Detection of viral gene expression in risk-stratified biopsies reveals no active HPV in cutaneous squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) infection is known to promote the development of mucosal squamous cell carcinoma (mSCC), including pathologically high-grade lesions, but its role in cutaneous squamous cell carcinoma (cuSCC) remains unclear, particularly in lesions that are considered high risk. OBJECTIVE: We aimed to determine whether enhanced HPV transcriptional activity can be detected in high-risk cuSCC samples compared with low-grade SCC samples or normal skin. METHODS: We performed RNA sequencing of cuSCC across 23 risk-stratified skin lesions. A subset of samples was tested for the presence of HPV DNA. High-quality, non-human reads from each sample group were used for viral analysis using Microbiome Coverage Profiler. RESULTS: None of the samples analysed had detectable expression of HPV RNA, while 64% of samples tested positive for HPV DNA. All samples were found to have expression of human endogenous retrovirus, and multiple samples showed expression of other viruses. CONCLUSIONS: Viral and prophage gene expression can be monitored in cuSCC or normal skin biopsies, yet no sample in our study showed evidence of active HPV gene expression despite evidence of HPV genome presence. This suggests HPV transcription does not play a role in differentiating high-risk cuSCCs from low-risk cuSCCs or normal skin.

Anal Cancer Precursor Lesions in HIV-Infected Persons: Tissue Human Papillomavirus Type Distribution and Impact on Treatment Response.

BACKGROUND: Data on tissue distribution of human papillomavirus types in anal high-grade squamous intraepithelial lesions are limited and the impact on treatment outcomes poorly understood. OBJECTIVE: We aimed to investigate potential predictors of treatment failure after electrocautery ablation, including human papillomavirus type(s) isolated from index lesions. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a tertiary academic referral center in New York City. PATIENTS: Seventy-nine HIV-infected patients with a diagnosis of anal high-grade squamous intraepithelial lesions between January 2009 and December 2012 were included, and genomic DNA was extracted from biopsy tissue. MAIN OUTCOME MEASURES: The prevalence of human papillomavirus types in index lesions and surveillance biopsies after electrocautery ablation were analyzed to evaluate treatment response. RESULTS: Of 79 anal high-grade squamous intraepithelial lesions, 71 (90%) tested positive for ≥1 human papillomavirus type; 8 (10%) had no human papillomavirus detected. The most common type was 16 (39%), followed by 33 (15%). Human papillomavirus type 18 was seen in 3%. Sixty-one patients (77%) underwent electrocautery ablation and had subsequent surveillance biopsies. Surveillance biopsies yielded benign findings or low-grade squamous intraepithelial lesions in 31 (51%) of 61 and recurrent high-grade squamous intraepithelial lesions in 30 (49%) of 61 patients (mean follow-up: 35 mo). Ablation response did not differ significantly based on baseline demographics, smoking history, history of anogenital warts, mean CD4 T-cell count, antiretroviral-therapy use, and HIV viral load (<50 copies/mL). The recurrence of high-grade lesions was not significantly associated with high-risk human papillomavirus types detected in index lesions. LIMITATIONS: Human papillomavirus genotyping in surveillance biopsies was not performed. CONCLUSIONS: Anal high-grade squamous intraepithelial lesions in HIV-infected patients contain a wide range of human papillomavirus types, and individual lesions commonly harbor multiple types concomitantly. Recurrence of anal high-grade squamous intraepithelial lesions after electrocautery ablation occurs frequently and is not affected by high-risk human papillomavirus types. See Video Abstract at http://links.lww.com/DCR/A833.

Correlation between integration of high-risk HPV genome into human DNA detected by molecular combing and the severity of cervical lesions: first results of the EXPL-HPV-002 study.

OBJECTIVES: The aim of the EXPL-HPV-002 study is to evaluate the integration of 14 high-risk HPV as a biomarker of the severity and the progression of cervical lesions. Such a „triage biomarker“ would help to reduce the number of unnecessary colposcopies, to avoid over-treatment of lesions that spontaneously regress and to better target the lesions requiring treatment. DESIGN: EXPL-HPV-002 is a prospective, open-label, single arm, GCP study conducted at 2 clinical sites in the Czech Republic. SETTINGS: Investigations centers: Private Gynecology Center, Brno; Gynecological and Obstetrical Clinic, Brno; Genotyping central lab: NRL for Papillomaviruses and polyomaviruses, IHBT, Prague; Histology Central reading: Aeskulab Pathology, Prague; Molecular combing HPV test: Genomic Vision, Bagneux. METHODS: From June 2016 to May 2018, 688 patients aged 25-65, referred to colposcopy after an abnormal Pap-smear, were enrolled in the study. Among them 60% were found HPV high-risk. The study is divided in two phases: 1. a cross-sectional phase using data collected at first visit (colposcopy images ± histology, pap-smear for HPV genotyping and molecular combing) to study the association between HPV integration status versus colposcopy and histology grades; 2. a longitudinal phase using data collected in follow-up visits: cytology at 6, 18 and 30 months and colposcopy ± histology at 12, 24 and 36 months. A pap-smear collected at 12, 24 and 36 months allows to perform genotyping and molecular combing. HPV integration status is analyzed in comparison with the evolution of lesions, viral clearance and HPV genotype. HPV genotyping and molecular combing were performed on pap-smear samples in central laboratories. Histology data were reviewed by central reading. RESULTS: The transversal phase of the study is achieved and shows that the HPV integration into the human DNA, monitored by molecular combing, can significantly differentiate normal subjects from women with cervical lesions or cancer. CONCLUSION: HPV integration into the host genome, monitored by Genomic Visions technology, is a reliable diagnostic biomarker that will greatly help clinicians to improve their medical decision tree.

Performance of a new HPV and biomarker assay in the management of hrHPV positive women: Subanalysis of the ongoing multicenter TRACE clinical trial (n > 6,000) to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer.

The ongoing Triage and Risk Assessment of Cervical Precancer by Epigenetic Biomarker (TRACE) prospective, multicenter study aimed to provide a clinical evaluation of the CONFIDENCE™ assay, which comprises a human papillomavirus (HPV) DNA and a human epigenetic biomarker test. Between 2013 and 2015 over 6,000 women aged 18 or older were recruited in Hungary. Liquid-based cytology (LBC), high-risk HPV (hrHPV) DNA detection and single target host gene methylation test of the promoter sequence of the POU4F3 gene by quantitative methylation-specific polymerase chain reaction (PCR) were performed from the same liquid-based cytology sample. The current analysis is focused on the baseline cross-sectional clinical results of 5,384 LBC samples collected from subjects aged 25 years or older. The performance of the CONFIDENCE HPV™ test was found to be comparable to the cobas® HPV test with good agreement. When applying the CONFIDENCE Marker™ test alone in hrHPV positives, it showed significantly higher sensitivity with matching specificity compared to LBC-based triage. For CIN3+ histological endpoint in the age group of 25-65 and 30-65, the methylation test of POU4F3 achieved relative sensitivities of 1.74 (95% CI: 1.25-2.33) and 1.64 (95% CI: 1.08-2.27), respectively, after verification bias adjustment. On the basis of our findings, POU4F3 methylation as a triage test of hrHPV positives appears to be a noteworthy method. We can reasonably assume that its quantitative nature offers the potential for a more objective and discriminative risk assessment tool in the prevention and diagnostics of high-grade cervical intraepithelial neoplasia (CIN) lesions and cervical cancer.

Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence.

BACKGROUND: The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness. PATIENTS AND METHODS: A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival. RESULTS: HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7-70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ・} 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008-0.6, p = 0.009). CONCLUSION: In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment.

Excellent analytical and clinical performance of a dry self-sampling device for human papillomavirus detection in an urban Chinese referral population.

AIM: To evaluate the analytical and clinical effectiveness of cervicovaginal self-sampling with a dry sampling device (Evalyn Brush) for high-risk human papillomavirus (hr-HPV) testing and detection of cervical disease. METHODS: The study population consisted of 101 patients from a large gynecological outpatient clinic in Shanghai referred for abnormal cervical screening results and 101 women without cervical lesions. Self-samples obtained in the clinic and physician-collected cervical specimens (reference) were stored at -20 °C for 16-18 weeks and then transferred to 20 ml of ThinPrep medium and tested for hr-HPV using a multiplex real time polymerase chain reaction assay. All women had a colposcopic examination with a Pap smear and directed or random biopsies. RESULTS: High risk-HPV was detected in 92 patients (45.5%) with the self-collected cervicovaginal specimens and in 93 (46.0%) with the physician-collected cervical specimens, resulting in an agreement of 97.5% and a Kappa of 0.95 (95% confidence interval 0.91-0.99). Among all of the included women, 46 (22.8%) had cervical intraepithelial neoplasia grade 3 or worse (cervical intraepithelial neoplasia 3+). Hr-HPV was found in 43 of these patients (93.5%) with self-sampling and in 44 (95.7%) with the physician-collected specimens. CONCLUSIONS: Self-collected dry cervicovaginal samples transferred to ThinPrep medium and tested for hr-HPV using a clinically validated polymerase chain reaction assay showed very good agreement with physician-collected cervical specimens and a very high hr-HPV positivity rate for cervical intraepithelial neoplasia 3 +.

Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome.

PURPOSE: The incidence of penile cancer is increasing, and is suggested to be explained by changes in sexual practice and increased exposure of men to sexually transmitted high risk human papillomavirus infection. In penile cancers from a Dutch population treated in 1963 to 2001 we found a high risk human papillomavirus prevalence of about 30%. In this study we assessed the prevalence of high risk human papillomavirus-DNA in a more recent, contemporary penile cancer cohort and its association with patient survival. MATERIALS AND METHODS: High risk human papillomavirus-DNA presence was assessed by GP5+6+ polymerase chain reaction in 212 formalin fixed, paraffin embedded invasive penile tumor specimens of patients treated between 2001 and 2009. The 5-year disease specific survival was calculated using the Kaplan-Meier method with the log rank test and Cox regression. RESULTS: High risk human papillomavirus-DNA was detected in a subset of penile cancer cases (25%, 95% CI 19-31). HPV16 was the predominant type, representing 79% (42 of 53) of all high risk human papillomavirus infections. The 5-year disease specific survival in the high risk human papillomavirus negative group and the high risk human papillomavirus positive group was 82% and 96%, respectively (log rank test p=0.016). Adjusted for stage, grade, lymphovascular invasion and age, human papillomavirus status was still prognostic for disease specific survival (p=0.030) with a hazard ratio of 0.2 (95% CI 0.1-0.9). CONCLUSIONS: High risk human papillomavirus-DNA was observed in a quarter of penile cancer cases. No relevant increase in high risk human papillomavirus prevalence in recent decades was observed. The presence of high risk human papillomavirus-DNA in penile cancer confers a survival advantage.

Human papillomavirus prevalence and genotype distribution among HIV-infected women in Korea.

The epidemiology on human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women in Korea is not well established. A retrospective study was conducted to determine the prevalence and genotype distribution of HPV infection among HIV-infected women in Korea. HPV DNA genotype and cervical cytology were examined in 60 HIV-positive women and 1,938 HIV-negative women. HPV genotypes were analyzed by using a HPV DNA chip. HIV-infected women had higher prevalence of high-risk HPV (hr-HPV) infection (30% vs 4.9%, adjusted odds ratio [AOR], 6.96; 95% confidence interval [CI], 3.63-13.34, P<0.001) and abnormal cervical cytology (18.3% vs 1.8%, AOR, 10.94; 95% CI, 5.18-23.1, P<0.001) compared with controls. The most common hr-HPV genotype detected in HIV-infected women was HPV 16 (10%), followed by 18 (6.7%) and 52 (5%). Prevalence of quadrivalent vaccine-preventable types (HPV 6, 11, 16, and 18) was 21.7% and 2.3% in HIV-positive women and HIV-negative women, respectively. Age was a significant risk factor for hr-HPV infection in HIV-infected women (P=0.039). The presence of hr-HPV was significantly associated with abnormal cervical cytology (P<0.001). These findings suggest that HPV testing for cervical cancer screening in HIV-infected women would be necessary, particularly among young age group.

The spectrum of genital human papillomavirus infection among men attending a Swedish sexually-transmitted infections clinic: human papillomavirus typing and clinical presentation of histopathologically benign lesions.

There have been a number of Swedish studies on human papillomavirus (HPV) typing in men, most of which have used less sensitive HPV-typing techniques. The present study included male patients with genital HPV-induced lesions planned for surgery. Samples were prepared for histopathology and PCR. HPV was detected in 233/253 (92%) and HPV 6 or 11 in 89% of the HPV-positive lesions. There were statistically significant differences regarding morphology (p=0.002), location (p=0.000001) and colour (p=0.005) of the lesions for low- vs. mixed or high-risk HPV types. For example, acuminate lesions were mostly found among men with low-risk HPV types, whereas macular lesions were over-represented among them with mixed or high-risk types. The HPV type distribution is similar to that in earlier studies, but we also found correlations with some clinical parameters.

Exploring colposcopists' attitudes towards use of HPV testing as a primary screening tool for cervical cancer in British Columbia.

OBJECTIVE: To examine colposcopists' attitudes regarding human papillomavirus (HPV) DNA testing as a primary screening tool for cervical cancer. METHODS: Questionnaires administered in 2010 and 2011 during workshops in British Columbia elicited colposcopists' attitudes using a series of five-point Likert-style scales (strongly disagree to strongly agree) and binary (yes/no) response questions. The frequency of "agree" or "strongly agree" was used to characterize attitudes. Regression analyses examined statistically significant changes in attitudes after the 2010 workshop. RESULTS: Responses generally indicated positive changes in attitudes toward HPV testing. Statistically significant changes after the 2010 workshop were observed for the items relating to strong agreement that HPV is a necessary cause of cervical cancer (39% increase; P < 0.001) and the likelihood of openly advocating for HPV testing (19% increase; P < 0.04). In 2010, 40% of colposcopists stated that four years between HPV tests is too long, and in 2011, 53% did so. CONCLUSION: Colposcopists are viewed as opinion leaders and will have a critical role in implementing HPV testing in BC; our study obtained responses from 73% (2010) and 84% (2011) of BC-registered colposcopists. Colposcopists were in favour of HPV testing for primary screening for cervical cancer but did not support an extended interval for HPV testing, which suggests future knowledge translation workshops are crucial. We found that knowledge translation workshops can be an effective approach for translating evidence on screening and screening practices.

Objectif : Examiner les attitudes des colposcopistes à l'égard du dépistage de l'ADN du virus du papillome humain (VPH) à titre d'outil principal de dépistage du cancer du col utérin. Méthodes : Des questionnaires administrés en 2010 et en 2011 dans le cadre d'ateliers offerts en Colombie-Britannique se sont penchés sur les attitudes des colposcopistes au moyen de séries d'échelles en cinq points de type Likert (de « fortement en désaccord ¼ à « fortement en accord ¼) et de questions à réponse binaire (oui / non). La fréquence des réponses « en accord ¼ ou « fortement en accord ¼ a été utilisée pour caractériser les attitudes. Des analyses de régression ont examiné les modifications significatives sur le plan statistique en ce qui concerne les attitudes à la suite de l'atelier de 2010. Résultats : Les réponses ont généralement indiqué des modifications positives en ce qui concerne les attitudes envers le dépistage du VPH. À la suite de l'atelier de 2010, des modifications significatives sur le plan statistique ont été constatées pour ce qui est des articles liés au fait d'être fortement en accord avec la déclaration voulant que le VPH constitue une cause nécessaire du cancer du col utérin (hausse de 39 %; P < 0,001), ainsi que pour ce qui est de la probabilité de plaider ouvertement en faveur du dépistage du VPH (hausse de 19 %; P < 0,04). En 2010, 40 % des colposcopistes ont déclaré qu'un délai de quatre ans entre les tests de dépistage du VPH était trop long; en 2011, 53 % ont fait une telle déclaration. Conclusion : Les colposcopistes sont perçus comme étant des leaders d'opinion; ils joueront donc un rôle crucial dans la mise en œuvre du dépistage du VPH en Colombie-Britannique. Notre étude a obtenu des réponses de la part de 73 % (2010) et de 84 % (2011) des colposcopistes inscrits en C.-B. Les colposcopistes étaient en faveur de l'utilisation du dépistage du VPH aux fins du dépistage primaire du cancer du col utérin, mais ne soutenaient pas la mise en œuvre d'un intervalle prolongé dans le cadre du dépistage du VPH, ce qui semble indiquer que la tenue de futurs ateliers de transfert des connaissances s'avère cruciale. Nous avons constaté que les ateliers de transfert des connaissances peuvent constituer une approche efficace pour assurer l'application des résultats de recherche au dépistage et aux pratiques connexes.

Immunocytochemical detection of raf kinase inhibitor protein and human papillomavirus profiling of normal and abnormal cervical ThinPrep samples.

OBJECTIVES: This study investigates the potential value of Raf kinase inhibitor protein (RKIP) as a marker of normal squamous cells in ThinPrep slides. RKIP was evaluated for its ability to distinguish between normal and abnormal cervical samples in the context of human papillomavirus (HPV) infections. STUDY DESIGN: A total of 316 ThinPrep samples were taken from women with normal and abnormal cervices. ThinPrep slides were Papanicolaou stained and reported. Residual samples were used for RKIP immunostaining and HPV PCR-based sequencing. RESULTS: RKIP expression was seen in both nuclei and cytoplasm in 83.7% of samples. RKIP expression was highest (84.6%) in samples with a diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse; expression was lower in low-grade squamous intraepithelial lesions (73%) and was lowest in samples with normal cytology (p = 0.0023). A total of 74% of HPV-infected ThinPrep samples were immunopositive, and 67% of samples that did not harbor HPV were also immunopositive (p = 0.414). Sensitivity and specificity of RKIP were 84.6 and 34.6%, respectively, for the detection of samples with HSIL or worse. CONCLUSIONS: This study showed that RKIP expression may be of some value as a marker for abnormal cervical cells. Combined RKIP expression and HPV testing could improve the identification of samples with abnormal cytology.

Epidermodysplasia verruciformis associated with HPV 10.

Epidermodysplasia verruciformis (EV) is a rare, inherited dermatologic condition demonstrating an increased susceptibility to specific HPV genotypes, resulting in both benign and malignant skin lesions. Epidermodysplasia verruciformis lesions are frequently described as pityriasis versicolor-like scaly macules, flat wart-like papules, or verrucous and seborrhic keratosis-like papules and plaques. Acquired EV has been described in patients with HIV and in those who are on immunosuppressive therapy. We discuss a patient with congenital EV who presents with skin lesions associated with HPV 10, a less frequently cited causative subtype, and histological findings that are not classic for EV.

[The use of human papillomavirus genotying kit based on gene chip technology for detecting and typing of human papillomavirus].

OBJECTIVE: To evaluate a new human papillomavirus (HPV) genotyping technique based on gene chip technology (HPG) for HPV genotyping and its clinical efficacy. METHODS: HPV genotyping (HPG) test, hybrid capture II (HC2) test and DNA sequencing assay were performed in 151 patients aged 20-75 years with diagnosis of chronic cervicitis or abnormal vaginal bleeding. The cervical specimens were collected from cervical epithelium. All the cervical samples were analyzed by the HPG test, HC2 test and DNA sequencing. The clinical efficacy of the HPG test was analyzed. RESULTS: The consistent rate between HPG test and HC2 test was 87.42% (kappa = 0.75, P < 0.05). When DNA sequencing assay was regarding as the final test result, the sensitivity and specificity of HPG test for high risk HPV were 100% and 96.49%, respectively. The consistent rate between HPG test and direct DNA sequencing was 98.70% (kappa = 0.97, P < 0.05). The most common six HPV genotypes detected by HPG test were HPV 16 (13.25%), 58 (11.92%), 52 (11.92%), 31 (6.62%) 39 (5.96%), 33 (5.96%) in descending order of frequency. The incidence of multiple-types infection detected by HPG test was 23.84%. CONCLUSION: HPG test is a rapid and accurate test for HPV genotyping which could detect 29 types of HPV infection at one time. It is suitable for cervical HPV infection screening in clinic.

Incidence and prevalence of multiple types of genital human papillomavirus (HPV) infection in men: a study in Poland.

OBJECTIVES: Infections with human papillomavirus (HPV) are sexually transmitted. Their prevalence in males is comparable to females, but infection in men is largely unknown. Since such information is needed to establish prevention strategies, the goal of our study was to estimate the incidence of type-specific genital HPV infection among men in Poland. MATERIAL AND METHODS: Within a multi-center clinical preventive trial, penile sampling of 826 (100%) uncircumcised and sexually active males (aged 25-69 yrs.) was studied. Peniscopy was performed in addition to routine clinical examination. DNA HPV in smears was detected by hybrid capture (HC2) and in the biopsy material by means of polymerase chain reaction (PCR). RESULTS: Twenty-three HPV types were detected, including 11 high-risk oncogenic (53-6.4% men) and in 65 (7.87%) individuals both oncogenic and nononcogenic simultaneously--altogether 118 (14.3%) and also 12 low-risk multiple nononcogenic types (248-30% men). Penile HPV prevalence was approximately 26.8%. In 53 (6.4%) cases we detected multiple oncogenic types (single HPV16 in only 17 cases--2.1%). Penile HPV DNA was detection did not appear to be associated with age. Our analyses also suggested a lower prevalence of HPV infection among male participants who reported consistent condom use and fewer sexual partners. In men with history of having more than 10 sexual partners over their lifetime increased the likelihood of detecting HPV DNA. CONCLUSIONS: Data from our study showing a high prevalence of HPV infection in the Polish population of men will be helpful for future studies on HPV transmission dynamics.

Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study).

OBJECTIVE: New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings. To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards. STUDY DESIGN: A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3+ and CIN2+ lesions by different diagnostic tests. RESULTS: Reproducibility between the primary and second pathology reading was excellent for CIN3+ and CIN2+ endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2+ (15-20%) and CIN3+ (4-6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3+ and CIN2+ lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2+ detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2+), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%). CONCLUSIONS: These data corroborate the suitability of AHPV for the primary cervical cancer screening.

Human papillomavirus as a favorable prognostic biomarker in squamous cell carcinomas of the vagina.

OBJECTIVE: Recent evidence has confirmed two independent pathways in the development of vaginal squamous cell carcinoma (VaSCC): one related to and the other independent of human papillomavirus (HPV). The aim of our study was to evaluate whether HPV status has prognostic significance in this neoplasm. METHODS: All confirmed primary VaSCCs diagnosed and treated from 1995 to 2009 in two institutions were retrospectively evaluated (n=57). HPV infection was detected by PCR using SPF-10 primers and typed with the INNO-LIPA HPV assay and p16(INK4a) expression by immunohistochemistry. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazard's model. RESULTS: HR-HPV DNA was detected in 70.2% patients. HPV16 was the most prevalent genotype (67.5% of cases). p16(INK4a) was positive in 97.5% HPV-positive and 17.6% HPV-negative tumors (p<.001). FIGO stage was associated with DFS (p=.042) and OS (p=.008). HPV-positive tumors showed better DFS (p=.042) and OS (p=.035) than HPV-negative tumors. Multivariate analysis confirmed better DFS and OS of HPV-positive patients independent of age and stage. This reduced risk of progression and mortality in HPV-positive patients was limited to women with FIGO stages I and II tumors (HR=0.26; 95% CI 0.10-0.69; p=0.006). CONCLUSIONS: HPV-positive early stage (FIGO I and II) VaSCCs have a better prognosis than early HPV-negative tumors. HPV detection and/or p16(INK4a) immunostaining can be easily implemented in routine pathology and should be considered as valuable prognostic biomarkers in the study of patients with VaSCC.

Type-specific human papillomavirus DNA detected in atypical glandular cell Pap tests.

OBJECTIVES: To evaluate the presence of type-specific human papillomavirus (HPV) DNA in atypical glandular cells (AGCs) from cervical liquid-based cytology and to report the relationship between HPV types and cervical histological abnormalities. STUDY DESIGN: We used a nested multiplex polymerase chain reaction assay to test AGC Papanicolaou (Pap) tests for the presence of 14 high-risk (HR) HPV types. RESULTS: HR HPV types were detected in 33 of 161 AGC Pap tests (20.3%). Types 16 and/or 18 were detected in 13 samples (8%). Eight other HPV types were detected in 1-4 samples each. HPV-associated disease was diagnosed in 8 AGC cases (8%) with available histology results. The sensitivity and specificity of the HR HPV test were 87.5 and 90%, respectively, and the negative predictive value (NPV) was 99%. For a test that can isolate HPV types 16 and 18, the sensitivity and specificity were 62.5 and 100%, respectively, the positive predictive value (PPV) was 100% and the NPV was 97%. CONCLUSION: HPV 16 and 18 were the most common types detected in AGC Paps. We found high specificity, PPV and NPV with a test that can isolate these 2 HPV types. These results indicate a possible role for type-specific HPV testing in the management of AGC Pap tests.

Changing trends in human papillomavirus-associated head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) continues to be a significant disease with varying rates of incidence and mortality worldwide. Numerous studies have demonstrated that human papillomavirus (HPV) is etiologically linked with a subset of HNSCC, independent of tobacco and alcohol use. This subset of tumor shows increased sensitivity to radiation therapy and association with better outcomes. The study aims to determine the HPV burden and trend among patients with HNSCC in the southern region of the United States over the past 10 years. Of 142 cases from 2000 to 2004, 18 (13%) were positive for high-risk HPV. Nine of these were oropharyngeal tumors, including 4 cases from the tonsil. These constitute 38% (9/24) of all oropharyngeal tumors and 57% (4/7) of tonsillar tumors. Of 35 cases from 2009 to 2010, 14 (40%) were positive for high-risk HPV. Thirteen of these were oropharyngeal tumors, including 9 cases from the tonsil. These constitute 59% (13/23) of oropharyngeal tumors and 64% (9/14) of tonsillar tumors. When data from the 2 periods are combined, the results show that African American patients are less likely to have HPV-associated disease compared with white patients (9% vs 22%). Human papillomavirus-positive and oropharyngeal HNSCC are more likely to be nonkeratinizing (P < .0001). In conclusion, the HPV detection rate in oropharyngeal squamous cell carcinoma increased from 38% to 59% between the 2000-to-2004 and 2009-to-2010 periods.

Clinical and laboratorial study of HPV infection in men infected with HIV.

OBJECTIVES: To determine the prevalence of precursor lesions of penile cancer, to establish the concordance of diagnostic techniques (PCR, Hybrid Capture (HC) and peniscopy with acetic acid 5%) in the diagnosis of Human Papilloma Virus (HPV) of the penis of men infected with HIV and to evaluate the influence of the immune status. PATIENTS, METHODS AND RESULTS: 276 men were studied, with a median age of 34.6 years. Prevalence of High Risk HPV, Low Risk HPV and infection with both, according to HC, was 43%, 32% and 22%, respectively. PCR showed 50% of positivity for HPV DNA. Peniscopy was positive in 27% of individuals. Peniscopy showed good specificity and low sensitivity for the detection of penile HPV, and low concordance with PCR. Men with white lesions had a 3.6 higher relative risk of positivity for HPV. The most common clinical lesion observed was vegetation, identified in 29% of patients. PCR and HC techniques showed high sensitivity for HPV DNA and there was an excellent correlation between them. Immunosuppressed individuals with CD4 < 200 cells/mm(3) had the highest prevalence of premalignant lesions that were observed in 10% of the studied individuals. CONCLUSIONS: Peniscopy was important for identification and treatment of subclinical lesions. PCR and HC techniques were sensitive methods for the detection of HPV DNA with high concordance. Severely immunosuppressed individuals showed a higher prevalence of pre-malignant lesions of the penis.