In developing countries, the variations in the clinical spectrum of human immunodeficiency virus (HIV)-related oral lesions over time, and the possible effects of antiretroviral therapy, have not been described. In this study we evaluate the clinical spectrum of oral lesions in a series of HIV-infected patients when first examined at the acquired immunodeficiency syndrome (AIDS) clinic of a tertiary care institution in Mexico City, Mexico, and the changes observed over 12 years. All HIV-infected adult patients had an oral examination performed by specialists in oral pathology and medicine who used established clinical diagnostic criteria for oral lesions. Four periods were defined according to the evolving pattern of antiretroviral use: the first 2 were before the introduction of highly active antiretroviral therapy (HAART) and the last 2 were during more established use of HAART. For the statistical analysis the chi-square test for contingency tables and the chi-square test for trend were utilized. For dimensional variables, except age, the Kruskal-Wallis or Mann-Whitney rank sum tests were used when applicable and trend was tested with the Spearman correlation coefficient. Age was tested through analysis of variance (ANOVA) and linear regression analysis. Alpha value was set at p = 0.05 for each test. In the 12-year study, 1,000 HIV-infected patients were included (87.9% male). At the baseline examination, oral lesions strongly associated with HIV were present in 47.1% of HIV-infected patients. Oral candidosis (31.6%), hairy leukoplakia (22.6%), erythematous candidosis (21.0%), and pseudomembranous candidosis (15.8%) were the most frequent lesions. Oral Kaposi sarcoma (2.3%), HIV-associated periodontal disease (1.7%), and oral non-Hodgkin lymphoma (0.1%) were less frequent. HIV-related oral lesions decreased systematically-by half during the course of the 4 study periods (p < 0.001). Except for Kaposi sarcoma, all oral lesions strongly associated with HIV showed a trend to decrease significantly during the study period. No apparent variation in the occurrence of salivary gland disease or human papillomavirus-associated oral lesions was found. A significant trend to a lower prevalence was observed in the group of patients who were already taking antiretroviral therapy, non-HAART and HAART (p < 0.001 and p = 0.004, respectively). Only a discrete reduction, barely significant, was noted among untreated patients (p = 0.060). By Period IV (1999-2001), those who received HAART showed the lowest prevalence of oral lesions strongly associated with HIV (p < 0.001). Patients with oral lesions strongly associated with HIV had significantly lower median CD4+ counts and higher viral loads than those without oral lesions strongly associated with HIV (p < 0.001 and p = 0.005, respectively). When CD4+ counts were correlated with prevalence of oral candidosis, a consistently negative association was found; this association prevailed even after the study group was partitioned according to period. In this selected cohort of 1,000...

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Human immunodeficiency virus-related oral lesions (HIV-OLs), such as oral candidiasis (OC) and oral hairy leukoplakia (OHL), have been recognized as indicators of immune suppression since the beginning of the global HIV epidemic. The diagnosis and management of HIV disease and spectrum of opportunistic infection has changed over the past 30 years as our understanding of the infection has evolved. We investigated the following controversial topics: (i) Are oral manifestations of HIV still relevant after the introduction of highly active antiretroviral therapy (HAART)? (ii) Can we nowadays still diagnose HIV infection through oral lesions? (iii) Is the actual classification of oral manifestations of HIV adequate or does it need to be reviewed and updated? (iv) Is there any novelty in the treatment of oral manifestations of HIV infection? Results from extensive literature review suggested the following: (i) While HAART has resulted in significant reductions in HIV-OLs, many are still seen in patients with HIV infection, with OC remaining the most common lesion. While the relationship between oral warts and the immune reconstitution inflammatory syndrome is less clear, the malignant potential of oral human papillomavirus infection is gaining increasing attention. (ii) Effective antiretroviral therapy has transformed HIV from a fatal illness to a chronic manageable condition and as a result expanded screening policies for HIV are being advocated both in developed and in developing countries. Affordable, reliable, and easy-to-use diagnostic techniques have been recently introduced likely restricting the importance of HIV-OLs in diagnosis. (iii) The 1993 EC-Clearinghouse classification of HIV-OLs is still globally used despite controversy on the relevance of periodontal diseases today. HIV-OL case definitions were updated in 2009 to facilitate the accuracy of HIV-OL diagnoses by non-dental healthcare workers in large-scale epidemiologic studies and clinical trials. (iv) Research over the last 6 years on novel modalities for the treatment of HIV-OLs has been reported for OC and OHL.

Infection with human papillomavirus-16 (HPV-16) is the cause of most anogenital carcinomas. This virus is also detected in about 20% of all head and neck squamous cell carcinomas. While there is strong evidence for a causal etiological role in the case of tonsillar carcinomas, causal association with malignant lesions of the oral cavity is not yet conclusive. Our previous investigations of HPV-16 DNA methylation in anogenital sites have identified hypermethylation of the L1 gene and part of the long control region in many malignant lesions, but rarely in asymptomatic infections and low-grade precancerous lesions. Here, we report hypermethylation of this diagnostically important segment of the viral DNA in 10 out of 12 HPV-16 positive oral carcinomas from Mexican patients. These data indicate epigenetic changes of HPV-16 in oral carcinomas similar to those in anogenital carcinomas, suggesting carcinogenic processes under the influence of HPV-16 in most if not all of these oral malignant lesions. ' 2007 Wiley-Liss, Inc.Key words: papillomavirus; carcinoma; head and neck cancer; oral cavity; DNA methylation; DNA recombination; etiology; progression; Infection with human papillomaviruses (HPVs), notably with high-risk HPV types such as HPV-16 and 18, is a necessary step in the etiology of anogenital cancers, specifically carcinoma of the cervix uteri. This notion is based on epidemiological research that identified a high relative risk of carcinogenic progression associated with high-risk HPV infection, DNA diagnosis that confirmed the presence and transcription of HPV genomes in all cervical carcinomas, and the study of HPV oncoproteins that catalyze a variety of molecular mechanisms that convert normal into malignant cells. [1][2][3][4][5][6] In case of head and neck squamous cell carcinomas (HNSCCs), an HPV dependent etiology is not as consistently confirmed as in anogenital cancers. Approximately 80% of all HNSCCs do not contain HPV genomes, and must therefore originate from HPV independent etiological processes, likely including mutational events triggered by tobacco and alcohol consumption. However, there is extensive evidence that a proportion of all HNSCCs contain DNA of high-risk HPV types. 7-14 Among head and neck sites, squamous cell carcinomas of the tonsils have the strongest statistical support for an HPV dependent etiology. 9,[15][16][17] There is less strength and consistency for a linkage between HPV infection and carcinogenesis at sites of the oral mucosa such as tongue, palate, floor of mouth and gingiva. Nevertheless, epidemiological studies have established statistical evidence for a causal association of HPVs and malignancies even for these oral sites. 9,16 In addition, analysis of some HPV containing oral carcinomas revealed recombination between HPV genomes and cellular DNA as well as HPV oncogene expression, [10][11][12][13][18][19][20] properties that are generally viewed as support of carcinogenic processes under the influence of HPVs. On the basis of these observations one must conclude ...