High-risk Human Papillomavirus DNA Detection Research Articles

Epidemiology of human papillomavirus infection in women from Xiamen, China, 2013 to 2023.

Cervical cancer is primarily caused by HPV infection. The epidemiology of HPV infection in specific areas is of great meaning of guide cervical cancer screening and formulating HPV vaccination strategies. Here, we evaluated the epidemiological characteristics of HPV infection in Xiamen population. In total, 159,049 cervical exfoliated cell samples collected from female outpatients in Women and Children's Hospital, School of Medicine, Xiamen between January 2013 and July 2023 were analyzed. HPV DNA detection was performed using HPV genotyping kits (Hybribio Limited Corp, China). An analysis was conducted on the prevalence of HPV infection, taking into account factors such as age, year, and multiple patterns of HPV infection. The differences in prevalence among age groups and years were compared using χ2 test. The overall prevalence of any 21 HPV genotypes was 18.4%, of which the high-risk HPV (HR-HPV) positive rate was 14.6%. The age-specific prevalence of HPV infection showed a bimodal distribution, with two distinct peaks, one at <25 years (31.2%) and the other at 60-64 years (32.9%). There was a downward trend in the prevalence of HPV infection over time, decreasing from 26.2% in 2013 to 14.5% in 2021, and then increasing to 19.0% in 2023. The five most prevent HR-HPV genotypes were HPV52 (4.0%), 58 (2.6%), 16 (2.5%), 51 (1.8%), and 39 (1.7%). Among the positive cases, 76.7% were detected with only one genotype and 23.3% with multiple genotypes. The most common co-infection was HPV52 + HPV58 (0.24%), followed by HPV16 + HPV52 (0.24%), HPV52 + HPV53 (0.21%), HPV52 + HPV81 (0.21%), HPV51 + HPV52 (0.19%), HPV16 + HPV58 (0.18%), and HPV39 + HPV52 (0.17%). The study provided the largest scale information on the recent epidemiological characteristics of HPV infection in Xiamen, and even in Fujian Province, China, which would support making the prevention and control strategies for cervical cancer in the region.

HPV Infection and Immunohistochemical Analysis of P16, P53, and PD-L1 Expression as Prognostic Biomarkers in Squamous Cell Anal Cancer Patients Receiving Definitive Radiotherapy/Chemoradiotherapy

The treatment of anal squamous cell carcinoma (SCC) with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has a high likelihood of success; nevertheless, treatment resistance and recurrence rates cannot be ignored. Therefore, we aimed to identify the relationship between immunohistochemical (IHC) evaluation, treatment response, and prognosis. This retrospective study included 42 patients with anal SCC treated with definitive RT/CRT at a single institution between 2006 and 2020. Detection of high-risk HPV-DNA and IHC analysis of p16, p53, and PD-L1 expression was performed from diagnostic formalin-fixed, paraffin-embedded (FFPE) biopsies. Positive staining was accepted as >5% in tumor cells for p16 and p53 expression in addition to ≥1% combined positive score (CPS) [(PD-L1 positive tumor, lymphocyte, macrophage count/total viable cell count) x100] for PD-L1 expression. Thirty patients (71.4%) had a complete response to definitive RT/CRT. Recurrence was observed in 16 (38.1%) patients, with 3 (7.1%) having locoregional recurrence (LRR), 6 (14.3%) having distant metastases (DM), and 7 (16.7%) having both LRR and DM. Twenty-four (57.1%) patients were alive. Thirty (71.4%) patients were HPV+, while 12 (28.6%) were HPV-. There was a significant correlation between HPV+ and p16+ status (p<0.001). HPV- status was associated with the male gender (p = 0.001). HPV- and p16- status were significantly associated with a lack of complete response to definitive RT/CRT (p<0.001, p<0.001, respectively). Furthermore, there was a significant relationship between lack of complete response and increased recurrence (p = 0.016) and distant metastases (p = 0.015). Ten of the 16 patients with recurrence were p53+; a significant correlation was found between recurrence and p53+ status (p = 0.006). Similarly, p53+ status was associated with increased LRR (p = 0.014). PD-L1 CPS ≥ 1% was found in 31 (73.8%) patients. PD-L1 positivity was significantly correlated with HPV+ (p = 0.026) and p16+ (p = 0.013) status. All 10 (23.8%) patients with LRR were PD-L1+; PD-L1 CPS ≥ 1% was associated with poor local control (p = 0.031). In univariate analysis, age [<65] (p = 0.049), complete response (p = 0.015), and HPV+ status (p = 0.010) were related to increased 5-year (y) overall survival (OS); complete response (p = 0.001), HPV+ status (p = 0.025) and p53- status (p = 0.010) were associated with increased 5-y disease-free survival (DFS). In multivariate analysis, age [<65] (p = 0.010) and HPV+ status (p = 0.002) were significant prognostic factors for 5-y OS, whereas complete response (p = 0.007) and p53- status (p = 0.038) were significant prognostic factors for 5-y DFS. Patients with HPV- status and/or poor prognostic biomarkers should be identified at diagnosis. Thus, better outcomes can be achieved with different treatment options, such as combining immunotherapy and standard CRT.

Diagnostic study of human papillomavirus DNA detection in cervical and vaginal samples using the filter paper card.

To determine the accuracy of high-risk human papillomavirus (HPV) DNA samples on filter paper in comparison to specimen transport medium (STM). This was a cross-sectional diagnostic study of 42 consecutive women who were prospectively recruited. Each had self-collected vaginal samples on filter paper, physician-collected cervical samples on filter paper, and physician-collected cervical samples in STM. HPV DNA testing was performed with a Hybrid Capture 2 system (Qiagen). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and agreement of filter paper methods with the standard procedure were calculated. The overall prevalence of HPV in STM was 67.5%. Detection of HPV DNA in the physician-collected cervical samples on filter paper had a sensitivity of 77.8%, a specificity of 100%, a PPV of 100%, and an NPV of 68.4%. The patient's self-sampling on filter paper had a sensitivity of 66.7%, a specificity of 100%, a PPV of 100%, and an NPV of 59.1%. The agreement between STM method and physician-collected sample on filter paper was substantial, (κ = 0.695, P < 0.001), while the agreement between STM and self-collected samples on filter paper was moderate (κ = 0.565, P < 0.001). Most patients reported that self-collection was acceptable (100%), painless (95%), and not embarrassing (95%). Filter paper, with dried self-collected vaginal samples, can be used to detect high-risk HPV with acceptable accuracy.

Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome.

Polyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up. Glutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up. Being BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN. Thus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa.

Abstract 81: The Introduction of a High Risk HPV DNA Test for the Cervical Cancer Screening Among Mongolian Women

Abstract Purpose: A global strategy developed by the World Health Organization aims to reduce cervical cancer burden by screening 70% of women with high performance tests at least twice during their lifetime. While Mongolia has implemented a PAP test-based cervical cancer screening program over the past few decades, cervical cancer remains the leading cause of death in the country. Therefore, it is necessary to introduce high-risk HPV DNA detection tests in cervical cancer screening program. Methods: Cervical screening was conducted in 6 districts of the UB and in 4 regional provinces between March 01 and July 01, 2019. A high risk HPV DNA test was conducted on all women using the careHPV test, and then all positive samples were double-tested using the PAP test. All positive women were followed by HPV genotyping test and colposcopy with direct biopsy or endocervical curettage as necessary. Results: A total of 2725 women were screened for HPV DNA, with 8.5%(239) of these detecting high risk HPV DNA, and 61% (138) of positive results having a negative result for intraepithelial neoplasia as determined by PAP tests. It was determined that 10% of samples contained atypical squamous cells of undetermined significance, 4% contained atypical squamous cells of unknown significance, and cannot exclude high grade, 17% of the samples contained low grade squamous intraepithelial lesions, and 10% contained high grade squamous intraepithelial lesions. A colposcopy examination was performed on 181 women who were high-risk HPV DNA positive. An abnormal colonoscopy result was observed in 18% of the women, for which biopsies were taken. A total of 31% of them were confirmed with CIN I, 31% with CIN II, 9% with CIN III, 11% with CIS, and 6% with SCC. Additionally, 105 high-risk HPV DNA-positive samples were genotyped for HPV. There were 25.7% of individuals who were found to have HPV genotype 16, 4.7% who were found to have HPV genotype 18, and 69.6% who were found to have other high-risk genotypes. Conclusion: By incorporating high-risk HPV DNA tests into cervical cancer screening program, its coverage and effectiveness could be increased. Citation Format: Enkhjargal Bayarsaikan. The Introduction of a High Risk HPV DNA Test for the Cervical Cancer Screening Among Mongolian Women [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 81.

Human papillomavirus testing on self-collected samples to detect high-grade cervical lesions in rural Bhutan: The REACH-Bhutan study.

"REACH-Bhutan" aimed to evaluate the feasibility and clinical performance of a community-based screening program for cervical cancer in rural Bhutan using self-collected samples for high-risk human papillomavirus (HR-HPV) testing. In April/May 2016, 2590 women aged 30-60 years were screened across rural Bhutan by providing a self-collected sample for careHPV testing. All careHPV-positive women, plus a random sample of careHPV-negative women, were recalled for colposcopy and biopsy. Self-samples also underwent GP5+/6+ polymerase chain reaction (PCR)-based HR-HPV DNA detection and genotyping. Cross-sectional screening indices were estimated against histological high-grade squamous intraepithelial lesions or worse (hHSIL+), including imputation of hHSIL+ in women without colposcopy. HR-HPV positivity was 10.2% by careHPV and 14.8% by GP5+/6+ PCR. Twenty-two cases of hHSIL+ were histologically diagnosed, including one invasive cancer; an additional 7 hHSIL+ were imputed in women without colposcopy. HR-HPV testing by GP5+/6+ showed higher sensitivity for hHSIL+ (89.7%, 95% CI 72.6-97.8) than careHPV (75.9%, 95% CI 56.5-89.7). Negative predictive value was also slightly higher for GP5+/6+ (99.9%, 95% CI 99.6-100) than careHPV (99.7%, 95% CI 99.4-99.9). Specificity, however, was lower for GP5+/6+ (86.1%, 95% CI 84.6-87.4) than careHPV (90.6%, 95% CI 89.4-91.7), as was positive predictive value (6.9%, 95% CI 4.5-9.9 vs. 8.5%, 95% CI 5.4-12.6). Of 377 HR-HPV-positive women by GP5+/6+, 173 (45.9%) were careHPV-positive, including 54.7% HPV16-positive and 30.2% HPV18-positive women. The final REACH-Bhutan results show that screening for cervical cancer with self-collection of samples and HR-HPV testing, in addition to our previous report of achieving high participation, can also perform well to detect women with hHSIL+.

Association between human papillomavirus and oral cancer: a literature review.

HPV plays a vital role in the development of cervical cancers and oropharyngeal cancers, but it is controversial whether HPV is involved in oral cancer development and to what extent. In this review, the clinical characteristics, diagnosis, treatment, and prognosis of HPV-positive oral cancers are summarized, and the mechanisms of HPV-related oral cancer development are discussed. HPV DNA positivity rates are 20-30% in oral squamous cell carcinoma (OSCC), and HPV16 is the most common high-risk HPV. E6/E7 mRNA positivity rates are 2-6% in OSCC. Detection of both high-risk HPV DNA and E6/E7 mRNA is recommended to determine the presence of active HPV, in agreement with high-risk HPV infection in OSCC. Surgical treatment is the first-line therapy for HPV-positive and -negative oral cancer, but there is no unified view about the prognosis of HPV-positive OSCC patients. HPV16 may play a vital role in malignant transformation in oral epithelial dysplasia, and a model of synergistic carcinogenic impact of HPV and tobacco smoking is predicted. Additionally, it is hypothesized that there are different HPV-associated oral cancers, such as integrated HPV DNA-positive OSCC with stable E6/E7 expression and episomal HPV DNA-positive OSCC. In summary, the role of HPV in oral carcinogenesis seems to be limited because of the low E6/E7 positivity in OSCCs; however, episomal HPV DNA may play a vital role in the malignant transformation of HPV-positive oral premalignant lesions. Further investigation is required to promote new insights into the role of episomal HPV DNA in oral carcinogenesis.

Utilizing first void urine for high-risk HPV testing for cervical cancer screening in HIV-positive women in Katete, Zambia

BackgroundThe World Health Organization targets to screen 70% of women worldwide twice for cervical cancer by the year 2030, first by age of 35, and again by the age of 45. However, with the current low screening coverage in many developing countries, this may not be achieved because the invasive sampling method is unacceptable to some. In Zambia, for instance, despite the availability of free cervical cancer screening through the establishment of the Cervical Cancer Prevention Programme, some women are still reluctant to go for screening. First void urine sampling is non-invasive and thus has the potential to increase screening coverage. We aimed to determine the performance of first void urine for high-risk human papillomavirus DNA detection, the prevalence of high-risk HPV, and the acceptability of first void urine sampling.Materials and methodA comparative cross-sectional study was conducted among 100 HIV- infected women at St Francis’ Hospital in Zambia, attending the routine HIV/AIDS services and cervical cancer screening. 17 mL of first void urine sample collected by each participant was immediately mixed with 3 mL of 0.5 M EDTA preservative solution before cervical sample collection by the clinician. For testing, 2 mL of first void urine and 1 mL of the cervical sample were tested using the GeneXpert platform. An interview-based questionnaire was used to gather data on the acceptability of first void urine sampling. Data was analyzed using Stata version 17.ResultsThe mean age of the participants was 42.58 years (95% CI 40.98–44.19; SD 8.01). High-risk HPV prevalence was 34% (95% CI 24%-43.9%) in both cervical and first void urine samples. Sensitivity and specificity were 84.8% (95% CI 68.1%–94.9%) and 92.3% (83%–97.5%), respectively. There was 89.80% agreement between the samples (κ = 0.77; 95% CI 0.64–0.91). First void urine sampling was highly accepted.ConclusionHigh-risk HPV DNA can be detected in first void urine samples using the GeneXpert, with a substantial agreement with cervical samples. An affordable preservative such as Ethylenediamine tetraacetic acid can prevent DNA degradation. With optimization, first void urine sampling has the potential to increase screening coverage.

Prevalence of HPV infection and cervical intraepithelial lesions in HIV positive and negative women in the city of Florianopolis

Introduction: The human papillomavirus (HPV) is the most common sexually transmitted infection among women. The HPV of high oncogenic risk, associated with other factors, presents a risk of progressing to a precancerous lesion of the uterus and even cancer. Such an evolution is related to the persistence of the infection and other factors, mainly those that interfere with women’s immunity. The immunosuppression caused by HIV infection is an important factor for viral persistence and the onset of these lesions. Objectives: To compare the prevalence of HPV infection and cervical intraepithelial lesions in HIV-positive and negative women and describe the possible associated risk factors. Methods: The sample consisted of 50 HIV positive women (study group) and 50 HIV negative women (control group) recruited from the public health system of Florianópolis from January to April 2022. Cervical samples were collected for cytological analysis and for the detection of high-risk oncogenic HPV DNA by polymerase chain reaction (PCR). Categorical variables were compared using the chi-square test, with a significance level set at 5% Results: HPV infection was more prevalent in the control group; however, HIV positive women presented higher frequency of intraepithelial lesions diagnosed on cytology. Factors such as higher number of sexual partners, depression and smoking were more frequent in the group of HIV positive women. CD4 T cells lower than 200 cells/mm3 was associated with a higher number of altered Pap smears and a positive HPV DNA test. The use of combination antiretroviral therapy and undetectable viral load were associated with more frequent normal cytology and undetected HPV DNA. Conclusion: The prevalence of cervical intraepithelial lesions in HIV-infected women is higher than among women without the infection. The presence of HIV infection was the most important risk factor associated with the development of cervical lesions.

Cobas® 4800 HPV test is accurate for detecting high risk Human Papillomavirus from urine samples at dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia

HIGHLIGHTS 1. The presence of Human Papillomavirus (HPV) can be detected using urine samples, as compared to cervical samples, by means of Cobas® 4800 HPV test.2. The concordance between cervical and urine samples for HPV DNA was found as much as 84.72%.3. Urine samples subjected to Cobas® 4800 HPV test is helpful to treat HPV infection. ABSTRACT Objective: To find the accuracy, sensitivity, specificity, as well as predicted values, both positive and negative, of urine samples using Cobas® 4800 in detecting high risk Human Papillomavirus. Materials and Methods: This study was a cross-sectional study with a total of 72 samples taken from medical records of hrHPV DNA examination with Cobas® 4800 in 2017-2020. Study subjects were called for re-examination of urine samples and cervical samples using Cobas® 4800. Samples with positive hrHPV DNA in the cervix, urine, or both were examined for cervical fluid-based cytology (LBC). Data were analyzed using Chi-square. Results: Overall, 84.72% agreement was detected through specimens of urine and cervical mucus tested of hrHPV DNA with Cobas® 4800. In all samples, a significant rate of concordance detection of hrHPV DNA with Cobas® 4800 was reported (ka = 0.62; 95% IC: 39-84). In this population, in determining the presence of hrHPV DNA in cervical and urine specimens, it was found that the sensitivity, specificity, positive predictive value and negative predictive value were respectively 87.5% (95% IC: 64–97%), 84% (95% IC: 72–91%), 60.9% (95% IC: 40.8–77.8%), and 96 % (95% IC: 86.3–98.9%). Conclusion: The presence of hrHPV infection in the cervix can be determined by detecting hrHPV DNA in the urine. According to these findings, urine samples subjected to the Cobas® 4800 HPV test may be helpful for the clinical treatment of HPV infection.

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women.

Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.

Prevalence of HPV-DNA and E6 mRNA in lung cancer of HIV-infected patients

HIV-infected individuals could be at a greater risk for developing lung cancer than the general population due to the higher prevalence in the former of human papillomavirus (HPV) in the oral cavity and higher smoking rates. Our aim was to assess HPV prevalence and E6 viral oncogene transcription in lung cancer samples from HIV-infected individuals. This was a single-center, retrospective study of a cohort of HIV-1-infected patients diagnosed with and treated for lung cancer. Pathological lung samples archived as smears or formalin-fixed paraffin-embedded blocks were subjected to HPV genotyping, detection of human p16 protein and assessment for HPV E6 mRNA expression. Lung cancer samples from 41 patients were studied, including squamous cell carcinoma (32%), adenocarcinoma (34%), non-small cell cancer (27%), and small cell cancer (7%). HPV DNA was detected in 23 out of 41 (56%, 95% CI 41–70%) of samples and high-risk (HR)-HPV types were detected in 16 out of 41 (39%, 95% CI 26–54%), HPV-16 being the most prevalent [13/16 (81.3%, 95% CI 57.0–93%]. In samples with sufficient material left: expression of p16 was detected in 3 out of 10 (30%) of HR-HPV DNA-positive tumors and in 3 out of 7 (43%) of the negative ones; and E6 mRNA was detected in 2 out of 10 (20%) of HPV-16-positive samples (squamous lung cancers). These two patients had a background of a previous HPV-related neoplasia and smoking. HR-HPV DNA detection was prevalent in lung cancers in HIV-infected patients. However, viral oncogene expression was limited to patients with previous HPV-related cancers.

Survival With Cemiplimab in Recurrent Cervical Cancer

(Abstracted from N Engl J Med 2022;386(6):544–555) Despite widespread implementation of cervical cancer screening and prevention programs including cytologic assessment and high-risk human papillomavirus DNA detection as well as effective vaccines, the incidence of cervical cancer remains high. Treatment varies based on stage and grade and involves a combination of surgery, platinum-based chemotherapy, bevacizumab, chemoradiation, and intracavitary brachytherapy.

Detection of Host Cell Gene/HPV DNA Methylation Markers: A Promising Triage Approach for Cervical Cancer

Cervical cancer is the most prevalent gynecologic malignancy, especially in women of low- and middle-income countries (LMICs). With a better understanding of the etiology and pathogenesis of cervical cancer, it has been well accepted that this type of cancer can be prevented and treated via early screening. Due to its higher sensitivity than cytology to identify precursor lesions of cervical cancer, detection of high-risk human papillomavirus (HR-HPV) DNA has been implemented as the primary screening approach. However, a high referral rate for colposcopy after HR-HPV DNA detection due to its low specificity in HR-HPV screening often leads to overtreatment and thus increases the healthcare burden. Emerging evidence has demonstrated that detection of host cell gene and/or HPV DNA methylation represents a promising approach for the early triage of cervical cancer in HR-HPV-positive women owing to its convenience and comparable performance to cytology, particularly in LMICs with limited healthcare resources. While numerous potential markers involving DNA methylation of host cell genes and the HPV genome have been identified thus far, it is crucial to define which genes or panels involving host and/or HPV are feasible and appropriate for large-scale screening and triage. An ideal approach for screening and triage of CIN/ICC requires high sensitivity and adequate specificity and is suitable for self-sampling and inexpensive to allow population-based screening, particularly in LMICs. In this review, we summarize the markers of host cell gene/HR-HPV DNA methylation and discuss their triage performance and feasibility for high-grade precancerous cervical intraepithelial neoplasia or worse (CIN2+ and CIN3+) in HR-HPV-positive women.

A comparison of high-risk human papillomavirus DNA detection between urine and cervical sample testing in women with abnormal Pap smears.

To compare the clinical performance of high-risk human papillomavirus (hrHPV) DNA detection between urine and cervical samples collected from the same patient for the detection of CIN2+ lesions (high-grade squamous intraepithelial lesions or cervical cancer lesions). The secondary objectives were to evaluate agreement among hrHPV genotypes and to compare patient satisfaction between urine and cervical sample collection. This prospective cross-sectional study enrolled 96 women with abnormal cervical cytology who attended the colposcopy clinic at Siriraj Hospital (Bangkok, Thailand) between July 2016 and January 2017. Self-collected random-voiding and first stream urine samples were collected into a universal sterile urine container and immediately mixing with preservative before the pelvic examination. Cervical tissue sampling was performed according to standard treatment guidelines. Both specimens were sent for extraction and detection of hrHPV by Anyplex II HPV high-risk testing. Study patients were surveyed to compare patient satisfaction between urine and cervical sample collection. Carcinogenic hrHPV positive rate was 73% in urine samples and 81% in cervical samples. The sensitivity for HPV in the detection CIN2+ was high in both the urine and cervical groups at 86.2% and 94.8%, respectively. Agreement between the urine and cervical groups for HPV 16 or 18 detection was high, with kappa values of 0.86 for subtypes 16/18. Urine specimen collection had significantly higher satisfaction and acceptability than cervical specimen collection. Urine hrHPV testing by real-time polymerase chain reaction demonstrated high sensitivity and accuracy for the detection of CIN2+ lesions, with very good agreement when compared with cervical sample testing.

Preliminary study of the use of E6/E7mRNA detection in screening and triage management of HR-HPV infection during pregnancy.

BackgroundDetection of E6 and E7 mRNA load of high-risk human papillomavirus (HR-HPV) infection during pregnancy was compared with conventional cytopathology and DNA detection by pathological examination as colposcopy to evaluate the application of E6 and E7 mRNA detection in the diagnosis and management in HR-HPV infection for high -grade cervical lesions during pregnancy.MethodsFrom January 2014 to June 2019, 1,058 pregnant women of childbearing age who were filed for regular obstetrics in the Department of Obstetrics and Gynecology, Xuanwu Hospital of Capital Medical University, were separately assessed using cervical liquid-based cytology and HPV DNA detection. If the results were abnormal, colposcopy was performed as a follow-up. The presence of HR-HPV E6/E7 mRNA fragments was detected through the HR-HPV E6/E7 mRNA test, and monitored at the same time as colposcopy. The diagnostic efficacy of the HR-HPV DNA test versus the HR-HPV E6/E7 mRNA test for high-grade cervical lesions during pregnancy was compared.ResultsThe positive rate of HR-HPV E6/E7 mRNA detection in the overall cervical intraepithelial neoplasia (CIN) and above during pregnancy was lower than that with HR-HPV DNA detection, and there was a significant statistical difference between the two methods. In CIN I and normal or inflammatory results, the positive rate of HR-HPV E6/E7 mRNA detection was lower than that of HR-HPV DNA detection, while in the results of CIN II and CIN III, the positive rate of the two was not significantly different. HR-HPV E6/E7 mRNA detection is the same as HR-HPV DNA detection, both of which increased with the severity of cervical lesions, and the positive rate increased. In cases of maintenance or progression of cervical lesions, the positive rate of HR-HPV E6/E7 mRNA detection during pregnancy can reach 81.8%. High-grade cervical lesions during pregnancy had a higher rate of reversal to a lower level after delivery.ConclusionsThe results suggested that the use of HR-HPV E6/E7 mRNA detection in cases of positive HR-HPV DNA detection can significantly improve the diagnostic specificity of CIN II and above high-grade cervical lesions.

Independent association of marijuana use and poor oral hygiene with HPV-negative but not HPV-positive head and neck squamous cell carcinomas.

Sexual behavior is associated with human papillomavirus (HPV)-positive head and neck cancer, whereas tobacco and alcohol use are associated with HPV-negative cancer. A case-control study was designed to investigate additional demographic and behavioral factors independently associated with these distinct oral cancers. From 2011 to 2014, 249 newly diagnosed oral cavity and oropharyngeal squamous cell carcinoma (OSCC) cases were matched (1:2) on age, gender, and self-identified race to 498 controls without a cancer history attending the outpatient otolaryngology clinic at The Ohio State University in Columbus. Cases were stratified by detection of high-risk HPV DNA and RNA in tumors. Demographic and behavioral data were collected using an audio computer-assisted self-interview, and associations with HPV-positive versus HPV-negative OSCCs were investigated by use of univariable and multivariable conditional logistic regression models. After adjustment for oral sexual behavior, the odds of HPV-positive cancer decreased with the patient's years of education. Annual income, tobacco smoking, alcohol drinking, marijuana smoking, and poor oral hygiene were not associated with HPV-positive OSCC. In contrast, the odds of HPV-negative OSCC increased independently with decreased annual income, decreased with a high number of marijuana hit-years, and increased with fewer than annual dental visits after adjustment for lifetime tobacco and alcohol use. Sexual behavior and education were not associated with HPV-negative OSCC. The distinct risk-factor profiles for HPV-positive and HPV-negative OSCC are confirmed and extended in this case-control study, thus supporting 2 principal etiological pathways for OSCC development. Sexually acquired human papillomavirus (HPV) infection is an established cause of tonsil and base of tongue cancers. This study compared and contrasted risk factors for HPV-positive and HPV-negative oral cancers. Low number of years of education and sexual behavior are associated with HPV-positive cancer. In contrast, low annual income, infrequent dental visits, and tobacco and alcohol use are associated with HPV-negative cancers. Long-term marijuana use appears protective for HPV-negative cancer. Public health efforts to address these modifiable risk factors may prevent oral cancer.

Neovaginal and Anal High-Risk Human Papillomavirus DNA Among Thai Transgender Women in Gender Health Clinics.

Although human papillomavirus (HPV)-related lesions in the neovagina of transgender women have been well documented, information on high-risk HPV (hrHPV) in the neovagina has been very limited. The objective of this study was to determine hrHPV DNA detection rate in the neovagina of transgender women. Neovaginal and anal swab were collected in liquid-based cytology fluid from transgender women visiting Gender Health Clinic and Tangerine Community Health Clinic in Bangkok, Thailand. Samples were processed for hrHPV DNA (reported as subtypes 16 and 18 or the pooled result of subtypes 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) by automated real-time polymerase chain reaction and for neovaginal cytology according to the Bethesda system. Demographic data and sexual history were obtained, and physical examination was conducted. HIV status was obtained from existing medical records. Samples were collected from 57 transgender women (mean age, 30.4 years [interquartile range, 8 years]). From 35 of 57 valid neovaginal samples, 8 (20%) tested positive for hrHPV DNA. From 30 of 57 valid anal samples, 6 (19.4%) tested positive for hrHPV DNA. HIV status was known for 52 transgender women, 1 of which were HIV infected; neovaginal hrHPV was invalid in that patient. One of 5 transgender women visiting sexual health clinics in Bangkok was found to have hrHPV DNA in neovaginal and anal compartments. Studies are needed to look at incidence and persistence of hrHPV infection to inform anogenital precancerous and cancerous screening programs for transgender women.

Perianal warts as a risk marker for anal high-risk-human papillomavirus (HPV) detection and HPV-associated diseases.

Genital warts are the most common sexually transmitted infection (STI) and are caused by human papillomavirus (HPV). Persistent anal infection by oncogenic genotypes of HPV is a determinant for anal cancer. Currently, anal cancer screening is not widely implemented. Our aim is to evaluate the role of perianal warts as a risk marker for anal high-risk (HR) HPV detection and anal dysplasia. In this observational, retrospective, cohort study of attendees of a STI outpatient clinic between January 2010 and June 2018, all human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) who performed anal cytology, anal HPV DNA detection and anoscopy were included. A comparison was made between patients with and without perianal warts. Primary endpoint: proportion of patients with an abnormal anal cytology. Secondary endpoints: proportion of patients with (i) anal HR-HPV detection; (ii) anal HPV 16 detection; (iii) abnormal anal biopsy; and (iv) anal high-grade squamous intraepithelial lesion (HSIL). Seventy-eight individuals were included: 39 with perianal warts and 39 without perianal warts. Subjects with perianal warts more frequently had an abnormal anal cytology (71.8% vs. 38.5%; P=0.003). This group also had a higher rate of anal HPV 16 detection (38.5% vs. 12.8%; P=0.01). No differences were detected in the proportion of patients with anal HR-HPV detection, with an abnormal anal biopsy or with anal HSIL. Perianal warts was an independent risk factor for an abnormal anal cytology (OR: 7.2) and for anal HPV 16 detection (OR: 6.7). Given the high risk of anal cancer in HIV-positive MSM, effective screening strategies are greatly needed. This study suggests that the presence of perianal warts is a suitable risk marker for anal HPV 16 detection and anal dysplasia.

Targeting Viral DNA and Promoter Hypermethylation in Salivary Rinses for Recurrent HPV-Positive Oropharyngeal Cancer.

The incidence and survivorship of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) are increasing. Presence of HPV DNA and epigenetic alterations in salivary rinses are independently associated with clinical prognosis. We evaluated the utility of a combined panel in detecting disease recurrence during surveillance. We also assessed the assay's applicability in screening for HPV+ OPSCC. Retrospective cohort study. Two tertiary academic hospitals. Forty-nine patients with posttreatment OPSCC were enrolled. Separately, 21 treatment-naive patients and 40 controls were included in the screening analysis. Salivary rinses were obtained from these cohorts and biomarker levels were quantified. Receiver operative characteristic (ROC) curves and multivariate logistic models were used to assess performance of biomarker combinations. Eight patients (16.3%) in the posttreatment cohort developed locoregional recurrence. Recurrence was associated with alcohol use (odds ratio [OR], 6.12; 95% confidence interval [CI], 0.26-3.79) and advanced nodal disease (OR, 2.21; 95% CI, 1.52-3.01). A panel of HPV DNA and methylated EDNRB improved detection of recurrent disease (area under the curve [AUC], 0.88) compared to single markers (AUC, 0.69-0.78). Positive biomarkers preceded clinical detection by 2.4 ± 1.6 months and was associated with nearly 40-fold risk of recurrence (OR, 36.4; 95% CI, 1.15-45.22). Within the screening analysis, single biomarkers demonstrated moderate sensitivity and specificity (AUC, 0.59-0.83) in the detection of primary disease. A panel combining HPV DNA markers with methylated EDNRB and methylated PAX5 improved AUC to 0.93. Detection of high-risk HPV DNA or aberrant hypermethylation in oral rinses is associated with presence and recurrence of OPSCC. Targeting both markers in saliva may have utility in long-term surveillance.