Cervical HPV Testing Research Articles

Feasibility and Accuracy of Menstrual Blood Testing for High-risk Human Papillomavirus Detection With Capture Sequencing

High-risk human papillomavirus (hrHPV) persistent infection is the major etiology of cervical precancer and cancer. Noninvasive self-sampling HPV testing is a promising alternative cervical cancer screening for avoiding stigma and improving patient willingness to participate. To investigate the feasibility and accuracy of menstrual blood (MB) hrHPV capture sequencing in hrHPV detection. This cohort study collected 137 sanitary pads from 120 women who were premenopausal and had hrHPV as detected by cervical HPV GenoArray testing. Patients were recruited from September 1, 2020, to April 1, 2021, at Central Hospital of Wuhan, China. Target capture sequencing was performed to determine hrHPV genotypes in MB. Sanger sequencing was performed as the criterion standard for detecting hrHPV genotypes among enrolled women. Data were analyzed from April 1 through June 1, 2021. Complete concordance, incomplete concordance, and discordance of MB hrHPV capture sequencing and conventional HPV testing were defined according to genotype overlapping levels. Concordance of the 2 detection methods and comparative power of MB hrHPV capture sequencing during different menstrual cycle days (MCDs) were the main outcomes. A total of 120 enrolled women with hrHPV (mean [SD; range] age, 33.9 [6.9; 20.0 -52.0] years) provided 137 sanitary pads. The overall concordance rate of MB hrHPV capture sequencing and cervical HPV testing was 92.7% (95% CI, 88.3%-97.1%), with a κ value of 0.763 (P < .001). Among 24 samples with incomplete concordance or discordant results, 11 samples with additional hrHPV genotypes (45.8%), 5 true-negative samples (20.8%), and the correct hrHPV genotypes of 2 samples (8.3%) were correctly identified by MB hrHPV capture sequencing. MB hrHPV detection of hrHPV was equivalent on different MCDs, with an MB hrHPV-positive rate of 27 of 28 patients (96.4%) for MCD 1, 52 of 57 patients (91.2%) for MCD 2, 27 of 28 patients for MCD 3, 4 of 4 patients (100%) for MCD 4, and 3 of 3 patients (100%) for MCD 5 (P = .76). The sensitivity of the MB hrHPV capture sequencing was 97.7% (95% CI, 95.0%-100%). These findings suggest that MB hrHPV capture sequencing is a feasible and accurate self-collected approach for cervical cancer screening. This study found that this method is associated with superior performance in identification of HPV genotypes and true-negative events compared with cervical HPV testing.

The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer.

We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

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.

Detection of high-risk human papillomavirus RNA in urine for cervical cancer screening with HPV 16 & 18/45 genotyping

ObjectiveTo detect high-risk human papillomavirus (hrHPV) messenger-RNA (mRNA) in urine samples, compare their concordance with cervical samples including HPV 16 & 18/45 genotyping, and to determine the utility in detecting ≥ CIN 2 lesions. MethodsA cohort of 189 non-pregnant patients (age ≥ 25) was recruited in three groups: Group 1 with abnormal pap-smears and hrHPV positivity, Group 2 with normal pap-smears and hrHPV positivity, and Group 3 with normal pap-smears and hrHPV negativity. Urine samples were tested for hrHPV-mRNA and subsequent hrHPV-mRNA genotype if positive. High-risk HPV detection and genotyping were performed using Aptima assays which are validated for cervical HPV testing. Colposcopy results from groups 1 & 2 were analyzed. ResultsThe sensitivity of urine hrHPV-mRNA detection was 31.5% while the specificity and PPV were above 95% (96.9% & 95.1% respectively) (p < 0.001). The kappa agreement with cervical samples was fair (0.22, p = 0.04). The sensitivity and specificity of urine hrHPV-mRNA genotyping were 20.0% & 100% respectively (p < 0.001) with 100% genotype-specific concordance. The kappa agreement with cervical samples was fair (0.25, p = 0.16). For urine hrHPV-mRNA detection of ASC-H/HSIL when grouped by age ≥ 30, the sensitivity and specificity were 45.4% & 63.9% respectively (p = 0.009). For urine hrHPV-mRNA detection of ≥ CIN 2 for all ages, the sensitivity and specificity were 45.5% & 75.0% respectively (p = 0.03). ConclusionUsing the Aptima Assay, urine hrHPV-mRNA detection is suboptimal for cervical cancer screening but given the high specificity, it has the potential to identify high-grade lesions (≥ CIN 2). Urine hrHPV-mRNA genotyping via this modality is not beneficial in triage settings of normal or abnormal cytology to determine the need for colposcopy.

Positive Correlation Between Clearance of High-Risk Human Papillomavirus and Lack of Residual Disease After Loop Excision of the Transformation Zone in Early Stage Cervical Cancer.

In cervical cancer, a number of pathological parameters have been explored for their utility in tailoring a less aggressive approach for patients with low-risk early stage disease. We examined whether, in patients with cervical cancer stage IA1 to IB1, diagnosed by loop excision of the transformation zone (LLETZ), positive for high-risk human papillomavirus (hrHPV), clearance of hrHPV after LLETZ correlates with absence of residual disease at the final pathology after definitive or further surgery. Data were collected from patients diagnosed with early stage invasive cervical cancer and positive hrHPV DNA, who had a repeat cervical HPV test 3 to 12 weeks after LLETZ and before final surgical treatment. We compared characteristics of patients with post-LLETZ negative and positive hrHPV. Of 28 patients, 13 were post-LLETZ negative hrHPV; of these, 11 did not have residual cancer in the final pathological specimen; two patients had cervical intraepithelial neoplasia 3. Of the 15 women who had post-LLETZ positive hrHPV, 10 had residual cancer in the final pathological specimen and 3 had cervical intraepithelial neoplasia or adenocarcinoma in situ; only 2 were negative for cancer. The post-LLETZ hrHPV test shows a sensitivity of 86.7% and specificity of 84.6%. Clearance of hrHPV from the cervix after LLETZ was found to correlate with the absence of residual cancer in the final surgical specimen. Testing for hrHPV post-LLETZ might serve as a new parameter for risk assessment and tailoring of a less radical operation in women with early stage cervical cancer.

Cervical HPV Infection in Female Sex Workers: A Global Perspective

Introduction: Approximately 291 million women worldwide are HPV DNA carriers. Studies have indicated that having multiple sexual partners may lead to higher HPV transmission. Thus female sex workers (FSWs) may be at greater risk of infection compared to the general population. Herein we review publications with data on FSW cervical HPV test results. We also examine variations of HPV prevalence and risk behaviors by region. Knowledge of prevalent HPV types in FSWs may lead to improved prevention measures and assist in understanding vaccination in high-risk groups.Methods: We conducted a review of the literature by searching PUBMED using the terms “prostitution” or “female sex workers”, “human papillomavirus” or “HPV”, and “prevalence” or “PCR” to find articles. We excluded studies without HPV testing or HPV type specific results, or unconventional HPV testing.Results: A total of 35 peer-reviewed publications were included in our review. High risk HPV types 16 and 18 ranged from 1.1-38.9‰ in prevalence. In addition to high-risk HPV types, newer studies reported non-carcinogenic HPV types also of high prevalence. The most prevalent HPV types reported among FSWs included HPV 6 (11.5%), 16 (38.9%), 18 (23.1%), 31 (28.4%), 52 (32.7%), and 58 (26.0%).Conclusions: Female sex workers have an overall high prevalence of HPV infection of high-risk types as evident through various testing methods. FSWs are thought to be at increased risk of cervical cancer because of high HPV exposure. This highlights the need for HPV and cervical prevention campaigns tailored to FSWs.

Genetic polymorphisms in the promoters of IL-6 and IL-10 in CIN and cervical cancer patients

To compare the PCR detection rates of high risk human papillomavirus DNA in self-collected urine and cervical scrapes during follow-up of patients treated for HG-CIN by laser CO2 conization.52 women who submitted to laser conization for HG-CIN were enrolled into this prospective follow-up study receiving liquid-based cytology and HR-HPV testing by PCR assay on self-collected urine and cervical scrapes before and at 3, 6 and 12 months after treatment. Diagnostic accuracy and predictive values for treatment failure were evaluated for both urinary and cervical HPV testing and follow-up cytology.3 cases (5.8%) of recurrent HG-CIN occurred during follow-up. Positive margins and HR-HPV persistence resulted to significant risk factors for recurrence (p = 0.01). The overall concordance on HR-HPV detection between paired urine and cervical samples was 96.6% and discord trend between agreement rates during follow-up were excluded by overall fixed-effect index (OR 1.03; 95% CI 0.62–1.70). No difference was observed comparing the three- and six-month cumulative sensitivity and NPV for recurrent disease of urinary and cervical HPV detections, with an increase of 5.6% in specificity associated with urinary testing.PCR detection of HR-HPV in paired urine and cervical samples during follow-up revealed an excellent concordance, suggesting a potential equivalent role of the two methods within post-treatment follow-up. In our experience HPV testing on self-collected urine was more sensitive than cytology and more specific than cervical HPV detection to predict treatment failure. Larger studies are needed to definitively establish the role of urine-based HPV testing during follow-up.

PCR detection rates of high risk human papillomavirus DNA in paired self-collected urine and cervical scrapes after laser CO2 conization for high-grade cervical intraepithelial neoplasia

Objective To compare the PCR detection rates of high risk human papillomavirus DNA in self-collected urine and cervical scrapes during follow-up of patients treated for HG-CIN by laser CO2 conization. Patients and methods 52 women who submitted to laser conization for HG-CIN were enrolled into this prospective follow-up study receiving liquid-based cytology and HR-HPV testing by PCR assay on self-collected urine and cervical scrapes before and at 3, 6 and 12 months after treatment. Diagnostic accuracy and predictive values for treatment failure were evaluated for both urinary and cervical HPV testing and follow-up cytology. Results 3 cases (5.8%) of recurrent HG-CIN occurred during follow-up. Positive margins and HR-HPV persistence resulted to significant risk factors for recurrence ( p = 0.01). The overall concordance on HR-HPV detection between paired urine and cervical samples was 96.6% and discord trend between agreement rates during follow-up were excluded by overall fixed-effect index (OR 1.03; 95% CI 0.62–1.70). No difference was observed comparing the three- and six-month cumulative sensitivity and NPV for recurrent disease of urinary and cervical HPV detections, with an increase of 5.6% in specificity associated with urinary testing. Conclusions PCR detection of HR-HPV in paired urine and cervical samples during follow-up revealed an excellent concordance, suggesting a potential equivalent role of the two methods within post-treatment follow-up. In our experience HPV testing on self-collected urine was more sensitive than cytology and more specific than cervical HPV detection to predict treatment failure. Larger studies are needed to definitively establish the role of urine-based HPV testing during follow-up.