of self-collected vaginal and urine samples compared with clinician-taken cervical samples for HPV testing among women referred for colposcopy. A cross-sectional study

ObjectivesTo increase effectiveness of the cervical cancer screening program, self-sampling can be an option. Both self-collected vaginal samples (SCV) and urine samples may be useful alternatives to clinician-taken cervical samples...

Detection of Cervical Lesions and Cancer in Air-Dried Cytologic Smears by Combined Analysis of mRNA and miRNA Expression Levels

Cervical cancer screening is based on cytologic analysis and high-risk human papillomavirus (HR-HPV) testing, each having their drawbacks. Implementation of new biomarker-based methods may improve screening accuracy. Here, the levels of 25 microRNAs (miRNAs, miRs) and 12 mRNAs involved in cervical carcinogenesis in 327 air-dried Papanicolaou-stained cervical smears from patients with cervical precancerous lesions, cancer, or without the disease were estimated by real-time PCR. Using logistic regression analysis, small-scale miRNA-based, mRNA-based, and combined molecular classifiers were built based on paired ratios of miRNA or mRNA concentrations; their ability to detect high-grade cervical lesions and cancer was then compared. Combined mRNA-miRNA classifiers manifested a better combination of sensitivity and specificity than miRNA- and mRNA-based classifiers. The best classifier, combining miR-375, miR-20, miR-96, CDKN2A, TSP4, and ECM1, predicted high-grade lesions with diagnostic sensitivity of 89.0%, specificity of 84.2%, and a receiver-operating characteristic area under the curve of 0.913. Additionally, in a subsample of the same specimens, the levels of MIR124-2 and MAL promoter methylation, HR-HPV genotypes, and viral loads were analyzed. The relative high-grade lesion risk estimated by the classifier correlated with the frequency of MAL and MIR124-2 methylation but not with the HR-HPV genotype or viral load. The results support the feasibility of cellular biomarker-based methods for cervical screening and patient management.

Would Women With Solid Organ Transplant Qualify for Triennial Cervical Cancer Screening as Recommended by the American College of Obstetricians and Gynecologists in 2016 and American Society for Colposcopy and Cervical Pathology in 2019?

The aim of the study was to assess the applicability and safety of cervical cancer screening guidelines recommended by the American College of Obstetricians and Gynecologists (2016) and American Society for Colposcopy and Cervical Pathology (2019) for women with solid organ transplants (SOTs). We analyzed data previously abstracted through December 2015 for 971 women (18-60 y) who received their first SOT at Mayo Clinic (Rochester, MN) from January 17, 1995, through December 31, 2011. Inclusion criteria were initial benign findings on cervical cytology after SOT and at least 1 subsequent cytologic screening. Of 415 women whose initial cytologic findings were benign, 310 met inclusion criteria. The cumulative incidence of abnormal cervical cytology among these 310 women was 4.3% (95% CI = 1.9%-6.7%) by 30 months and 11.2% (95% CI = 7.1%-15.4%) by 60 months after their initial benign results. Considering all women with SOT, 68.4% (284/415) had no documented abnormal cytologic findings within 60 months (26 had abnormality; 284 no abnormality; and 105 not assessed). In women with negative tests for human papillomavirus, high-grade squamous intraepithelial lesions were not documented on cytology with variable duration of follow-up. No cervical squamous cell carcinoma was identified. Of women with initial benign cervical cytology after SOT, more than two thirds would have been eligible for extended-interval screening. Further study is needed, particularly regarding the role of high-risk human papillomavirus testing.

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.

HPV types, cervical high-grade lesions and risk factors for oncogenic human papillomavirus infection among 3416 Tanzanian women

ObjectiveThe objective of the present study was to assess the prevalence and type-specific distribution of cervical high-risk (HR) human papillomavirus (HPV) among women with normal and abnormal cytology, and to...

Comparing Anal Cancer Screening Algorithms Using Cytology and Human Papillomavirus DNA Testing in 3 High-Risk Populations.

Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36). Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.

Raising Funds Through Social Media to Subsidise Cervical Cancer Screening with HPV Testing in Rural Ghana-The Battor Experience.

Over 260,000 women die yearly from cervical cancer, mostly in low and middle-income countries. Molecular testing for high-risk Human Papilloma Virus (HPV) is now the method of choice for cervical cancer screening. A limiting factor for HPV testing, however, is the cost in setting up and running the tests. Our objective was to reduce the cost of cervical cancer screening to rural folk by absorbing the initial cost of setting up. Crowdfunding was done through WhatsApp© and mobile money transfer. Individuals pledged amounts ranging from United States of America dollars ($) 2.6 to $3,769.2 (median = $25.6, Inter Quartile Range (IQR) = $12.8 to $38.5). Over four months $15,153 was raised to purchase the initial equipment for an HPV-based cervical cancer screening program. Crowdfunding is possible through a combination of WhatsApp© and mobile money transfer in low-resource settings. It obviates the need to organize gatherings requiring a budget and enables donors to become fundraisers.

Revisiting the Cost-Effectiveness of HPV Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening

Objectives: Consensus U.S. cervical cancer screening guidelines recommend women aged 30–65 years should be screened: (1) every 5 years with high-risk HPV testing alone; or (2) every 5 years with Pap and high-risk HPV co-testing; or (3) every 3 years with Pap alone. However, nearly 1-in-5 cancers (18.6%) are missed by HPV testing alone and 12.2% of cancers are missed by Pap testing alone. Hence, co-testing is the preferred screening method, but the cost implications are not fully known. For deeper understanding, we performed updated clinical-economic comparisons of cervical cancer screening with co-testing versus primary HPV from a U.S. perspective. Methods: A health state transition (Markov) model with one-year cycling was previously developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. After updating the model, it was used to perform simulations of women receiving either 3-year or 5-year interval cervical cancer screening with either co-testing or HPV primary, starting from age 30 years and running up through age 64 years. Outcomes included total and incremental differences in costs, number of referral colposcopies (true and false positive), invasive cervical cancer (ICC) cases, ICC deaths, and quality-adjusted life years (QALYs) for cost-effectiveness calculations. Results: In the 3-year and 5-year screening interval scenarios, per-patient cumulative costs of screening and management over 35 years with co-testing versus HPV primary led to cost savings of $15 and $217, respectively. These cost saving resulted from fewer referral colposcopies, fewer ICC cases, and fewer ICC deaths. Co-testing also conferred more QALYs. Cost-effectiveness calculations showed co-testing as the economically dominant screening strategy by simultan-eously confers greater effectiveness (i.e., more QALYs) at lower cost compared with HPV primary. National average annual cost savings of $154 to $655 million could be realized if every woman in the U.S. was routinely screened with co-testing instead of HPV primary. Conclusions: Model results demonstrate that cervical cancer screening with co-testing provides valuable clinical and economic outcomes when compared to primary HPV testing alone. These findings are relevant to healthcare payers and women’s health policy advocates seeking cost-effective cervical cancer screening options.