Positive High-risk Human Papillomavirus Test Research Articles

Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions.

To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. To investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed. A total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05). In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Self- and physician-collected high-risk human papillomavirus (HPV) testing to detect high-grade cervical lesions among Thai women

ObjectiveWe compared the performance of high-risk human papillomavirus (HPV) messenger RNA testing of physician- and self-collected specimens for detecting histological grade 2 or higher cervical intraepithelial neoplasia (CIN) among women...

Histopathologic Follow-Up of Women with Inadequate ThinPrep™ Cervical Pap Tests and Positive High-Risk Human Papillomavirus Test Results

Introduction: We found only a few studies that had performed high-risk human papillomavirus (hrHPV) analyses of inadequate ThinPrep™ Papanicolaou (Pap) tests. Therefore, this study aimed to analyze unsatisfactory ThinPrep Pap tests using hrHPV tests. The colposcopic biopsy results of cases with an unsatisfactory ThinPrep Pap test and positive hrHPV results were revealed. Methods: Between January 1, 2018, and October 31, 2022, 965 (3.7%) of 25,958 liquid-based cytology specimens were evaluated as unsatisfactory. Ninety-five (9.8%) of 965 patients were positive for hrHPV. The colposcopic evaluation was performed in 28 (29.4%) of 95 patients, in whom 23 tests were adequate. Results: Twenty-three colposcopy biopsy results showed that 17 (73.9%) of 23 patients had benign biopsy results. High-grade squamous intraepithelial lesions were observed in three (13%) of the 23 patients, and low-grade squamous intraepithelial lesions were observed in two (8.6%) of the 23 patients. One of the 23 (4.3%) patients had keratinized squamous cell carcinoma of the cervix diagnosed histologically, although no tumor was visible upon gynecologic examination. Conclusion: For the management of unsatisfactory Pap tests, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends repeat cytology within 2–4 months. Evaluation of such patients using hrHPV tests may triage those with squamous intraepithelial lesions, even invasive cervical cancer. More studies with a larger number of cases are needed to analyze the hrHPV status and biopsy follow-up of cases with unsatisfactory cytology.

Screening Tests and Support in Positive Human Papilloma Virus Tests

Screening for the detection of Cervical Cancer (CC) is moving from cytology or Papanicolaou (Pap) test to the detection of the primary highrisk Human Papillomavirus (HPV) test, based on evidence for this change, with support or triage options for positive HPV test results with better access innovations. The test of higher specificity such as cytology makes it an option for triage in positive HPV tests; but cytology and genotyping have been recommended for all positive HPV tests, especially for the other pool-positive hr-HPVs; but HPV-16/18 negative. Screening with primary HPV testing has been shown to be effective, affordable, and acceptable to women, especially in emerging countries; the use of Dual Staining (DS) to classify positive HPV results has higher sensitivity and specificity than HPV-16/18 genotyping or cytology at triage.

Prevalence of cervical high-risk human papillomavirus and cytological abnormalities in elderly Turkish women

Objective: Cervical cancer (CC) screening ends at the age of 65 in Turkey, as in many countries. However, about a quarter of CCs occurs in women over the age of 65. Persistent high-risk human papillomavirus(HR-HPV) infection is the most important factor leading to CC. In this study, we aimed to investigate the prevalence of cervical HR-HPV and cytological abnormalities in Turkish women aged 65 and over. Patients and Methods: A total of 467 women between the ages of 66-84 who were referred to the gynecology outpatient clinics for any reason between January 2010 and December 2021 were included in the study. Pap smears (liquid-based) of patients were screened for HPV DNA typing using the COBAS test system and evaluated cytopathologicaly. Results: The mean age of women was 72.4 years. The prevalence of HR – HPV was 5.1% (n = 24), HPV-16 and HPV-18 subtypes constituted 58.4% of all positive cases. The rate of cervical HR-HPV and cytological abnormalities were not statistically different between age groups. Of the women with a positive HR-HPV test in Pap smear, cytological abnormalities were found to be more frequent when compared to HR-HPV negatives (95.8%, n=23 vs 4.3%, n=19, p&amp;lt;0.00001). Conclusion: We demonstrated a strong correlation between HR-HPV positivity and cytological abnormality in the elderly women population. Age groups were not significantly different regarding the prevalence of HR-HPV and abnormal cytology. We also revealed that the prevalence of HR-HPV and cytological abnormalities in the elderly population were not high enough to explain the second peak of cervical cancer seen in older ages. More studies are needed to explain which testing methods should be used in the elderly patient population.

Superficial spreading cervical squamous cell carcinoma in situ involving the endometrium: a case report and review of the literature

BackgroundThe spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer.Case presentationWe present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months’ duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery.ConclusionsSquamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease.

Prevalence of abnormal Pap smear results in inflammatory bowel disease: a prospective study.

Development of malignancy is a pending threat for patients with inflammatory bowel disease (IBD). Aim of this study was to analyze cervical dysplasia and infection with human papilloma virus (HPV) in patients with IBD. This was a prospective, single center cohort study in Germany. Consecutive IBD patients admitted to the Department of Gastroenterology were sent to Gynecology, where a questionnaire was answered and gynecological examinations including a smear for cytology and HPV were taken. Participants of a general screening program constituted controls. Descriptive statistics, 95% confidence intervals and odds ratios were calculated. A total of 101 patients were recruited of which 99 patients participated. Analysis showed a significant (p = 0.05) difference between the prevalence of abnormal smears in patients with (22%) and without (6%) immunosuppressive therapy, while the latter had cervical abnormalities comparable with healthy controls (5%). All immunosuppressants showed similarly high risks for abnormal smear results. Only 11/99 (11%) patients had positive high-risk HPV tests, which is comparable with general population. The prevalence of abnormal cervical smears is higher in IBD patients compared to healthy individuals, but the difference is confined to patients with IBD and immunosuppressive therapy. Annual screening is advisable.

Acceleration of cervical cancer diagnosis with human papillomavirus testing below age 30: Observational study.

Several international cervical screening guidelines advise against using high-risk human papillomavirus (HR-HPV) testing in women younger than 30. The rationale for this in young women, lies in the potential for additional detection of both low-grade and high-grade cervical intraepithelial neoplasia (CIN) leading to unnecessary treatments without reducing the burden of cervical cancer. We studied 56 544 women screened at 24 to 29 with HR-HPV testing and 116 858 screened with liquid-based cytology (LBC) in the English HPV screening pilot. They were compared to 528 460 women screened at the age of 30 to 49. We studied the detection of cervical cancer and CIN2/3 across two consecutive screening rounds 3 years apart. At 24 to 29, a positive HR-HPV test detected more cases of cervical cancer in the prevalence round than did a positive LBC test (1.36/1000 screened vs 0.82/1000, ORadj : 1.61, 95% CI: 1.18-2.19). In women with a negative HR-HPV test, cervical cancer was diagnosed before or at the incidence round in 0.07/1000. After a negative LBC test, cancer detection reached 0.47/1000 and 40% of these cases were diagnosed at FIGO stage IB+. HR-HPV testing increased the detection of CIN2/3 diagnoses in two consecutive rounds combined by 30% (71.9/1000 vs 55.2/1000). The patterns of detection of cervical cancer and CIN2/3 were almost identical at older ages. These data support using HR-HPV testing for screening of women younger than 30, which not only accelerates the diagnosis of cervical cancer but leads to a similar relative increase in CIN2/3 diagnosis to that found in women aged 30 to 49.

Cervical Cancer Screening in South Florida Veteran Population, 2014 to 2020: Cytology and High-Risk Human Papillomavirus Correlation and Epidemiology.

ObjectiveThis project aims to use our robust women's health patient data to analyze the correlation between cytology and high-risk human papillomavirus (Hr-HPV) testing, study the performance of Hr-HPV testing for detecting cytology lesions, and examine epidemiologic measures of human papillomavirus (HPV) infections in the women's veteran population.MethodsWe collected patient data from 2014 to 2020 from our computerized patient record system. We performed HPV assays using the cobas® 4800 system (Roche Diagnostics, Basel, Switzerland). The cobas HPV assay detects HPV 16, HPV 18, and 12 other HPV types (31, 33, 35, 39, 45, 51, 56, 58, 59, 66, and 68). We organized cytology results and Hr-HPV assays with Microsoft Access and Microsoft Excel (Microsoft Corporation, Washington, USA) for analysis.ResultsA total of 9437 cervical specimens were co-tested. High-grade cytology lesions - high-grade intraepithelial lesion (HSIL) or higher and atypical squamous cells, cannot exclude HSIL (ASC-H) - were overwhelmingly positive for Hr-HPV (94.1% and 87.2%, respectively). Low-grade cytology lesions - low-grade squamous intraepithelial lesion ((LSIL) and atypical squamous cells of undetermined significance (ASC-US) - were positive for Hr-HPV in lower percentages (72.6% and 54.9%, respectively). Hr-HPV testing had a sensitivity of 91.3%, a specificity of 93.1%, a positive predictive value of 16.4%, and a negative predictive value of 99.8% for detecting high-grade cytology lesions. Hr-HPV testing had a lower performance for detecting low-grade cytology lesions. Ten cases had high-grade cytology and negative Hr-HPV test. Out of 10 such patients, nine showed no dysplasia (six) or low-grade dysplasia (three) on subsequent biopsy. Overall, 14.4% of tests were positive for Hr-HPV. The highest positive Hr-HPV test rates were in the third and eighth decades of life, 25.1% and 22.0%, respectively. However, the eighth decade consisted of a small sample of only 50 women. In women over 30 years of age with Hr-HPV infections, HPV types 16 and 18 were present in 11.7% and 6.4% of tests, respectively. Other HPV types were present in 82.3% of tests.ConclusionsHr-HPV testing has a high performance in detecting high-grade cytology lesions and a lower performance for detecting low-grade cytology lesions. However, studies show that LSIL rarely progresses to cervical intraepithelial neoplasia grade 3 or higher (CIN3+), suggesting minimal to no impact on cervical cancer screening. We believe our findings are in accordance with recent studies and affirm the guidelines that recommend primary Hr-HPV testing as the preferred screening method. The percentage of positive Hr-HPV tests and rates for age and HPV types 16 and 18 in our women’s veteran population suggest similar HPV prevalence to that of the general US population.

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.

MOLECULAR MARKERS FOR THE DIAGNOSIS OF HIGH-RISK HUMAN PAPILLOMAVIRUS INFECTION AND TRIAGE OF HUMAN PAPILLOMAVIRUS-POSITIVE WOMEN.

Infection with high-risk human papillomavirus (HPV) increases the likelihood of developing cervical cancer (CC). A plethora of cellular processes is required to produce pre-malignant lesions, which in turn may become malignant if left untreated. Those changes are induced by viral oncoproteins, which represent an ideal target to identify the viral presence, or by some particularities of the host that ultimately promote the establishment of CC. This article describes the different methods used for HPV detection and quantification, as well as the current trend of secondary screening approaches to detect premalignant lesions and CC. In addition, we analyzed validated biomarkers and those under clinical investigation for the classification (triage) of women at risk of developing CC after an initial positive HPV test and that could be used as prognostic biomarkers for CC. The use of molecular biomarkers, together with the detection of HPV DNA sequences, provides a high impact diagnostic and prognostic tool in the detection of patients at increased risk of developing CC and also may guide their clinical management. In addition, some of those biomarkers could represent pharmacological targets for the future design of therapeutic approaches to CC treatment.

4553 An investigation into the use of curcumin, a topical herbal agent, for the treatment of cervical intraepithelial neoplasia

4553 An investigation into the use of curcumin, a topical herbal agent, for the treatment of cervical intraepithelial neoplasia

Abstract 2421: Factors associated with abnormal cervical cancer screening results among screening compliant women in the United States

Abstract Introduction: Formal guidelines recommend routine cervical cancer screening using the Papanicolaou (Pap) test and / or screening for high risk Human Papillomavirus (HPV). This study aims to describe the factors associated with abnormal cervical cancer screening outcomes. Methods: We analyzed data from 7,716 women, aged 30 to 65 years, who were respondents of the 2015 Cancer Control Supplement (CCS) of the National Health Interview Survey (NHIS). Weighted multinomial logistic regression was used to examine the factors associated with i) abnormal Pap test, ii) positive high-risk HPV test, as well as iii) abnormal Pap and positive high-risk HPV tests. Results: Overall, 16.8% [95% CI, 15.6 to 18.0] of women who screened for cervical cancer in the last 3 years, had an abnormal result. Risk of abnormal cervical cancer screening results decreased as age increased. Compared to the younger age group (30-45 years), those aged 56-65 years had lower odds of an abnormal Pap test (aOR: 0.71, 95% CI: 0.55, 0.92), positive high-risk HPV test (aOR: 0.51, 95% CI: 0.27, 0.97) or abnormal Pap and positive high-risk HPV tests (aOR: 0.55, 95% CI: 0.35, 0.88). Similarly, women who were married or living with a partner were less likely to have an abnormal Pap test (aOR: 0.83, 95% CI: 0.69, 1.00), than unmarried women. On the contrary, geographic region, race and cigarette smoking were found increase the odds of an abnormal cervical cancer screening result. Blacks were more likely to have abnormal screening results compared to Whites. Current smokers had increased odds of abnormal Pap test (aOR: 1.33, 95% CI: 1.02, 1.73) and positive high-risk HPV test (aOR: 1.94, 95% CI: 1.13, 3.32), compared to never smokers. Discussion: Study findings call for continued surveillance of cancer screening outcomes. More so there is a need for further studies to examine factors promoting an increased likelihood of abnormal cervical cancer screening results in populations identified in this study. Note: This abstract was not presented at the meeting. Citation Format: Onyema Greg Chido-Amajuoyi, Sanjay Shete. Factors associated with abnormal cervical cancer screening results among screening compliant women in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2421.

High-risk human papillomavirus infection in female and subsequent risk of infertility: a population-based cohort study

To study whether infection with high-risk human papillomavirus (HPV), registered both as a single HPV positive test and as HPV persistence, increases the risk of female factor infertility in later reproductive life. Population-based cohort study. Not applicable. A random sample of 11,088 women (20-29years of age at enrollment) tested for cervical HPV at enrollment during 1991-93 and again after 2years. Information on female factor infertility was obtained by linkage to the Danish Infertility Cohort. None. Follow-up for each study participant was the period from the date of enrollment or date of the second visit until diagnosis of female factor infertility (main outcome), conception, death, emigration, disappearance, or end of study period. Data were analyzed by means of a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HPV status and female factor infertility after adjustment for potentially confounding factors were determined. After relevant exclusions, 10,595 women were eligible for analysis, 1,861 (17.6%) of whom were high-risk HPV positive at the first visit. There was no association between a positive HPV test at first visit (HR = 0.88; 95% CI, 0.75-1.02) or positivity for the same high-risk HPV type at the first and second visit (persistence; HR = 0.97; 95% CI, 0.66-1.44) and subsequent risk of female factor infertility in reproductive life. We found no association between a high-risk HPV infection and risk of female factor infertility, neither for a single HPV positive test nor for a persistent HPV infection.

Management of Atypical Squamous Cell Cases: A Prospective Study of Women seen at a Private Health Service in Northeastern Brazil.

To assess the management chosen by gynecologists after atypical squamous cells (ASCs) cytology results, and to evaluate the outcomes of these cases in Brazilian women. A prospective observational study evaluated the initial management offered by the gynecologist in the case of 2,458 ASCs cytology results collected between January of 2010 and July of 2016. The outcomes of the cytology, high-risk human papilloma virus (HR-HPV) test and histology were compared in two subgroups: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H). In many cases of ASC-US (36.97%) and ASC-H (40.50%), no clinical actions were taken. Cytology was the most frequent follow-up chosen, including for cases of ASC-H, which goes against the conduct recommended in the national guideline. In women over 30 years of age, the period of time elapsed between an ASC-US result and a new cytology was in 13.03 months, in disagreement with the national guideline recommendations (p < 0.0001). Negative for intraepithelial lesions or malignancy (NILM) cytologic (p = 0.0026) and histologic (p = 0.0017) results in the follow-up were associated with prior ASC-US, while negative results for ASC-H were cytologically (p < 0.0001) and histologically associated with high-grade squamous intraepithelial lesion (HSIL) (p < 0.0001). Two invasive cervical carcinomas (ICCs) were found in the follow-up for ASC-H, and there was a statistically significant association (p = 0.0341). A positive HR-HPV test was associated with ASC-H (p = 0.0075). The data suggest that even for a population of Brazilian women assisted at private clinics, the national guidelines recommendations for ASCs results are not followed.

Annals for Educators - 2 January 2018.

Annals for Educators - 2 January 2018.

Atypical Squamous Cells in Liquid-Based Cervical Cytology: Microbiology, Inflammatory Infiltrate, and Human Papillomavirus-DNA Testing

Objective: The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests. Study Design: A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results. Results: An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370). Conclusion: ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology.

Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3‐year follow‐up in an academic institute

Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities.

Cervical biopsy rates before and after the introduction of human papillomavirus type reporting in co-tests with negative cytology

In 2013, our laboratory introduced Roche cobas high-risk human papillomavirus (HRHPV) testing, which includes limited HPV genotype reporting. The shift from Hybrid Capture II (HC2) HPV testing to Roche led to an observed increase in biopsies for patients with negative Papanicolaou tests with positive HRHPV. We conducted a retrospective review of data from our facility to examine biopsies conducted on patients with negative Papanicolaou tests and positive HRHPV. We compared data from 2012 (HC2) to 2015 after implementation of Roche cobas platform. In 2012, 37 biopsies were performed on patients with negative Papanicolaou test and positive HRHPV, out of 82,721 Papanicolaou tests (0.045%). In 2015, the number of biopsies performed on patients with negative Papanicolaou test and positive HRHPV test was 281, out of 115,104 Papanicolaou tests (0.244%; P < 0.001). Of these, 141 had HPV type 16 or 18, and 140 had "other" HRHPV types. We observed an increased detection rate of high-grade squamous intraepithelial lesion (HSIL) or greater lesions (5.4% in 2012 to 8.9% in 2015), but it was not statistically significant (P = 0.398). Fifteen HSIL or greater lesions were found in women with types 16 or 18 (5.3%) and 10 were found in women with "other" HRHPV types (3.6%). The introduction of HRHPV testing with type reporting is associated with a marked increase in the number of women undergoing colposcopy and biopsy for HRHPV despite negative cytology. Half of these have a HRHPV type other than type 16 or 18, despite recommendations to repeat co-testing instead.

Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: split-sample study.

BackgroundHigh-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays.MethodsConsecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested with the three evaluated DNA and mRNA HPV assays. Genotyping was undertaken using CLART HPV2 assay, individually detecting 35 genotypes. The presence or absence of cervical lesions was determined with histological examinations; women with abnormal cytology were managed as per routine recommendations; those with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months.ResultsCross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3 assays. None of the 35 genotypes was detected in 49 (1.0 %), 162 (3.2 %), and 56 (1.1 %) samples, respectively. In primary screening at age 30 to 65 years (n = 2859), samples of 72 (25 %) out of 289 with high-risk infections on HC2 and < CIN2 histology were due to cross-reactivity. On cobas, this was 106 (26 %) out of 415, and on APTIMA 48 (21 %) out of 224.ConclusionsDespite manufacturer claims, all three assays showed cross-reactivity. In primary cervical screening at age ≥30 years, cross-reactivity accounted for about one quarter of false positive test results regardless of the assay. Cross-reactivity should be addressed in EU tenders, as this primarily technical shortcoming imposes additional costs on the screening programmes.