The role of human papillomavirus deoxyribonucleic acid for distinguishing between cervical adenocarcinoma and endometrial adenocarcinoma

HIGHLIGHTS1. Determining primary tumor between uterine cervical adenocarcinoma and endometrial carcinoma is often complicated due to the lack of specimen or overlapped histological and morphological spectrum.2. The distinction between endometrial and endocervical adenocarcinoma preoperatively is important because the treatment is different.3. The samples from each group are tested for HPV DNA using PCR method.4. High risk HPV infected patients have a higher probability to become uterine cervical adenocarcinoma.5. HPV DNA test has a role for distinguishing between uterine cervical adenocarcinoma and endometrial carcinoma. ABSTRACTObjectives: To analyze the role of HPV DNA for distinguishing between uterine cervical adenocarcinoma and endometrial adenocarcinoma.Materials and Methods: This was a case control study using paraffin block samples from uterine cervix adenocarcinoma and endometrial adenocarcinoma operation at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. Each group was tested for HPV DNA using PCR method. Sample size was 18 in each group.Results: A total of 36 samples fulfilled the inclusion criteria in this study. Each group comprised 18 samples. There were 83.3% of uterine cervical adenocarcinoma and 11.1% of endometrial adenocarcinoma that revealed high risk HPV. Chi-Square test result found significant correlation between high risk HPV and uterine cervical adenocarcinoma (p<0.05) with Odds Ratio (OR) 40.00 (CI 95%).Conclusion: There was a significant correlation between high risk HPV and uterine cervix adenocarcinoma. High-risk HPV infected patients had a risk to suffer from uterine cervical adenocarcinoma compared to those with endometrial adenocarcinoma. HPV DNA test had a role for distinguishing between uterine cervical adenocarcinoma and endometrial adenocarcinoma.

Self-collected versus clinician-collected cervical samples for the detection of HPV infections by 14-type DNA and 7-type mRNA tests

Background HPV self-sampling has been widely supported by the scientific community following a strong body of literature on the subject. Self-sampling is important in cervical cancer screening as it has been shown to improve participation. It is well documented that HPV-testing has proven superior to cytology with regards to sensitivity in detection of CIN and cancer. The value of self-collected samples is reliant on the quality of the molecular testing performed, as well as the patients’ preference in sampling procedure and compliance to follow up on positive test results. Due to the incompatibility of self-samples and cytology, triage of HPV-DNA positives by testing for molecular biomarkers is highly warranted. Methods Our objective was to compare the detection rate of genital Human Papillomavirus (HPV) infection in self- and clinician-collected samples by a 14-type HPV-DNA test and a 7-type mRNA E6/E7 test. Results Five hundred five women were recruited. Each study participant had two sample collection procedures performed upon the same visit, alternating order in execution of the self-collection or the clinician-taken procedure first or second, 1010 samples in total. HPV-DNA prevalence was 22.8% in self-collected versus 19.2% in clinician-collected samples (P = 0.19). Overexpression of mRNA E6/E7 from 7 HPV types was 7.1 and 6.3%, respectively (P = 0.71). The difference between HPV-DNA and HPV-mRNA positivity rates were statistically significant in both self-collected (22.8% versus 7.1%, P < 0.001) and clinician-collected samples (19.2% versus 6.3%, P < 0.001). Overall agreement between the two collection methods was fair, with a concordance rate of 78.2% (390/505), k = 0.34 (95% CI: 0.25–0.44), P < 0.001, for the HPV-DNA test and 92.5% (467/505), k = 0.40 (95% CI, 0.25–0.56), P < 0.001, for the mRNA test, respectively. 96.8% of the participants reported they felt confident carrying out the self-collection themselves, and 88.8% reported no discomfort at all performing the procedure. Conclusions This comparative study of two sampling methods reports fair agreement of HPV positivity rates between the self-collected and clinician-collected specimens using Abbott hrHPV and PreTect HPV-Proofer’7 tests. Only one third of HPV-DNA positive women had overexpression of mRNA E6/E7. Trial registration ISRCTN77337300.

The diagnostic value of HPV E6/E7 mRNA test in young women with cervical squamous intraepithelial lesion: A Retrospective Analysis

Background At present, the HPV DNA test is used to triage young female patients with abnormal cytology. Still, it is not suitable to precisely identify the population with persistent HPV infection. The purpose of this study was to evaluate the diagnostic value of HPV E6/E7 mRNA test in young women with abnormal cytology by comparing HPV DNA test.Methods A total of 258 young women aged 20 to 29 years,with squamous cell abnormalities on the cervical cytology, were enrolled in this study between January 2015 and December 2019.All patients were subject to HPV DNA test, HPV E6/E7mRNA test,colposcopy biopsy, and histopathological examination.A comparative analysis of the diagnostic performance of the HPV DNA test and HPV E6/E7mRNA test was conducted according to the histological diagnosis(CIN II and CIN II+were defined as high-grade squamous intraepithelial lesion+(HSIL+)).Results The results showed that HPV E6/E7 mRNA test had a higher specificity of 47.3%(40.0%-55.1%) for HSIL+ compared to HPV DNA test that had specificity of 16.0% (11.0%-22.6%)in young women(P<0.01). The HPV E6/E7 mRNA test presented high rates of specificity,positive predictive value (PPV), and negative predictive value(NPV), which were 92.1%(86.0%-96.0%), 62.1%(42.4%-78.7%), 92.1%(85.9%-95.8%), respectively, compared to that of HPV DNA,which were 15.8%(10.4%-23.2%),14.6%(9.40%-21.9%), and 71.0%(51.8%-85.1%),respectively(P<0.01)in young women with mildly abnormal cytology(ASC-US and LSIL). Yet, with severe abnormal cytology(ASC-H and HSIL), HR-HPV test was similar to HPV E6/E7 mRNA test in sensitivity(χ2=0.98,P=0.322),specificity(χ2=0.938,P=0.333),PPV(χ2=0.074,P=0.786) and NPV(χ2=0.00,P=1.000).Conclusions Compared to the HPV DNA test,the HPV E6 /E7mRNA test has better clinical value in screening cervical cancer and predicting the risk of HSIL+ in young women, especially those with mild abnormal cytology.

The outcome of colposcopy in women attending with persistent postcoital bleeding and negative HPV-DNA test

Objective: Women with postcoital bleeding (PCB) are recommended to be evaluated by colposcopy even if cytology is negative. Human papillomavirus (HPV) testing increases the detection of cervical intraepithelial neoplasia or worse compared to the Pap smear test. We aimed to determine the incidence of cervical pathology among women with persistent PCB with a negative Pap smear or HPV-DNA test. Our study, therefore, questions the place of HPV DNA test in women with PCB. Material and Methods: The clinical data of 212 women with persistent PCB and negative cytology or negative HPV DNA test referred to colposcopy, between January 2010 and June 2019, were retrospectively evaluated. Results: Among the 212 PCB patients, 161 (75.9%) were cytology negative and 51 (24.1%) were HPV DNA test (n=40) or co-test (n=11) (negative for HPV DNA test and cytology) negative. There were no cases of invasive cancer. The women referred with negative cytology were more likely than those with negative HPV DNA to have CIN (21/161 (13%), 1/51 (1.9%) p=0.042. Seven women (4.3%) were diagnosed with high-grade cervical dysplasia in the negative cytology group. None of the patients in the HPV DNA negative group was diagnosed with high-grade cervical dysplasia. Conclusion: Our data show that a normal Pap smear cytology in women with PCB does not rule out the possibility of HSIL. HPV DNA testing is a useful triage test to determine if colposcopy referral is required in the context of post-coital bleeding with negative smear test.

The feasibility of new HPV/DNA test as a primary cervical cancer screening method among 35- years- old ever-married women in Kalutara district; a cross-sectional study

Background Cervical cancer is the second commonest female cancer in Sri Lanka. Two major drawbacks of the present cervical cancer screening programme are the suboptimal sensitivity of the pap smear and the low coverage. The objective of the study is to determine the feasibility of a new HPV/DNA test among 35 -years -old ever-married women in a district of Sri Lanka. Method A community based descriptive cross-sectional study was conducted from 1stof July 2018 to 30th November 2018 in the public health divisions called Medical Officer of Health (MOH) areas of Kalutara district. The study population is comprised of ever-married women 35 years of age. Three women from each cluster (n = 413) were selected by consecutive sampling. A total of 918 women were recruited. HPV/DNA cervical specimen collection (n = 822) was carried out. Cervical specimens were tested by two cytoscreeners with the cobas 4800 PCR based screening machine. Clients’ perceptions and prevalence were assessed. The follow-up of women with positive HPV/DNA screening results was carried out. The operational and technical feasibility of the screening test were assessed. Data entry was done by using the statistical package IBM SPSS version 20. Results Overall response rate was 91.1% (n = 836). Clients’ perception was highly positive for HPV/DNA screening test procedure (99.9%, n = 821) and 99.6% (n = 819) of clients had mentioned that the HPV/DNA screening test is worthwhile to be incorporated into the National Cervical Cancer Screening program. The prevalence of HPV was 6.2% (95%CI: 6.18–6.22%). The coverage of the HPV/DNA screening was 89.5%(n = 822). Invalid results reported were 0.12% (n = 1). The percentage of HPV/DNA test positive women who underwent pap test within 3 months of the initial screening was 100% (n = 51), while the percentage of women who attempted to get a colposcopy within the 1 month of referral was 86.7% (n = 13). Conclusions HPV/DNA test implementation as a primary cervical cancer screening method is feasible among the 35- year age cohort of ever- married women in Kalutara district. It is necessary to further attempt alternative methods of cobas 4800 HPV/DNA test, which would be much suitable for resource-limited settings.