Current oral hygiene and recreational behavioral trends in HIV disease.

OBJECTIVE: HIV disease is evolving with more HIV+ persons experiencing a high quality of life with well-controlled viremia. We recently enrolled a large cohort of HIV+ and clinically relevant HIV- persons for oral microbiome analyses that included a questionnaire related to oral hygiene and recreational behaviors. Here, the questionnaire responses were analyzed for behavioral trends within the cohort, together with trends over time by comparison to a previous geographically centered HIV+ cohort. METHODS: Data were collected by questionnaire at baseline visits as cross-sectional assessments. Multivariable analyses were conducted for associations of HIV status as well as age, race, and sex, on oral hygiene/recreational behaviors. RESULTS: HIV+ subjects had reduced brushing frequency, but increased incidence of past cleanings and frequency of dry mouth, compared to the HIV- subjects. Within the entire cohort, positive associations were identified between age and several oral hygiene practices, and between age, race, and sex for several recreational behaviors. In comparison to the historical cohort, the contemporary HIV+ cohort participated in fewer high-risk behaviors, but with similar trends for smoking and oral hygiene practices. CONCLUSION: HIV status had little association with oral hygiene and recreational behaviors despite several differences in age, race, and sex. Behavioral trends over time support a higher quality of life in people currently living with HIV.

Impact of Dietary Quality on Genital Oncogenic Human Papillomavirus Infection in Women.

BACKGROUND: Most cervical cancers are directly linked to oncogenic or high-risk human papillomavirus (HR-HPV) infection. This study evaluates associations between diet quality and genital HPV infection in women. METHODS: This study included 10 543 women from the 2003-2016 National Health and Nutrition Examination Survey. The outcome was the genital HPV infection status (HPV-negative, low-risk [LR] HPV, and HR-HPV). Dietary quality was evaluated using the Healthy Eating Index (HEI), in which a higher score indicates a better diet quality. RESULTS: Women who did not consume total fruits (15.8%), whole fruits (27.5%), or green vegetables and beans (43%) had a significantly higher risk of HR-HPV infection than women who complied with the Dietary Guidelines for Americans (HR-HPV odds ratio = 1.76, 1.63, and 1.48 for a HEI score of 0 vs 5, respectively) after adjusting confounding factors. Similar results of these food components on LR-HPV infection were found. In addition, intake of whole grains and dairy was inversely associated with LR-HPV infection. CONCLUSIONS: This study showed that women who did not eat fruits, dark-green vegetables, and beans had a higher risk of genital HR-HPV infection. Intake of these food components is suggested for women to prevent HPV carcinogenesis.

Effect of HIV/HAART and Other Clinical Variables on the Oral Mycobiome Using Multivariate Analyses.

The oral microbiome is considered an important factor in health and disease. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial communities in a large cohort of HIV-positive and -negative individuals. The purpose of the present study was to similarly analyze the oral mycobiome in the same cohort. To identify fungi, the internal transcribed spacer 2 (ITS2) of the fungal rRNA genes was sequenced using oral rinse samples from 149 HIV-positive and 88 HIV-negative subjects that had previously undergone bacterial amplicon sequencing. Quantitative PCR was performed for total fungal content and total bacterial content. Interestingly, samples often showed predominance of a single fungal species with four major clusters predominated by Candida albicans, Candida dubliniensis, Malassezia restricta, or Saccharomyces cerevisiae Quantitative PCR analysis showed the Candida-dominated sample clusters had significantly higher total fungal abundance than the Malassezia or Saccharomyces species. Of the 25 clinical variables evaluated for potential influences on the oral mycobiome, significant effects were associated with caries status, geographical site of sampling, sex, HIV under highly active antiretroviral therapy (HAART), and missing teeth, in rank order of statistical significance. Investigating specific interactions between fungi and bacteria in the samples often showed Candida species positively correlated with Firmicutes or Actinobacteria and negatively correlated with Fusobacteria, Proteobacteria, and Bacteroidetes Our data suggest that the oral mycobiome, while diverse, is often dominated by a limited number of species per individual; is affected by several clinical variables, including HIV positivity and HAART; and shows genera-specific associations with bacterial groups.IMPORTANCE The oral microbiome is likely a key element of homeostasis in the oral cavity. With >600 bacterial species and >160 fungal species comprising the oral microbiome, influences on its composition can have an impact on both local and systemic health. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial community in a large cohort of HIV-positive and -negative subjects. We describe here a comprehensive analysis of the oral mycobiome in the same cohort. Similar to the bacterial community, HIV under highly active antiretroviral therapy (HAART) had a significant impact on the mycobiome composition, but with less impact compared to other clinical variables. Additionally, unlike the oral bacterial microbiome, the oral mycobiome is often dominated by a single species with 4 major clusters of fungal communities. Together, these results suggest the oral mycobiome has distinct properties compared with the oral bacterial community, although both are equally impacted by HIV.

Antioxidants Associated With Oncogenic Human Papillomavirus Infection in Women.

BACKGROUND: Human papillomavirus (HPV) infection is a major cause of cervical cancer. Studies showed the onset of HPV carcinogenesis may be induced by oxidative stress affecting the host immune system. The association between antioxidants and oncogenic HPV remains unclear. In this study, we aim to identify antioxidants associated with vaginal HPV infection in women. METHODS: The associations between the 15 antioxidants and vaginal HPV infection status (no, low-risk [LR], and high-risk [HR] HPV) were evaluated using 11 070 women who participated in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). RESULTS: We identified serum albumin and 4 dietary antioxidants (vitamin A, B2, E, and folate) inversely associated with HR-HPV infection. Women with a low level of albumin (≤39 g/L) have a significantly higher risk of HR-HPV (odds ratio [OR] = 1.4, P = .009 vs >44 g/L). A Nutritional Antioxidant Score (NAS) was developed based on these 4 dietary antioxidants. The women with the lowest quartile NAS had a higher chance of HR-HPV (OR = 1.3, P = .030) and LR-HPV (OR = 1.4, P = .002) compared with the women with the highest quartile NAS. CONCLUSIONS: We identified 5 antioxidants negatively associated with vaginal HR-HPV infection in women. Our findings provide valuable insights into understanding antioxidants' impact on HPV carcinogenesis.

Risk of abnormal cervical cytology in HIV-infected women testing positive for both human papillomavirus and Epstein-Barr virus in genital tract specimens.

PURPOSE: Although infection with high-risk human papillomavirus (HPV) is a prerequisite for cervical cancer development, HPV infection is not sufficient to promote cancer in the majority of infected women. We tested the hypothesis that human herpesviruses might cooperate with HPV to promote the development of cervical dysplasia, an early indicator of cervical cancer development. METHODS: This study used archived specimens from a cohort of human immunodeficiency virus (HIV)-seropositive women seeking gynecological care at the Medical Center of New Orleans, Louisiana. Viral DNA was detected by PCR amplification and risk of abnormal cervical cytology was determined in relation to virus test results. RESULTS: Consensus human herpesvirus PCR with herpes speciation by restriction endonuclease digestion revealed Epstein-Barr virus (EBV) to be the most prevalent herpesvirus in cervicovaginal lavage specimens. Further analysis using an EBV-specific PCR assay and cervical swab specimens demonstrated an approximately fourfold increased risk of abnormal cervical cytology in women testing positive for cervical EBV and high-risk HPV compared to women testing positive for high-risk HPV alone. This relationship was independent of markers of advancing HIV disease. CONCLUSION: Cervical shedding of EBV appears to predict a greater risk of cervical dysplasia in HIV-infected women with a high-risk HPV infection.

Significant effect of HIV/HAART on oral microbiota using multivariate analysis.

Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than the effect of gingivitis, periodontal disease, smoking, caries, and other clinical variables. In conclusion, a multivariate comparison of a large sample of persons with HIV under HAART to an HIV-negative control group showed a complex set of clinical features that influenced oral bacterial community composition, including the presence of HIV under HAART.

Cervical Human Papillomavirus Testing With Two Home Self-Collection Methods Compared With a Standard Clinically Collected Sampling Method.

BACKGROUND: The purpose of this study was to compare the outcomes of 2 self-collection methods to detect cervical human papillomavirus (HPV) DNA with outcomes from a standard clinical method. The standard method samples were collected by a clinician at a routine pelvic examination. Self-samples were taken at home and mailed to the clinical laboratory. METHODS: The 2 self-collection methods were a tampon-based method and a swab-based method using a commercial device, an Eve Medical HerSwab. All HPV samples were processed by a clinical laboratory using the Food and Drugs Administration approved Roche Cobase HPV method, which specifically identifies HPV 16, HPV 18, and a set of 12 other high-risk subtypes. Patients were recruited from 2 cancer screening clinics 2015 to 2017. All patients signed an informed consent. Screening outcomes, such as prevalence, percent agreement with standard, sensitivity, and specificity, were calculated for each self-collection method. Measures of similarity between self and standard collection outcomes, Cohen's κ, percent concordance, McNemar equivalence, and others were tested statistically. RESULTS: One hundred seventy-four patients were randomized. The prevalence of 1 or more positive HPV high-risk subtypes from the standard clinical specimens was 13.5%. All clinical specimens were sufficient for valid HPV detection. For the tampon method, 15 (27%) of the specimens were insufficient quality. Only 1 (2%) swab specimen was insufficient. Only the swab self-collection method was found to be statistically noninferior to the clinical method. The tampon method had an unacceptably high rate of insufficient quality specimens and also failed the equivalency tests. CONCLUSIONS: The swab home collection samples were equivalent to the clinical samples, but the tampon method had an unacceptably high rate of specimens insufficient for HPV detection.

Epstein-Barr Virus, High-Risk Human Papillomavirus and Abnormal Cervical Cytology in a Prospective Cohort of African Female Sex Workers.

BACKGROUND: High-oncogenic-risk human papillomavirus (hrHPV) is necessary, although insufficient, to promote cervical cancer. Like HPV, Epstein-Barr virus (EBV) is a common pathogen with the capacity to promote epithelial neoplasms. We examined the association between cervical EBV, hrHPV, and cytology in female sex workers in Nairobi, Kenya. METHODS: Women (n = 332) with known cervical cytology and hrHPV mRNA results were evaluated for cervical EBV DNA by conventional polymerase chain reaction. Prevalence ratios (PRs) were calculated to assess the relationships between EBV, hrHPV, and cervical cytology. Prospective analyses used risk ratios and time-to-event analyses to determine the association of EBV with hrHPV clearance and with abnormal cytology outcomes. RESULTS: Baseline prevalence of hrHPV and EBV was 29% and 19%, respectively. Higher EBV prevalence was found among women with older age, HIV, hrHPV, abnormal cytology, Mycoplasma genitalium infection, smoking habits, younger age at sexual debut, and less frequent condom use. At baseline, women with EBV had a higher prevalence of hrHPV infection than did EBV-negative women (52% vs. 24%; HIV-adjusted PR [95% confidence interval], 1.8 [1.3-2.6]). Epstein-Barr virus-positive women had a higher prevalence than did EBV-negative women of high-grade precancer (15% vs. 2%) and abnormal cytology (37% vs. 15%), although HIV- and hrHPV-adjusted associations were not significant (high-grade precancer: PR, 2.0 [0.7-5.9]; abnormal cytology: PR, 1.4 [0.9-2.2]). In prospective analyses, a marginal association was observed between baseline EBV detection and delayed hrHPV clearance. CONCLUSIONS: Our data support a possible role for EBV as a high-risk marker or cofactor for HPV-mediated cervical cancer development.

Human Papillomavirus Prevalence Is Associated With Socioeconomic Gradients Within a Medically Underserved Appalachian Region.

OBJECTIVES: To assess type-specific prevalence of human papillomavirus (HPV) infection in a medically underserved Appalachian area and to determine whether gradients in poverty are associated with prevalence. METHODS: Among 398 women, a validated assay tested self-collected cervicovaginal samples for 37 HPV types. Three economic strata were created based on household income: below the federal poverty level for 1 person, between the FPLs for families of 1 to 4 persons, and above the FPL for a family of 4. RESULTS: Prevalence was 55.6%, with 33% having at least 1 high-risk infection. Prevalence was 27.8% for 9-valent HPV vaccine-preventable types and 39.2% for multiple types. Compared with FPL for a family of 4, women with federal poverty level for 1 person had 3 times greater prevalence, 2.3 times greater prevalence of high-risk types, and 2.5 times greater prevalence of multiple types. CONCLUSION: Human papillomavirus prevalence was high, with one-third of the sample having at least 1 high-risk type and those in the lowest-income category being disproportionately infected.

Self-collected vaginal swabs for HPV screening: An exploratory study of rural Black Mississippi women.

OBJECTIVES: To determine the post-procedure acceptability of self-collecting a vaginal swab for HPV testing among a highly impoverished and geographically isolated population of medically underserved Black women residing in the Mississippi Delta. Further, to test correlates of reporting that self-collection is preferred over Pap testing. Finally, to determine the prevalence of any of 13 high-risk HPV types among this population and the correlates of testing positive. METHODS: Eighty-eight women were recruited from two churches located in different towns of the Mississippi Delta. After completing a survey, women were provided instructions for self-collecting a cervico-vaginal swab and completing a post-collection survey. Specimens were tested for 13 oncogenic HPV types. Due to the exploratory nature of the study, significance was defined by a 0.15 alpha-level. RESULTS: Comfort levels with self-collection were high: 78.4% indicated a preference for self-collecting a specimen compared to Pap testing. Overall, 24 women (28.7%) tested positive for one or more of the 13 HPV types. Significant associations with testing positive were found for women having sex with females (P = 0.09), those never having an abnormal Pap (P = 0.06), younger women (P = 0.10), those with greater fatalism scores (P = 0.006), and those having less trust in doctors (P = 0.001). CONCLUSIONS: Black rural women from the deep-south are generally comfortable self-collecting cervico-vaginal swabs for HPV testing. Given that nearly 30% tested positive for oncogenic HPV, and that fatalism as well a lack of trust in doctors predicted prevalence, a reasonable screening alternative to Pap testing may be community-based testing for HPV using self-collected vaginal swabs.

Clinical Case Of the Month: A 35 Year Old Woman with Abdominal Pain.

A 35 year old woman with past medical history of hypertension presented to the emergency department with chief complaint of severe abdominal pain for one week. The abdominal pain was located in the epigastrium and described as "cramping" and "intermittent". The pain intensity was quantified initially as 6 out of 10 on the pain scale. As the week progressed the pain became constant and radiated to the back. The intensity of the abdominal pain increased to 10 out of 10. The patient reported some relief from her pain while lying in the prone position. Initially the pain was associated with loose stools for several days. The loose stools resolved spontaneously and then the patient began to experience nausea and vomiting. Her medications included lisinopril-hydrochlorothiazide which she had been taking for the past five months. She had no history of alcohol, tobacco or illicit drug use.

Community-Based Screening for Cervical Cancer: A Feasibility Study of Rural Appalachian Women.

OBJECTIVES: To describe women's comfort levels and perceptions about their experience self-collecting cervicovaginal swabs for human papillomavirus (HPV) testing, to determine whether nurse-guided patient navigation increases the odds of women receiving a traditional Papanicolaou (Pap) test after HPV screening, and to test the hypothesis that women testing positive for oncogenic HPV would be more likely to have a subsequent Pap test than those testing negative. METHODS: A total of 400 women were recruited from 8 rural Appalachian counties, in 2013 and 2014. After completing a survey, women were provided instructions for self-collecting a cervicovaginal swab. Specimens were tested for 13 oncogenic HPV types. Simultaneously, women were notified of their test results and offered initial navigation for Pap testing. Chart-verified Pap testing within the next 6 months served as the end point. RESULTS: Comfort levels with self-collection were high: 89.2% indicated that they would be more likely to self-collect a specimen for testing, on a regular basis, compared with Pap testing. Thirty women (7.5%) had a follow-up Pap test. Women receiving added nurse-guided navigation efforts were significantly less likely to have a subsequent test (P = 0.01). Women testing positive for oncogenic HPV were no more likely than those testing negative to have a subsequent Pap test (P = 0.27). Data were analyzed in 2014. CONCLUSIONS: Rural Appalachian women are comfortable self-collecting cervicovaginal swabs for HPV testing. Furthermore, efforts to recontact women who have received an oncogenic HPV test result and an initial navigation contact may not be useful. Finally, testing positive for oncogenic HPV may not be a motivational factor for subsequent Pap testing.

Epidemiologic factors associated with seropositivity to human papillomavirus type 16 and 18 virus-like particles and risk of subsequent infection in men.

Our understanding of humoral response to human papillomavirus (HPV) infection has been mainly derived from studies in women. The role of serum antibodies in the natural history of HPV in men has yet to be investigated. Data from 285 male participants of a natural history study were used to determine the epidemiologic factors associated with HPV 16/18 seropositivity and explore the role of HPV 16 and 18 serum antibodies in subsequent HPV infections. Serum antibodies were detected by use of HPV 16- and 18 virus-like particles enzyme-linked immunoassay. Logistic regression and Generalized Estimating Equation was used for the evaluation of risk factors. The risk of subsequent HPV infection by baseline antibody status was assessed by incidence rate ratio and its confidence intervals. Men ages 36 to 44 years compared with men ages 18 to 25 years were four times more likely to be seropositive to HPV 16/18. In addition, being divorced, separated, or widowed; being a former smoker; and having sex with men was positively and independently associated with HPV 16/18 seropositivity. Our findings on the potential role of HPV 16 or 18 serum antibodies in subsequent infection were inconclusive. Large prospective studies are warranted to adequately address questions on the role of natural immunity in the natural history of HPV infections in men.

HPV 6/11, 16, 18 seroprevalence in men in two US cities.

BACKGROUND: A vaccine to prevent human papillomavirus (HPV) 6, HPV 11, HPV 16, or HPV 18 and associated diseases is licensed for females, and it may be licensed for men in the future. There are limited data on HPV 6/11, 16, and/or 18 seroprevalence in men. METHODS: A total of 490 men aged 18 to 40 years were enrolled in a study of HPV in men in Tucson, AZ, and Tampa, FL. Enrolled men completed a self-administered questionnaire, and HPV serology was performed using HPV 6/11, 16, and 18 VLP assays. RESULTS: Overall, seroprevalence to HPV 16 was 12.1%, HPV 6/11 was 9.7%, and to HPV 18 was 5.4%. Seroprevalence to HPV 6/11, 16, and/or 18 was 21% and was highest among 35 to 40 year olds (48%); prevalence in this age group was significantly higher compared to the 18 to 24 year olds (adjusted odds ratio (aOR) 6.8, 95% confidence interval (CI) 3.7, 12.8). Independent predictors of seropositivity to HPV 6/11, 16, and/or 18 were older age, greater number of female sex partners in the past 3 months, and current smoking. CONCLUSIONS: HPV vaccine-type seroprevalence was highest in 35 to 40 year old men. These data on the epidemiology of HPV seroprevalence in men are useful for discussions regarding recommendations for HPV vaccine if licensed for use in men.

Development and validation of a HPV-32 specific PCR assay.

BACKGROUND: Human Papillomavirus-32 (HPV-32) has traditionally been associated with focal-epithelial-hyperplasia (FEH). It is also present in 58% of oral warts of HIV-positive individuals whose prevalence is increasing. Current methods for the detection of HPV-32 are labor-intensive and insensitive so the goal of this work was to develop a highly sensitive and easy to use specific polymerase chain reaction (PCR) assay. MATERIALS AND METHODS: An HPV-32 L1 specific PCR assay was developed and optimized. The sensitivity and specificity was compared to previous assays utilized for detection (PGMY and MY09/11 PCR with dot blot hybridization) using cloned HPV-32 L1, the closely related HPV-42 L1 as well as clinical samples (oral swabs and fluids from 89 HIV-positive subjects). RESULTS: The HPV-32 specific PCR assay showed improved sensitivity to 5 copies of HPV-32 as compared to the PGMY PCR, MY09/11 PCR and dot blot which had a limit of detection of approximately 3,000 copies. Using the HPV-32 dot blot hybridization assay as the gold standard, the HPV-32 specific PCR assay has a sensitivity of 95.8% and 88.9% by sample and subject, respectively, and specificity was 87.8% and 58.8% by sample and subject, respectively. The low sensitivity is due to the HPV-32 specific PCR assays ability to detect more HPV-32 positive samples and may be the new gold standard. CONCLUSION: Due to the ease, sensitivity, and specificity the HPV-32 specific PCR assay is superior to previous assays and is ideal for detection of HPV-32 in large cohorts. This assay provides an excellent tool to study the natural history of HPV-32 infection and the development of oral warts.

Oral HPV complications in HIV-infected patients.

Human papillomavirus (HPV) infection and disease, including that of the oral cavity, has not dramatically declined since the introduction of potent combination therapy to control HIV. Two manifestations of HPV in the oral cavity that may be on the rise are HPV-32-associated oral warts and HPV-16-associated oral cancers. A current research focus is the natural history of HPV infections in the oral cavity. A better understanding of the natural history of oral HPV infections could lead to improved diagnosis and treatment for oral HPV complications in HIV-positive patients.

Human papillomavirus infection and disease in the HIV+ individual.

HPV infection of both the genital tract and oral cavity of HIV+ men and women is increased. HPV-related pathology is also increased in the HIV+ individuals, usually with further increases seen for those HIV+ individuals with lower CD4 cell counts. Fortunately, the rates of cervical cancer and anal cancer are relatively low and not related to CD4 cell count. Treatment of the HIV+ individual with HPV-related disease is challenging and requires close long-term follow-up to prevent recurrent disease. The mechanism of how HPV and HIV interact is still not known but is more likely to be linked to immune suppression rather than a direct interaction between viruses. The newly developed HPV vaccines will likely have a significant impact on HPV-related disease in immunocompetent individuals. It remains to be seen what impact these vaccine will have on the immune depressed.

The impact of highly active antiretroviral therapy and immunodeficiency on human papillomavirus infection of the oral cavity of human immunodeficiency virus-seropositive adults.

BACKGROUND: Prevalence of human papillomavirus (HPV)-associated oral condylomas has reportedly increased in HIV-infected individuals since the introduction of highly active antiretroviral therapy (HAART). The relationships between HIV therapy regimen, overall health, and subclinical oral HPV have not been examined. GOAL: To determine oral HPV genotype prevalence and the impact of HAART and health in the HIV+ population. STUDY: An L1 consensus-primer polymerase chain reaction and linear array assay were used to examine the prevalence of 27 HPV genotypes in saliva of 98 HIV+ individuals. Risk assessment variables were compared to oral HPV status. RESULTS: Oral HPV was detected in 37% of HIV+ African American individuals. Caucasians were at greater risk of oral HPV infection than African Americans. Markers of advanced HIV disease did not predict HPV status. Therapy status was associated with HPV detection. CONCLUSIONS: Treatment of HIV, rather than HIV immunosuppression, appears to play a role in oral HPV infections in HIV+ individuals.

Prevalence and clustering patterns of human papillomavirus genotypes in multiple infections.

Prevalence of multiple human papillomavirus (HPV) infections, involvement of specific HPV phylogenetic clades in multiple infections, and clustering patterns of multiple infections at the clade level were assessed in 854 HIV (-) and 275 HIV (+) women cross-sectionally. Reverse line blot assay was used to detect 27 HPV genotypes. Involvement of specific clades in coinfections and clustering patterns were assessed using HPV clade/genotype as the unit of analyses. Expected frequencies assuming independence for all possible clade combinations in two-genotype infections were derived using a multinomial expansion and comparisons of observed and expected frequencies were done using a composite goodness-of-fit test. In all, 100 two-genotype infections were detected; 61 in HIV (-) and 39 in HIV (+) women. Clade A9 (HPV types 16, 31, 33, 35, 52, and 58) was significantly less likely to be involved in multiple infections compared with all other clades (55.2% versus 64.6%; adjusted odds ratios, 0.68; 95% confidence interval, 0.48-0.95). Observed patterns for all possible clade combinations (among HPV clades A3, A5, A6, A7, A9, and A10) in two-genotype infections did not significantly differ from those expected in the entire sample, across HIV, Pap smear, and age strata (all goodness-of-fit exact P > 0.20). These results indicate that clade A9 is less likely to be involved in multiple infections and that HPV genotypes predominantly establish multiple infections at random, with little positive/negative clustering for either phylogenetically related or unrelated types. The current method of analysis affords the opportunity to test clustering of a large number of HPV genotype/clade combinations at nominal alpha levels.

The ATM/p53 pathway is commonly targeted for inactivation in squamous cell carcinoma of the head and neck (SCCHN) by multiple molecular mechanisms.

The ATM/p53 pathway plays a critical role in maintenance of genome integrity and can be targeted for inactivation by a number of characterized mechanisms including somatic genetic/epigenetic alterations and expression of oncogenic viral proteins. Here, we examine a panel of 24 SCCHN tumors using various molecular approaches for the presence of human papillomavirus (HPV), mutations in the p53 gene and methylation of the ATM promoter. We observed that 30% of our SCCHN samples displayed the presence of HPV and all but one was HPV type 16. All HPV E6 gene-positive tumors exhibited E6 transcript expression. We observed 21% of the tumors harbored p53 mutations and 42% of tumors displayed ATM promoter methylation. The majority of tumors (71%) were positive for at least one of these events. These findings indicate that molecular events resulting in inactivation of the ATM/p53 pathway are common in SCCHN and can arise by a number of distinct mechanisms.