Effects of long-term use of antiretroviral therapy on the prevalence of oral Epstein-Barr virus

J Oral Pathol Med (2012) 41 : 249–254 Background: The objectives of this study were to determine (i) the prevalence of oral Epstein–Barr virus (EBV) in HIV‐infected subjects compared to non‐HIV controls and (ii) the effects of long‐term use of antiretroviral therapy (ART) on the prevalence of oral EBV. Methods: A cross‐sectional study was performed in HIV‐infected subjects with and without ART, and non‐HIV individuals. DNA in saliva samples was extracted and used as a template to detect EBV BamH1W and EBNA1 by quantitative polymerase chain reaction. Student t‐test and ANOVA test were performed to determine the prevalence rates among groups. Results: Forty‐nine HIV‐infected subjects: 37 on ART (age range 23–54 year, mean 37 year), 12 not on ART (age range 20–40 year, mean 31 year), and 20 non‐HIV controls (age range 19–53 year, mean 31 year) were enrolled. The numbers of EBV BamH1W in saliva were found to be significantly higher in HIV‐infected subjects than non‐HIV controls (80% vs. 20%, mean = 12 118 vs. 134 copies/10⁵ cells, P < 0.001). HIV‐infected subjects who were on ART had significantly lower numbers of EBV BamH1W than those who were not (mean = 4102 vs. 138 613 copies/10⁵ cells, P = 0.011). The numbers were significantly lower in those who received long‐term ART compared with short‐term (mean = 1401 vs. 11 124 copies/10⁵ cells, P = 0.034). No significant difference was observed between the groups when using EBNA1 primers. Conclusions: Prevalence of oral EBV was significantly higher in HIV‐infected subjects than non‐HIV‐controls. The numbers of the virus were significantly decreased by ART. Long‐term use of ART did not increase oral EBV.     

Changes in oral cytokeratin expression in HIV-infected subjects with long-term use of HAART

Oral Diseases (2012) 18 , 793–801 Objectives: The objectives of this study were to determine (i) the expression of oral cytokeratins (CKs) among human immunodeficiency virus (HIV)‐infected subjects compared with non‐HIV controls, (ii) the oral CK expression in the subjects with highly active antiretroviral therapy (HAART) compared with those without HAART, and (iii) factors associated with the expression of oral CKs. Materials and methods: Oral tissues from buccal mucosa were obtained by punched biopsy in HIV‐infected subjects with and without HAART, and non‐HIV individuals. The samples were processed for immunohistochemical studies of CK1, CK13, CK14, CK16, and involucrin. The staining intensity was scored and recorded. Logistic regression analysis and multi‐way ANOVA test were performed. Results: The expression of CK13, CK14, and CK16 was found to be significantly different between HIV‐infected subjects and non‐HIV individuals (P < 0.05). The expression of those CKs was also significantly different between those who were and were not on HAART (P < 0.05). No significant difference between the groups was observed regarding CK1 and involucrin. Conclusions: Oral epithelial cell differentiation as marked by the CK expression is affected by HIV infection and use of HAART. CKs may be the useful biomarkers to identify HIV‐infected subjects who are at risk of malignant transformation of the oral mucosa because of HIV infection and HAART.     

Presence of human papilloma virus,herpes simplex virus and Epstein–Barr virus DNA in oral biopsies from Sudanese patients with regard to toombak use

J Oral Pathol Med (2010) 39 : 599–604 Using PCR/DNA sequencing, we investigated the prevalence of human papillomavirus (HPV), herpes simplex virus (HSV) and Epstein–Barr virus (EBV) DNA in brush biopsies obtained from 150 users of Sudanese snuff (toombak) and 25 non‐users of toombak in formalin‐fixed paraffin‐embedded tissue samples obtained from 31 patients with oral dysplasias (25 toombak users and 6 non‐users), and from 217 patients with oral cancers (145 toombak users and 72 non‐users). In the brush tissue samples from toombak users, HPV was detected in 60 (40%), HSV in 44 (29%) and EBV in 97 (65%) of the samples. The corresponding figures for the 25 samples from non‐users were 17 (68%) positive for HPV, 6 (24%) positive for HSV and 21 (84%) for EBV. The formalin‐fixed samples with oral dysplasias were all negative for HPV. In the 145 oral cancer samples from toombak users, HPV was detected in 39 (27%), HSV in 15 (10%) and EBV in 53 (37%) of the samples. The corresponding figures for the samples from non‐users were 15 (21%) positive for HPV, 5 (7%) for HSV and 16 (22%) for EBV. These findings illustrate that prevalence of HSV, HPV and EBV infections are common and may influence oral health and cancer development. It is not obvious that cancer risk is increased in infected toombak users. These observations warrant further studies involving toombak‐associated oral lesions, to uncover the possible mechanisms of these viral infections in the development of oral cancer, and the influence of toombak on these viruses.     

Human papilloma virus types in the oral and cervical mucosa of HIV‐positive South African women prior to antiretroviral therapy

Background: To evaluate the prevalence of human papilloma virus (HPV) infection and types in the oral and cervix mucosa of treatment‐naïve HIV‐1‐positive women with CD4 counts less than 300 cells per ml with no HPV‐associated oral lesions. Methods: Oral epithelium was harvested from the buccal mucosa and lateral borders of the tongue and cervical samples were collected from the endocervical area of 30 women, 22–64 years old. Cytobrush Plus cell collectors were used for sampling both anatomical areas. Genital pathology, obstetric and gynaecological history, co‐morbid disease, hormone therapy, sexual behavior and smoking history were assessed via physical examination and clinical interviews. Special investigations included cervical Papanicolau smears, CD4 counts and HIV‐1 viral loads. The linear array HPV test was used to determine HPV genotypes present in the specimens. Results: Oral HPV were identified in 20% (n = 6) of the patients, of which two had infection with two HPV types. Genital HPV was found in 96.7% (n = 29) of the women, of which only 14 had cytological abnormalities on Papanicolau smear. Infection with multiple HPV types were present in 93.1% (n = 27) of the patients, with an average of four HPV types per individual. Conclusions: South African HIV‐positive women with CD4 counts less than 300 cells per ml have a significant risk of cervical HPV strains and multiple strain infection of the cervix. The prevalence of HPV in normal oral mucosa was low but high‐risk types were present. Limited correlation between oral HPV types and those identified in the cervical mucosa was found.     

Effects of long‐term use of HAART on oral health status of HIV‐infected subjects

J Oral Pathol Med (2010) 39 : 397–406 Background: The aim of this study was to determine the effects of long‐term use of highly active antiretroviral therapy (HAART) on oral health status of HIV‐infected subjects. Methods: Oral examination and measurement of saliva flow rate of both unstimulated and wax‐stimulated whole saliva were performed in HIV‐infected subjects with and without HAART, and in non‐HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long‐term use of HAART on oral health status of HIV‐infected subjects. Results: One hundred and fifty‐seven HIV‐infected subjects – 99 on HAART (age range 23–57 years, mean 39 years) and 58 not on HAART (age range 20–59 years, mean 34 years) – and 50 non‐HIV controls (age range 19–59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV‐infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short‐term HAART (P < 0.01). The subjects with long‐term HAART were found to have a greater risk of having oral lesions than those with short‐term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05). Conclusion: We conclude that long‐term HAART has adverse effects on oral health status of HIV‐infected subjects.     

Association of HPV infections with second primary tumors in early-staged oral cavity cancer

Oral Diseases (2012) 18 , 809–815 Objective: The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. Materials and Methods: The study recruited 103 patients with pathological early‐stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV‐genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi‐square, Kaplan–Meier, and logrank tests. Results: Thirty‐one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease‐free survival or overall survival). However, infection with HPV‐18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. Conclusions: There are 30% of the patients with OSCC infected with HPV, with most high‐risk types. HPV‐18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.     

Prevalence of human papillomaviruses in the healthy oral mucosa of women with high‐grade squamous intra‐epithelial lesion and of their partners as compared to healthy controls

Oral human papillomavirus (HPV) carriage rates were investigated in relation to genital HPV carriage in women with HPV‐associated cervical lesions and male partner of such women, including several couples, in comparison with healthy individuals. Buccal and lingual mucosa of 60 males and 149 females with healthy oral mucosa and without known genital lesion, genital and oral mucosa of further 40 females with cervical high‐grade squamous intraepithelial lesion (HSIL) and 34 male sexual partners of women with HSIL (including 20 couples) were sampled. HPV DNA was detected using MY/GP PCR. Genotype was determined by sequencing or restriction fragment length polymorphism. Virus copy numbers were determined by real‐time PCR. Overall, oral HPV carriage rate was 5.7% (12/209) in healthy individuals; average copy number was 5.8 × 10² copies/1 μg DNA; male and female rates were comparable. Oral carriage in women with HSIL was significantly higher, 20.0% (8/40, P = 0.003); males with partners with HSIL showed a carriage rate of 17.6% (6/34), copy numbers were similar to the healthy controls. In contrast, genital carriage rate (52.9%, 18/34 vs. 82.5%, 33/40; P = 0.006) and average copy number were lower in males (5.0 × 10⁵ vs. 7.8 × 10⁵ copies/1 μg DNA; P = 0.01). Oral copy numbers in these groups and in healthy individuals were comparable. High‐risk genotypes were dominant; couples usually had the same genotype in the genital sample. In conclusion, genital HPV carriage is a risk factor of oral carriage for the individual or for the sexual partner, but alone is not sufficient to produce an oral HPV infection in most cases.     

Oral sampling and human papillomavirus genotyping in HIV-infected patients

J Oral Pathol Med (2012) 41 : 288–291 Background: Oral human papillomavirus (HPV) is associated with several health complications especially in combination with HIV infections. Screening may be useful, but methodologies and results have varied widely in previous studies. We conducted a pilot study in an HIV‐positive population to evaluate HPV detection in four different oral sample types. Methods: Upon enrollment, an oral‐rinse (OR) sample was collected in 10 ml saline. Additional samples of the buccal mucosa, tonsils, and oral lesion if present were collected with cytology brushes. DNA was extracted using LC‐MagNAPure, and the Linear Array HPV genotyping Assay (Roche) was used for HPV genotyping. Results: In samples from 100 HIV‐positive participants, HPV was detected in 39 (%) of the oral rinses, 13 (%) mucosal and 11 (12.9%) tonsil brushings. Of seven lesion brushings collected, four were HPV positive. All participants with HPV detected in mucosal, tonsil, or lesion brushings were also positive in the OR sample. Among the rinse samples, 27 different genotypes were detected with HPV84 (n = 6), HPV55 (n = 5), and HPV83 (n = 5) being the most common. Multiple infections were detected in 17 samples (range 2–9, mean 1.9 types). As potential cofactors, only receptive oral sex was significantly associated with HPV (P = 0.018, odds ratio 2.9, 95% CI 1.2–6.9). Conclusion: Sampling is a significant factor for oral prevalence studies. Oral rinse provides the best representation for HPV in the oral cavity. To evaluate associated cofactors other than receptive oral sex, larger studies with case–control design are necessary.     

Periodontal pathogens in subgingival plaque of HIV‐positive subjects with chronic periodontitis

Many putative periodontal pathogens associated with periodontal disease in human immunodeficiency virus (HIV)‐infected patients also occur in non‐HIV‐infected individuals. This study examined the prevalence of eight periodontal pathogens in HIV‐positive and HIV‐negative patients with chronic periodontitis using the 16s RNA polymerase chain reaction technique. The results showed a significant prevalence of Porphyromonas gingivalis and Treponema denticola among HIV‐negative patients compared to HIV‐positive patients. Sixty percent of the patients in both groups were colonized by five to six species. Odds ratio analysis revealed a statistically significant positive association between three of the 28 possible combinations in the HIV‐positive group. They included Prevotella nigrescens/Campylobacter rectus, P. nigrescens/P. gingivalis and P. nigrescens/T. denticola. Although the prevalence of periodontal pathogens is similar in both the groups, the combination of certain periodontal pathogens may be responsible for chronic periodontitis seen in HIV‐infected adults.     

Relevance of human papilloma virus (HPV) infection to carcinogenesis of oral tongue cancer

Human papilloma virus (HPV) infection is controversial as a causative factor in oral tongue cancer. This study aimed to clarify whether HPV directly affects the carcinogenesis and biological behaviour of oral tongue cancer by analyzing HPV prevalence, the physical status of the virus and clinicopathological parameters. Archival tissue was obtained from 36 patients diagnosed with T1 and T2 oral tongue cancer and 25 normal controls. HPV genotyping chip and real-time polymerase chain reaction were used to determine the prevalence, phenotype and physical status of HPV to clarify whether HPV directly affects oncogenesis. The results were also compared with clinicopathological parameters. HPV was detected in 36% (13/36) of oral tongue cancer patients, compared with 4% (1/25) of the control. In the HPV-positive group of oral tongue cancers, HPV-16 was the most common type and its prevalence rate was 85% (11/13). Of the HPV-16 infected oral tongue cancers, the integration rate of HPV-16 was 55% (6/11). The HPV-16 positive group showed shallower stromal invasion than the HPV-16 negative group (p = 0.045). HPV-16 may be one of the causative factors in early squamous cell oral tongue carcinoma and be associated with its depth of invasion.     

Mode of HIV transmission associated with risk of oral lesions in HIV‐infected subjects in Thailand

J Oral Pathol Med (2010) 39 195–200 Background: The aim of this study was to determine if route of human immunodeficiency virus (HIV) transmission is associated with the risk of oral lesions in HIV‐infected subjects in Thailand. Methods: A cross‐sectional study was performed in 186 HIV‐infected heterosexuals (aged 21–65 years, mean 32 years), and 82 HIV‐infected intravenous drug users (IVDUs) (aged 16–50 years, mean 30 years). The following information was recorded: route of HIV transmission, total lymphocyte cell counts, weight, smoking habit, alcohol consumption, medications, presence of denture, plaque index, and presence of oral lesions. The association between mode of HIV transmission and the risk of oral lesions among the subjects was determined by multiple logistic regression analysis. Results: Oral lesions were found in 138 HIV‐infected heterosexuals (75%) and in 37 HIV‐infected IVDUs (46%). Oral candidiasis (OC) was the most common lesion among both groups (44% vs. 28%), followed by hairy leukoplakia (HL) (33% vs. 10%). Multiple logistic regression analysis showed a significant association between mode of HIV transmission and the risk of oral lesions after controlling for the total lymphocyte cell counts and other confounding factors [OR 3.1; 95% CI 1.5–6.4; P = 0.002]. OC was significantly associated with heterosexual route of HIV transmission [OR 2.4; 95% CI 1.2–4.7; P = 0.014]. Similar association was also observed with HL [OR 3.7; 95% CI 1.5–9.1; P = 0.004]. Conclusions: Mode of HIV transmission is associated with the risk of oral lesions in HIV‐infected subjects in Thailand. Further studies should be performed to determine if the risk of oral lesions is associated with differences in HIV‐subtypes.     

PL7Oral viral infections that could be transmitted oro‐genitally

Orogenital transmission has been suggested for several viruses, e.g. herpes simplex virus‐1 and ‐2 (HS‐1 and HSV‐2), Epstein‐Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus‐8 (HHV‐8), human papillomavirus (HPV) and HIV. Most studies have focused on HIV, HSV and HPV. Unprotected orogenital contact, especially receptive oral intercourse, is associated with greater risk of HIV transmission than previously thought. Factors potentially associated with increased risk of HIV transmission through oral sex include poor oral health, the salivary anti‐HIV properties such as peroxidases and thrombospondin‐1, the local and systemic immunological responses, concomitant sexually transmitted infections, ejaculation in the mouth, local mucosal integrity, and the level of infectious HIV present at the oral mucosa. The probability of per act transmission in oral intercourse with ejaculation is 0.04%. HSV‐2 has been regarded as a sexually transmitted virus while HSV‐1 is causing primary herpetic gingivo‐stomatitis, muco‐cutaneous oro‐facial disease and ocular disease. Also HSV‐2 might be detected occasionally in oro‐facial area. Recent data on young women with a primary genital infection indicate that HSV‐1 is much more frequent than HSV‐2. Oro‐genital route of transmission is more common than expected in genital HSV‐1 infections. EBV is a tumorigenic herpes virus that is carried as a persistent infection by more than 90% of adults. Most persistently infected people produce EBV in their saliva, and transmission is through close contact. There is a significant association between sexual intercourse and EBV seropositivity, increasing with numbers of sex partners. Because EBV has been found in genital secretions from healthy seropositive men and women, direct spread of virus during sexual intercourse is possible. Today, 106 HPV types have been sequenced of which almost 40 have been detected also in oral mucosa, causing benign epithelial lesions (papillomas, condylomas, warts and focal epithelial hyperplasia, or FEH). Recent meta‐analyses of the case‐control studies have confirmed HPV as an independent risk factor for oral SCC with odds ratios (OR) 3.7 to 5.4. HPV16 is the overwhelmingly most frequent type. HPV has been regarded as a sexually transmitted disease but this view is challenged by frequent detection of HPV in children. Unlike in genital tract, natural history of oral HPV infection is poorly studied. As part of the Finnish HPV Family Study we evaluated natural history of oral HPV in within family members. The detection rate of HR HPVs varied from 15% to 27%. Our results indicate that natural history of HPV infection in oral mucosa mimics that of genital HPV infections. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection in the other spouse 10‐fold.     

US1HIV – changing patterns in HAART era,patients’ quality of life and occupational risks

Oral manifestations are early and important indicators of HIV‐infection. Several lesions with strong association to HIV infection have been described: oral candidiasis (OC), oral hairy leukoplakia (OHL), Kaposi's sarcoma (KS), Non‐Hodgkin‐Lymphoma (NHL), necrotising ulcerative gingivitis and periodontitis. These lesions may be present in up to 50% of patients with HIV‐infection and up to 80% of those with AIDS. Changing patterns in HAART era: With the advent of highly active antiretroviral therapy (HAART) the prevalence of OC, OHL and HIV – associated periodontal disease has decreased in adults. The prevalence of KS has not changed. However, there has been an increase in HPV‐associated oral lesions (papillomas, condylomas and focal epithelial hyperplasia) and HIV‐related salivary gland disease. In children receiving HAART no change in the prevalence of HIV‐related oral lesions has been found. Quality of life: The presence of oral lesions has a marked impact on health related quality of life. HIV‐associated orofacial lesions may lead to facial disfigurement (KS, NHL) or may impair speech and swallowing. Consequently, weight loss and pain may be result. Studies have shown that patients with OC, angular cheilitis and OHL have a high score of decayed teeth (DMFT). Xerostomia and taste disturbances may also be factors with impact on quality of life. Occupational risks: Occupational exposure to HIV has resulted in 57 documented cases of HIV sero‐conversion among healthcare workers in the US (December 2001). Exposure to HBV and HCV carries a much higher risk of occupational infection than that for HIV‐exposure.     

Prevalence of oral mucosal lesions in adults undergoing highly active antiretroviral therapy in Hong Kong

Aim:  Highly active antiretroviral therapy (HAART) has altered the prevalence and incidence of oral mucosal lesions of HIV infection. Recent reports show a variation in the prevalence of oral mucosal lesions in different population groups. Understanding the prevalence of these lesions is of paramount importance in the efficient delivery of dental care to such cohorts. The aim of the present study was to investigate the prevalence of oral mucosal lesions and salivary parameters during HAART in an ethnic Chinese cohort in Hong Kong. Methods: A cross‐sectional estimation of the prevalence of oral mucosal lesions was carried out in 101 HIV‐infected ethnic Chinese in Hong Kong using the European Community–Clearinghouse classification. Results: The prevalence of oral mucosal lesions was more common in patients who were classified at baseline as Centers for Disease Control (CDC) C3 category than CDC A2, A3, B2, and B3 (P < 0.05). An overall prevalence of 1.98% was observed for oral Kaposi’s sarcoma. Additionally, the HIV group on HAART (0.37 ± 0.23 mL/min) had significantly lower salivary flow rates (P < 0.01) compared with the healthy group (0.49 ± 0.15 mL/min). Conclusions: Although HAART appears to markedly reduce the prevalence of oral mucosal lesions during the course of HIV disease, regular systematic oral screening is still warranted for such populations for the early diagnosis and management of pathologies, such as Kaposi’s sarcoma.     

Prevalence of oral disease among adults with primary HIV infection

Objective: To explore the type and prevalence of oral mucosal lesions among adults with primary HIV infection (PHI) compared with HIV‐negative adults at high risk for HIV disease, and in relation to HIV viral load. Methods: We conducted standardized oral examinations to identify specific oral mucosal lesions among adults with PHI, both pre‐seroconversion and post‐ seroconversion‐recently infected, compared with HIV‐negative adults. We compared the group with oral lesions to those without oral lesions with respect to HIV‐RNA load and CD4 + T‐cell count. Results: Among 115 adults (predominantly men), pseudomembranous candidiasis was the most common oral lesion among those with PHI, and was found in 4% of the 23 participants in pre‐seroconversion and in 9% of 69 participants with post‐seroconversion recent infection, compared with none found among 23 HIV negatives. Among those with PHI, the median viral load was higher and the median CD4 + T‐cell count lower among the 15 participants with an oral lesion of any type than among the 77 participants without oral lesions (P = 0.02 and 0.04, respectively). Conclusion: This finding suggests that individuals with PHI who have oral lesions may be more likely to transmit HIV because of their higher viral load.     

Oral bacteria induce a differential activation of human immunodeficiency virus‐1 promoter in T cells,macrophages and dendritic cells

Introduction: The human immunodeficiency virus (HIV) can integrate into T cells, macrophages and dendritic cells resulting in a latent infection. Reports have also demonstrated that various microbial and host cell factors can trigger HIV reactivation leading to HIV recrudescence, potentially undermining highly active antiretroviral therapies. Methods: This study evaluated the capacity of oral bacteria associated with chronic periodontal infections to stimulate HIV promoter activation in various cell models of HIV latency. Results: T cells (1G5) challenged with oral bacteria demonstrated a dose–response of HIV promoter activation with a subset of the bacteria, as well as kinetics that were generally similar irrespective of the stimuli. Direct bacterial challenge of the T cells resulted in increased activation of approximately 1.5‐ to 7‐fold over controls. Challenge of macrophages (BF24) indicated different kinetics for individual bacteria and resulted in consistent increases in promoter activation of five fold to six fold over basal levels for all bacteria except Streptococcus mutans. Dendritic cells showed increases in HIV reactivation of 7‐ to 34‐fold specific for individual species of bacteria. Conclusion: These results suggested that oral bacteria have the capability to reactivate HIV from latently infected cells, showing a relationship of mature dendritic cells > immature dendritic cells > macrophages ≥ T cells. Expression of various pattern recognition receptors on these various cell types may provide insight into the primary receptors/signaling pathways used for reactivation by the bacteria.     

Oral hairy leukoplakia is not a specific sign of HIV-infection but related to immunosuppression in general

Oral hairy leukoplakia (HL) has been regarded as an early sign of HIV infection, and its clinical importance related to the poor outcome of the patients has been emphasized. Initially, HL was observed exclusively among male homosexuals, but subsequently demonstrated in all risk groups of HIV infection. The patient described in this article suggests that oral HL is not specific for HIV infection per se, but may be associated with immunosuppression also due to other causes. We describe an HIV-seronegative, heterosexual man suffering from an acute myeloblastic leukemia, who developed clinically and histologically typical HL while on cytostatics. Biopsy showed areas with characteristic ballooning cells, and hyphae of yeasts were demonstrated with PAS-stain. Using the in situ hybridization technique, Epstein-Barr virus (EBV) DNA with high copy numbers was disclosed in the superficial and intermediate cells, whereas human papillomavirus (HPV) DNA (types 6, 11, 16, 18) was not present.     

Human papillomavirus and oral and oropharyngeal carcinoma: the essentials

There is a global increase in the prevalence of human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinoma (OPSCC) in Australia and New Zealand. Risk factors for HPV‐positive OPSCC are male gender, white race, age older than 40 but younger than 59 years old, having multiple lifetime sex partners, having oro‐genital and oro‐anal sex. High‐risk HPV subtypes play a major role in the pathogenesis of OPSCC, however, they play a much lesser role in oral squamous cell carcinoma (OSCC). Among the laboratory tests used to detect oncogenic HPV infection, polymerase chain reaction is a sensitive method but does not reflect the role of HPV in oncogenesis. While widely used, p16 immunohistochemistry is both a sensitive and a specific surrogate marker for oncogenic HPV infection in OPSCC, but not in OSCC. However, it is a useful prognostic marker in OPSCC. The current gold standard to accurately detect oncogenic HPV infection is E6/E7 mRNAin situ hybridization. Because both HPV‐positive and p16‐positive OPSCC have better short‐term prognoses there is current debate and trials on treatment de‐escalation in HPV‐positive OPSCC. Dental practitioners can play an important role in early diagnosis of HPV‐positive OPSCC.