Human Papillomavirus Detection Methods Research Articles

Low Frequency of Human Papillomavirus in Strictly Site-Coded Oral Squamous Cell Carcinomas, Using the Latest NHI/SEER-ICD Systems: A Pilot Observational Study and Critical Review.

Simple SummaryThe incidence of oropharyngeal squamous cell carcinomas (OPSCCs) has increased in the last decades, and this seems to be correlated to the infectious epidemiological trend of human papillomavirus (HPV). The prevalence of HPV-positive OPSCCs is approximately 70%, with involvement mainly of the tonsillar area. On the role of HPV in oral squamous cell carcinoma (OSCC), very few studies have investigated the prevalence of HPV in strictly site-codified OSCC, excluding the base of the tongue as distinct oropharyngeal entity. As a result, an inappropriate estimation of HPV infection in OSCC has been observed. We investigated HPV status, using a combination of detection methods, in a sample of 40 subjects with OSCC coded by the latest site classifications. Moreover, we performed a critical review of the studies with the same outcomes. The main finding of our investigation was a low frequency of HPV-positive OSCC, suggesting no significant HPV role in strictly oral carcinogenesis.The aim of this study was to evaluate HPV status in oral squamous cell carcinoma (OSCC), as coded by the latest classifications and applying a combination of detection methods used in clinical practice. Forty-two patients with suspect OSCC were consecutively recruited. Patients underwent an incisional biopsy for histological OSCC diagnosis and HPV identification by PCR DNA and p16 IHC. All lesions were coded by the latest ICD-0-3.2 site/histology classifications, as proposed for OSCC by the National Cancer Institute Surveillance, Epidemiology and End Results Programs. Moreover, a comparative analysis review, critically evaluated by the same site-coded systems and HPV detection methods, was performed. In 40 confirmed cases of OSCC, the frequency of HPV infection was 10% (4/40). Among positive patients, two cases were PCR DNA/p16 IHC positive (high-risk HPV 51, high-risk HPV 67), two cases were PCR DNA positive/p16 IHC negative (high-risk HPV 31 + 68, high-risk HPV 66). Applying the latest site coding systems for OSCC, the frequency of HPV infection in this study and in similar, reviewed investigations was low (from 3.3% to 12.5%). These results suggested no significant HPV role in oral carcinogenesis, particularly where an updated site-coded classification of OSCCs (categorically excluding the base of the tongue) had been performed.

Diagnostic Accuracy of HPV Detection in Patients with Oropharyngeal Squamous Cell Carcinomas: A Systematic Review and Meta-Analysis.

The aim of the study was to evaluate the diagnostic accuracy of Human Papillomavirus (HPV) techniques in oropharyngeal cancer. PubMed, EMBASE, the Cochrane Library and clinicaltrials.org were systematically searched for studies reporting methods of HPV detection. Primary outcomes were sensitivity and specificity of HPV detection. In this case, 27 studies were included (n = 5488, 41.6% HPV+). In this case, 13 studies evaluated HPV detection in tumour tissue, nine studies examined HPV detection in blood samples and five studies evaluated HPV detection in oral samples. Accuracy of HPV detection in tumour tissue was high for all detection methods, with pooled sensitivity ranging from 81.1% (95% CI 71.9–87.8) to 93.1% (95% CI 87.4–96.4) and specificity ranging from 81.1% (95% CI 71.9–87.8) to 94.9% (95% CI 79.1–98.9) depending on detection methods. Overall accuracy of HPV detection in blood samples revealed a sensitivity of 81.4% (95% CI 62.9–91.9) and a specificity of 94.8% (95% CI 91.4–96.9). In oral samples pooled sensitivity and specificity were lower (77.0% (95% CI 68.8–83.6) and 74.0% (95% CI 58.0–85.4)). In conclusion, we found an overall high accuracy for HPV detection in tumour tissue regardless of the HPV detection method used. HPV detection in blood samples may provide a promising new way of HPV detection.

HPV in the malignant transformation of sinonasal inverted papillomas: A meta-analysis.

To date, there is still a significant debate on the role of human papilloma virus (HPV) infection in transformation of inverted papillomas (IPs) to squamous cell carcinoma (SCC). This study was designed to determine if the presence of HPV in a sinonasal IP increases the risk of malignant transformation to IPSCC. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 19 high-quality case-control and cohort studies with tissue-diagnosed IP or IPSCC and HPV diagnosis were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method with correction for random effects. Subgroup, publication bias and a sensitivity analyses were also performed. Nineteen studies with minimal bias met the inclusion criteria for quality and identified HPV infection in an IP. The pooled data revealed a strong association with progression to malignancy with an unweighted, pooled OR of 2.38 (CI95 1.47 to 3.83) and a weighted OR of 2.80 (CI95 1.42 to 5.51). Sensitivity analysis revealed that no single study contributed significantly to our pooled OR calculations (ORs 2.52 to 3.57). Subgroup analyses stratified by publication date, nucleic acid target, HPV detection method and type, sample size, and region all demonstrated a positive association of HPV with IPSCC. There appears to be a significant association between HPV infection and malignant transformation of IPs. While HPV testing is not currently the standard of care for IPs, these data suggest a link between the two and suggest further studies should be performed to identify a link between the virus and malignant transformation.

Human Papillomavirus in Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Simple SummaryThe causative role of human papillomavirus (HPV) in sinonasal squamous cell carcinoma (SNSCC) remains unclear and is hindered by small studies using variable HPV detection techniques. This meta-analysis aims to provide an updated overview of HPV prevalence in SNSCC stratified by detection method, anatomic subsite, and geographic region. From 60 eligible studies, an overall HPV prevalence was estimated at 26%. When stratified by detection method, HPV prevalence was lower when using multiple substrate testing compared to single substrate testing. Anatomic subsite HPV prevalence was higher in subsites with high exposure to secretion flow compared to low exposure subsites. HPV prevalence in SNSCC followed the global distribution of HPV+ oropharyngeal squamous cell carcinoma. Taken together, this meta-analysis further supports a role for HPV in a subset of SNSCCs.Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting evidence suggests HPV is also involved in a subset of sinonasal squamous cell carcinomas (SNSCC), yet small sample sizes and variability of HPV detection techniques in existing literature hinder definitive conclusions. A systematic review was performed by searching literature through March 29th 2020 using PubMed, Embase, and Web of Science Core Collection databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed by two authors independently. A meta-analysis was performed using the random-effects model. Sixty studies (n = 1449) were eligible for statistical analysis estimating an overall HPV prevalence of 25.5% (95% CI 20.7–31.0). When stratified by HPV detection method, prevalence with multiple substrate testing (20.5%, 95% CI 14.5–28.2) was lower than with single substrate testing (31.7%, 95% CI 23.6–41.1), highest in high-exposure anatomic subsites (nasal cavity and ethmoids) (37.6%, 95% CI 26.5–50.2) vs. low-exposure (15.1%, 95% CI 7.3–28.6) and highest in high HPV+ OPSCC prevalence geographic regions (North America) (30.9%, 95% CI 21.9–41.5) vs. low (Africa) (13.1, 95% CI 6.5–24.5)). While small sample sizes and variability in data cloud firm conclusions, here, we provide a new reference point prevalence for HPV in SNSCC along with orthogonal data supporting a causative role for virally driven tumorigenesis, including that HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ OPSCC is more prevalent.

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma.

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.

In situ hybridization for high risk HPV E6/E7 mRNA in oropharyngeal squamous cell carcinoma.

To report a single institution's experience using human papillomavirus (HPV) E6/E7 mRNA in-situ hybridization (mRNA ISH) for HPV detection in oropharyngeal squamous cell carcinoma (OPSCC). To review the literature on HPV detection methods. Retrospective chart review, literature review. Tertiary care academic hospital. We conducted a retrospective chart review of 122 OPSCC biopsy specimens. mRNA ISH was performed on formalin-fixed paraffin-embedded (FFPE) tissue with a pool of 18 high risk HPV probes using an automated stainer; p16 immunohistochemistry (IHC) was also performed. We conducted a literature review on HPV detection methods including p16 IHC, mRNA ISH, DNA ISH, and PCR. In our cohort, mRNA ISH had a sensitivity and specificity of 100% and 100% with reference to p16 (100% concordance). 2-year OS was 87.5% vs. 94.5% for p16/HPV-negative vs. positive patients. 2-year DFS was 60.0% vs. 84.2%. On literature review, mRNA ISH demonstrated consistently high sensitivity and specificity ranging from 88-98% and 90-100% respectively. In comparison, the specificity of p16 was 85-95%. Our report supports the use of mRNA ISH for HPV detection in OPSCC and validates its feasibility using automated tissue staining methods on FFPE tissue. Our findings and literature review support that mRNA ISH may have superior specificity and be easier to interpret than p16. Further study on the prognostic value and cost-effectiveness of mRNA ISH is warranted and may establish this HPV detection method as the "gold standard."

Distribution of HPV Genotypes in Patients with a Diagnosis of Anal Cancer in an Italian Region.

Objectives: Anal cancer is a rare disease. However, its incidence is increasing in some population groups. Infection caused by Human Papillomavirus (HPV) is strongly associated with the risk of anal cancer, whose variability depends on samples, histology, and HPV detection methods. The aim of the study was to assess prevalence and distribution of HPV genotypes in patients diagnosed with anal carcinoma. Methods: An observational, retrospective study was carried out in a tertiary care hospital in North Sardinia, Italy. Specimens of anal cancer diagnosed from 2002–2018 were selected. Demographic, epidemiological, and clinical variables were collected to assess their relationship with the occurrence of anal cancer. Results: The overall HPV positivity was 70.0% (21/30), with HPV-16 being the predominant genotype (~85%). The highest prevalence of anal cancer was in patients aged ≥55 years. HPV positivity was higher in women (p-value > 0.05) and in moderately differentiated samples (G2) (p-value < 0.05). p16INK4a and E6-transcript positivity were found in 57% and 24% of the HPV positive samples, respectively. The OS (overall survival) showed a not statistically significant difference in prognosis between HPV positive sand negatives (10, 47.6%, vs. 4, 44.4%; p-value = 0.25). Conclusions: HPV-DNA and p16INK4a positivity confirmed the role of HPV in anal carcinoma. Our findings could support the implementation and scale-up of HPV vaccination in males and females to decrease the incidence of HPV-associated cancers. Further studies are needed to better clarify the prognostic role of HPV/p16 status.

Prevalence of human papillomavirus in oral gargles and tonsillar washings

Human papillomavirus (HPV) infection drives carcinogenesis in the oropharynx. No standard sampling or HPV detection methods for evaluating oropharyngeal HPV infection exist. The prevalence of oral HPV infection in Japan is unknown. We examined 435 healthy Japanese individuals to address whether adding tonsillar washing to oral gargling would improve HPV detection. We compared HPV assessment using GENOSEARCH HPV31 versus nested PCR and direct sequencing. Associations between HPV infection and demographic and behavioral characteristics were examined. Most participants who were HPV-positive based on oral gargles were also HPV-positive based on tonsillar washings: 11 (64.7%) of 17 on nested PCR and 12 (70.6%) of 17 on GENOSEARCH HPV31. Although HPV infection was more prevalent in oral gargles followed by tonsillar washings than in oral gargles alone, the difference was not statistically significant (nested PCR, 4.8% vs. 3.9%, P=0.46; GENOSEARCH HPV31, 5.3% vs. 3.9%, P=0.33). The overall agreement between nested PCR and GENOSEARCH HPV31 was 98.6%, with 76.0% positive agreement. The overall prevalence of oral HPV infection in Japan was 5.7% (95% confidence interval, 3.9-8.3%). Men had a significantly higher prevalence of oral HPV infection than women (8.3% vs. 2.6%, P=0.02). Infection increased with number of lifetime sexual partners (P<0.001 for trend). The oropharynx is probably the major source of HPV-infected cells in oral gargles. Oral gargling could be a standard sampling method for evaluating oropharyngeal HPV infection. GENOSEARCH HPV31 could be an option for oral HPV detection.

Molecular Diagnostics in Human Papillomavirus-Related Head and Neck Squamous Cell Carcinoma.

The incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma continues to increase. Accurate diagnosis of the HPV status of a tumor is vital, as HPV+ versus HPV– tumors represent two unique biological and clinical entities with different treatment strategies. High-risk HPV subtypes encode oncoproteins E6 and E7 that disrupt cellular senescence and ultimately drive tumorigenesis. Current methods for detection of HPV take advantage of this established oncogenic pathway and detect HPV at various biological stages. This review article provides an overview of the existing technologies employed for the detection of HPV and their current or potential future role in management and prognostication.

Development and Validation of a Novel and Rapid Molecular Detection Method for High-Risk Human Papillomavirus in Formalin-Fixed, Paraffin-Embedded Tumor Tissue

The most widely applied algorithm for human papillomavirus (HPV) detection in formalin-fixed, paraffin-embedded (FFPE) specimens of oropharyngeal head and neck squamous cell carcinoma (HNSCC) consists of p16INK4A immunostaining followed by PCR-based detection of high-risk HPV DNA on p16INK4A-immunopositive samples. However, in nonoropharyngeal HNSCC this algorithm fails, hampering correct interpretation of the prevalence and prognosis of HPV in these cases. In this study, we developed and validated a molecular HPV detection method for FFPE specimens of oropharyngeal and nonoropharyngeal HNSCC. Sectioning of FFPE blocks was circumvented by using punch biopsies from tumor-enriched regions of FFPE tissue blocks, and combined extraction was applied to obtain high-quality DNA and RNA from the punch biopsy. Next, PCR-based detection of HPV DNA was performed for 15 high-risk HPV types with subsequent detection of E6 mRNA for validation. The combined DNA/RNA FFPE test of tissue cores was assessed in well-characterized cohorts with known HPV status based on earlier work, that is, a cohort of oropharyngeal HNSCC (n = 80) and oral cavity HNSCC (n = 25), and reached an accuracy of 97% and 100%, respectively. In conclusion, our method is rapid, simple, and shows an excellent diagnostic performance for detection of HPV type 16. Ultimately, it can be applied for large cohort studies to determine the etiologic fraction and prognostic implication of HPV in nonoropharyngeal HNSCC.

Current Perspective on HPV-Associated Oropharyngeal Carcinomas and the Role of p16 as a Surrogate Marker of High-Risk HPV

The incidence of oropharyngeal carcinomas associated with human papillomavirus (HPV) is continuously increasing. HPV-positive and -negative oropharyngeal carcinomas have different epidemiological, clinical, and molecular features, with HPV-positive tumors having a better response to treatment and better prognosis. An adequate staging system for HPV-related oropharyngeal carcinomas is needed, as the American Joint Committee on Cancer 7th Edition did not consider their unique biological behavior. At present, oropharyngeal carcinomas are subdivided into p16 positive and p16 negative tumors, based on their expression of p16, a surrogate marker of high-risk HPV. This review summarizes current knowledge of HPV-associated oropharyngeal carcinomas with emphasis on their molecular features and histopathology, as well as summarizes and compares HPV detection methods and genotyping techniques. This review also describes the prognostic significance of p16 expression in these tumors and significant changes in the staging of oropharyngeal carcinomas based on p16 expression, together with the justifications for these changes. Finally, this review reports the recommendations of the College of American Pathologists for testing HPV in head and neck cancers, supported by the American Society of Clinical Oncology. This work was supported by the Ministry of Health of the Czech Republic, grant No. 15-31627A. All rights reserved. Auto&#345;i deklarují, &#382;e v souvislosti s p&#345;edm&#283;tem studie nemají &#382;ádné komer&#269;ní zájmy. Redak&#269;ní rada potvrzuje, &#382;e rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských &#269;asopis&#367;. Submitted: 18. 2. 2019 Accepted: 30. 5. 2019.

Pap smear screening for a sample of female patients with anogenital

Background and objective: Genital human papillomavirus (HPV) infection is closely linked to cancer of the cervix. The Papanicolaou-stained smear is the primary method for detection of high-risk HPV. This study aimed to identify women at risk of developing cervical precancerous lesions. Methods: This cross-sectional study involved 75 married, non-pregnant women with anogenital warts. Sociodemographic, fertility history, and details of the anogenital wart infection were obtained from all patients through a questionnaire. Pap smear was performed for all patients, and histopathological assessment was done. Results: The age of the patients ranged from 18 to 55 years. The mean (± SD) age of marriage was 22.2 (± 5.77) years, 12 (16%) women gave birth to a child before the age of 18 years. Filiform warts were identified in 33 (44%) patients, while the acuminate type was found in 24 (32%) patients. Flat warts were seen in nine (12%) patients. There was a significant association between the type of wart and recurrence. Severe erosive cervicitis was found in 45 (60%) smears. Moderate cervicitis was observed in 24 (32%) smears, and six (8%) had mild cervicitis. A significant association was found between duration of the genital wart and cervicitis. Twenty percent had atypical squamous cells of undetermined significance. No malignant changes and no koilocytes were identified. Conclusion: Early marriage, unawareness of the risk of anogenital warts, and neglecting regular Pap smears are risk factors for developing cervical cancer.

Comparison of urine, self-collected vaginal swab, and cervical swab samples for detecting human papillomavirus (HPV) with Roche Cobas HPV, Anyplex II HPV, and RealTime HR-S HPV assay

BackgroundHuman papillomavirus (HPV) is well established as the main cause of cervical cancer. Non-invasive self-collected urine and vaginal sampling have the potential advantage of increasing patient compliance with cervical cancer screening. MethodsSelf-collected vaginal and urine samples and clinician-collected cervical samples were collected from 101 patients, including 84 patients with high grade squamous intraepithelial lesion and 17 patients with benign ovarian disease. Each sample was evaluated with RealTime HR-S HPV, Anyplex™ II HPV, and Cobas® HPV assays. The concordance of urine and of self-collected vaginal samples with cervical samples was assessed using the kappa (k) statistic. ResultsIn any high-risk HPV (hrHPV), the concordance of self-collected vaginal and urine samples compared to cervical samples was moderate (k 0.49–0.58) and fair to moderate (k 0.33–0.51), respectively. In HPV 16/18, the concordance of vaginal and urine samples compared to cervical samples was almost perfect (k 0.81–0.86) and moderate to substantial (k 0.59–0.63), respectively. Among the three methods for HPV detection, RealTime HR-S showed the highest concordance with vaginal (k: any hrHPV 0.58, HPV 16/18 0.86) and urine samples (k: any hrHPV 0.51, HPV 16/18 0.63) compared to cervical samples. ConclusionHPV tests using self-collected vaginal samples and urine showed substantial and moderate agreement compared with cervical samples, respectively, although HPV tests using these samples were still inferior to clinician-collected cervical samples. Further research is needed on the clinical performance of HPV testing using urine and self-collected vaginal samples as the screening method.

Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina.

We estimated the overall and type-specific prevalence of human papillomavirus (HPV) and p16 overexpression in vaginal cancer and vaginal intraepithelial neoplasia (VaIN). We conducted a systematic search of PubMed, Embase and Cochrane Library to identify studies published between 1986 and 2017 using PCR-based or Hybrid Capture 2 tests to evaluate the presence of HPV DNA and/or using any method to detect p16 overexpression in VaIN, vaginal squamous cell carcinoma (VaSCC), or other types of vaginal cancer. Applying a random effects model, we estimated the pooled prevalence of HPV and p16 overexpression along with 95% confidence intervals (CIs). The I2 statistic was used to assess heterogeneity. We included 26 studies, reporting HPV prevalence and six studies evaluating p16 overexpression. The pooled HPV prevalences in VaSCC (n = 593) and VaIN (n = 1,374) were 66.7% (95% CI = 54.7-77.8) and 85.2% (95% CI = 78.2-91.0), respectively. Substantial inter-study heterogeneity was observed, and analyses stratified on geographic region, type of tissue, HPV detection method or PCR primer type did not fully explain the observed heterogeneity. The most predominant HPV type among the HPV positive VaSCC and VaIN cases was HPV16, followed by HPV33, and HPV45 (in VaIN) and HPV18, and HPV33 (in VaSCC). In pooled analyses, 89.9% (95% CI = 81.7-94.6) of HPV positive and 38.9% (95% CI = 0.9-90.0) of HPV negative vaginal cancers were positive for p16 overexpression. Our findings suggest that vaccination against HPV might prevent a substantial proportion of vaginal neoplasia and highlight the need for further studies of the possible clinical value of p16 testing in these patients.

Effect of HPV Infection on the Occurrence and Development of Laryngeal Cancer: A Review.

Laryngeal cancer has the second highest incidence of head and neck malignant tumors worldwide. In recent years, studies have shown that human papillomavirus (HPV) infection may be a high-risk factor for laryngeal cancer and closely related to the development and prognosis of laryngeal cancer. The mechanism of the occurrence and development of laryngeal cancer caused by HPV infection needs investigation, as does a rapid and effective HPV detection method for effectively preventing the occurrence of laryngeal cancer and controlling its development. Many studies have explored the relation between HPV infection and laryngeal cancer. Here we review the research progress in investigating HPV infection in terms of DNA, mRNA and protein levels in the occurrence and development of laryngeal cancer and routine HPV detection methods.

Preference of specimen collection methods for human papillomavirus detection for cervical cancer screening: a cross-sectional study of high-risk women in Mombasa, Kenya

Preference of specimen collection methods for human papillomavirus detection for cervical cancer screening: a cross-sectional study of high-risk women in Mombasa, Kenya

Preference of specimen collection methods for human papillomavirus detection for cervical cancer screening: a cross-sectional study of high-risk women in Mombasa, Kenya

ObjectivesSelf-collection of genital specimens for high-risk types of human papillomavirus (hrHPV) detection may increase cervical cancer screening uptake. We hypothesized that women would prefer self-collection to clinician-collection of genital specimens. To test this hypothesis, and women’s preference between two different self-collection approaches, a total of 199 women were enrolled in a cross-sectional study in Mombasa, Kenya.Materials and methodsParticipants provided self-collected specimens using the Evalyn cytobrush (Rovers) stored in a dry tube and the Viba cytobrush (Rovers) stored in wet Aptima media (Hologic). A clinician also collected cervical specimens for hrHPV testing and for cytology, and performed visual inspection using acetic acid. A post-examination questionnaire assessed preferences for the different methods of specimen collection. To test the difference in proportions for each collection method, we performed an exact binomial probability test, under the null hypothesis that women would prefer each specimen-collection method equally.ResultsMost women preferred clinician-collection over self-collection (68% versus 32%, p < 0.01). For self-collection, dry-self collection with the Evalyn brush was preferred over the wet-selection with the Viba brush (53% versus 27%, p < 0.01). There was no association between preference for self-collection and preference for a particular self-collection cytobrush.ConclusionFurther research to understand and address obstacles to self-collection of genital specimens may be needed to improve the uptake of self-collection for cervical cancer screening, especially in settings with poor access to trained healthcare providers.

Detection of HPV infection in head and neck cancers: Promise and pitfalls in the last ten years: A meta-analysis.

The current controversial discussion on the disease-specific survival of patients with human papillomavirus (HPV)-positive (+) and -negative (−) squamous cell carcinoma (SCC) of the head neck region was the motivation for the present meta-analysis. Different detection methods for HPV are available, though these often lack sensitivity. As a consequence, there may be false interpretation of HPV positivity. A bias concerning HPV status and therefore also survival rates is serving a non-durable relevance in the discussion of tailored therapies. A literature search was performed via the online database PubMed/NCBI, and data extraction and statistical analysis were conducted. A total of 139 studies published between 2004 and 2014 were evaluated in the present meta-analysis. The HPV detection methods, patient characteristics, tumor localizations and stages, as well as (neo-) adjuvant therapies and survival times were analyzed. The average incidence rates of HPV+ patients with oropharyngeal tumors were higher than those of patients with cancers of other regions of the head and neck. Upon evaluating the results of different detection methods no significant differences were identified. We have compared the HPV incidence rates of each detection method, when studies have used more than one. Regarding overall survival, the pooled adjusted hazard ratio (HR) for oropharyngeal SCC was 0.31 [95% confidence interval (CI)=0.27–0.36]. Unfortunately, only 3 equivalent studies were available on nonoropharyngeal tumors, for which the pooled adjusted HR was 1 (95% CI=0.73–1.36). Overall, the evaluation demonstrated that the survival rates reported in numerous studies were not evaluated multifactorially and important confounders were excluded from the statistics. The HPV detection methods used were often not sufficient in representing HPV positivity. In addition, oropharyngeal and oral SCCs were assessed together in the localization. The widely differing number of HPV+ patients in each of the various studies may be explained by insufficient detection methods and by a lack of localization distinction. The considerations of a tailored therapy according to HPV status should be rejected based on the present information. The previously published studies should be read critically and do not represent a basis for therapeutic decisions.

HPV genotype distribution among women with normal and abnormal cervical cytology presenting in a tertiary gynecology referral Clinic in Ethiopia

BackgroundCervical cancer is the second most prevalent cancer among women of child-bearing age in Ethiopia. The aim of this study was to determine human papilloma virus (HPV) genotype distribution among HIV-negative women with normal and abnormal cervical cytology results.MethodsWe investigated a consecutive of 233 HIV-negative women between December 2008 and March 2009 presenting in a Tertiary Gynecology Referral Clinic in Ethiopia. Screening was done by Pap cytology and HPV detection and genotyping method was nested PCR (direct amplification with MY09/MY11 primers, followed by nested amplification with GP5/GP6 primers) and sequencing of the nested products. Sequencing of the non-purified nested PCR products was performed following re-amplification with Big dye terminator, using the GP6 primer.ResultsOf the 233 study participants, 92 (39.5%) had abnormal cytology. All women with abnormal cervical cytology had positive HPV DNA compared to only 48.9% of those presenting with normal cytology. Of these women, the frequency of high-risk (HR)-HPV was 83.2% and its prevalence in women with abnormal cervical cytology was significantly higher than those with normal cytology (92.4% vs. 71%, p < 0.0001). The most frequent genotypes identified were HPV16 (44.1%), followed by HPV35 and HPV45 (each 6.2%), HPV31 (4.4%), HPV56 (3.7%), HPV18 and HPV59 (each 3.1%), HPV58 (2.5%) and HPV39 (1.9%). While the most common HR-HPV infections among women with normal cytology were HPV16 (20.3%), followed by HPV35 (8.7%), HPV56 and HPV58 (each 5.8%), HPV18, HPV31 and HPV39 (each 4.4%), HPV45 (2.9%) and HPV59 and HPV68 (each 1.5%), the most common HR-HPV infections in women with abnormal cytology included HPV16 (62%), followed by HPV45 (8.7%), HPV 31, HPV35 and HPV59 (each 4.4%), and HPV18, HPV52 and HPV56 (each 2.2%). We also noted low prevalence of multiple HPV infections in women with normal or abnormal cytology. Multivariable logistic analysis showed that residing in rural area (OR 3.24, 95% CI: 1.13–9.30), being multipara (OR 7.35, 95% CI: 1.78–30.38) and having abnormal cervical cytology results (OR 6.75, 95% CI: 1.78–25.57) were all independently associated with HPV16 genotype.ConclusionsOur study revealed a significant risk of infection with HR-HPV, in particular with HPV16 genotype, in women attending a referral center in Ethiopian women presenting with or without abnormal cervical cytology. Moreover, Pap smear cytology missed a significant proportion of women compared to those who were identified by PCR for HR-HPV infections. In addition, the PCR method we used was not suitable for sensitive detection of co-existent multiple infections. Data from the present study indicate that currently available HPV vaccines could prevent nearly 67% of all cervical cancer cases in women in Ethiopia.

Validation of a new HPV self-sampling device for cervical cancer screening: The Cervical and Self-Sample In Screening (CASSIS) study

ObjectiveWe compared the self-sampling performance of the newly designed HerSwab™ device with a physician-collected cervical sample and another self-sample using the cobas® PCR Female swab for the detection of cervical intraepithelial neoplasia (CIN) and cancer. MethodsWomen referred for colposcopy at McGill University affiliated hospital clinics collected two consecutive self-samples, one with HerSwab™ and one with cobas® swab, after receiving instructions. The order of sampling was randomized. The colposcopist then collected a cervical sample and conducted a colposcopic examination. Samples were tested for human papillomavirus (HPV) DNA. Sensitivity and specificity to detect CIN2+ and respective 95% confidence intervals (CI) were calculated to compare sampling approaches. The HPV testing agreement between samples was measured using the Kappa statistic. ResultsOf 1217 women enrolled, 1076 had complete results for HPV and cytology; 148 (13.8%) had CIN1, 147 (13.7%) had CIN2/3, and 5 (0.5%) had cancer. There was very good agreement between methods for HPV detection (HerSwab™ versus physician: kappa=0.84; cobas® swabs versus physician: kappa=0.81; HerSwab™ versus cobas® swabs: kappa=0.87). The sensitivity of HPV detection for CIN2+ was 87.6% (95%CI: 79.8–93.2) with self-sampling using HerSwab™, 88.6% (95%CI: 80.9–94.0) with self-sampling using the cobas® swab, and 92.4% (95%CI: 85.5–96.7) with physician sampling. Corresponding estimates of specificity were 58.1% (95%CI: 54.1–62.1), 55.0% (95%CI: 50.9–59.0) and 58.7% (95%CI: 54.6–62.6). Cytology (ASC-US or more severe) done on the physician-collected specimen was 80.2% (95%CI: 70.8–87.6) sensitive and 61.4% (95%CI: 57.2–65.5) specific for CIN2+. ConclusionsThe HerSwab™ had good agreement with physician sampling in detecting HPV, and adequate performance in detecting high-grade lesions among women referred to colposcopy for abnormal cytology.