Human Papillomavirus Positive Cases Research Articles

Abstract 4776: Expression of Human Papillomavirus E6 and E7 genes in colorectal cancer.

Abstract Purpose: The role of human papillomavirus (HPV) has been well established in the pathogenesis on cervical cancers and anogenital. However, HPV-DNA has also been detected in tumor tissues of other malignancies such as head and neck cancer, esophageal cancer, and some skin cancers. Viral genes expression and multiplication occur exclusively in the nuclei of the infected cells and are tightly linked to the state of differentiation of the cells. Integration of viral DNA into host genome is essential for carcinogenesis since it promotes disruption of HPV E2 gene, leading to abnormal expression of E6 and E7 oncoproteins. Both E6 and E7 can form specific complexes with tumor suppressor gene p53 and pRB respectively. However, the role of HPV in the pathogenesis of colorectal cancer is still undetermined. Our objectives were (1) to evaluate the presence of HPV infection in patients with CRC; (2) to type HPV positive cases using primer specific for HPV-16, and (3) to determine the mRNA expression levels of the viral oncogenes HPV-16 E6 and HPV-16 E7. Experimental Designs: To determine the association of HPV and CRC, we conducted an age-and-gender matched case-control study using tumor and tumor-adjacent colorectal tissues from patients with CRC (cases) and without CRC (controls). Presence of L1, E2, and E6 genes was analyzed to determine whether a full-length HPV genome existed in tumor and normal tissue samples. Human HPV-16 DNA detection was performed by a nested PCR strategy using the PGMY09/PGMY11 as outer primer, and GP5+/GP6+ as inner primers. We detected the expression of E6 and E7 mRNA in the HPV-16 (+) cases. Hypothesis testing was performed using Pearson Chi-square analysis of proportions and conditional logistic regression using SPSS 17. Results: A total of 54 (ß-actin+) CRC patients (mean age 61 ±11 years, 27 males) and 36 controls (mean age was 60 ± 9 years, 18 males) were evaluated. HPV DNA was identified in 25 of 54 (46.3%) patients with CRC and in 1 of 36 (2.8%) controls (OR = 25.58; 95% CI 3.22 to 203.49, p < 0.001). HPV-16 was identified in 18 of 25 (72.0%) HPV-positive CRC cases, and in one (2.8%) control was HPV (+). All 18 HPV-16 CRC cases showed expressed E6 mRNA. Six of 18 (33.3%) HPV-16 positive cases expressed E7 mRNA. Among the 12 CRC cases where both tumor and adjacent tissue was available, 2 of 9 (16.7%) exhibited HPV-16 DNA in both tumor and tumor-adjacent tissues. Conclusion: These results support that colorectal HPV infection is common among patients with CRC. The high presence of HPV in tumors located proximal to the rectum suggests that this infection might not result from direct spread from anogenital sites. Moreover, our finding of highly frequent active expression of E6 and E7 viral oncogenes in the host strongly suggests that HPV oncoproteins may play a role in the pathogenesis of colorectal carcinogenesis. Citation Format: Wesley Villavicencio-Torres, Mercedes Y. Lacourt-Ventura, Sharon C. Fonseca-Williams, Maria Del Mar Gonzalez- Pons, Yaritza Diaz-Algori, Carlos Torres-Ramos, Raul D. Bernabe-Dones, Marcia R. Cruz-Correa. Expression of Human Papillomavirus E6 and E7 genes in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4776. doi:10.1158/1538-7445.AM2013-4776

Spindle Cell Carcinomas of the Head and Neck Rarely Harbor Transcriptionally-Active Human Papillomavirus

Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma characterized by spindled or pleomorphic cells which appear to be a true sarcoma but are actually epithelial. Some head and neck squamous cell carcinoma variants can be human papillomavirus (HPV)-related and have improved outcomes. We sought to determine if spindle cell carcinomas are associated with transcriptionally-active HPV. Cases of spindle cell carcinoma were retrieved from department files. Transcriptionally-active HPV was determined by mRNA in situ hybridization for high risk HPV E6 and E7 transcripts and by a surrogate marker, p16 immunohistochemistry, with a 50% staining cutoff. RT-PCR for high risk HPV mRNA was performed on the cases that were technical failures by in situ hybridization. Medical records and follow up information were retrieved for all patients. Of 31 cases, 5 were from the oropharynx, 12 from the oral cavity, and 14 from the larynx or hypopharynx. One purely spindled oral cavity spindle cell carcinoma was HPV positive. It was also diffusely positive for p16. Another laryngeal spindle cell carcinoma was HPV positive in both the squamous and spindle cell components, but was negative for p16. None of the five oropharyngeal spindle cell carcinomas were positive for p16 or HPV RNA. The HPV positive patients both presented at high stage (IV) and died with disease within 2 years of diagnosis. The majority of spindle cell carcinomas of the head and neck, including those arising in the oropharynx, are not related to transcriptionally active HPV. Although the number of cases is too small for any definitive conclusions, for the rare HPV positive spindle cell carcinoma cases, positive viral status does not appear to confer any prognostic benefit.

Human papilloma virus genome is rare in North American non-small cell lung carcinoma patients

The reported prevalence for presence of human papillomavirus (HPV) genome in lung cancer varies across the world, and limited data are available for North America. P16 immunostaining is used as a surrogate marker for the presence of HPV in cervical and head and neck cancers. In non-small cell lung carcinoma (NSCLC), the association between P16 protein overexpression and HPV remains unclear. We investigated the presence of HPV genome by in situ hybridization (ISH) and polymerase chain reaction (PCR) and P16 or Rb protein expression by immunohistochemistry (IHC) in 336 surgically resected primary NSCLC: 204 adenocarcinoma (AdC) and 132 squamous cell carcinoma (SqCC). HPV genome was detected in 5 (1.5%) of 336 tumors studied by both ISH and PCR; all of them were typed as HPV16 and found in SqCC (3.8%). Despite being solitary tumors and clinically considered as primary lung cancers, all 5 patients had past history of HPV associated squamous cell carcinomas of other organ sites, thus highly suggestive of being metastases. P16 immunostaining was found in 137 (40.8%) tumors, with 109 (32.4%) showing high level expression. All HPV positive (+) cases showed P16 high expression. P16 and Rb protein expressions were inversely correlated (P<0.001), suggesting that the high P16 expression is largely driven by non-HPV loss of Rb protein expression. We conclude that HPV is not or rarely associated with NSCLC in Canadian and most likely North American patients, and P16 immunostaining is not a surrogate marker for its presence.

Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease

BackgroundInformation on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development.MethodsEstimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases.ResultsRC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p < 0.0001), driven by the decrease in older ages of HPV 16/18/45. In contrast, the RC of HPV 31/33/52/58 increased with age. Due to population growth alone, projected estimates of ICC cases attributable to the 9 types are expected to rise from 493,770 new cases in 2012 to 560,887 new cases in 2025.The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC.ConclusionsThe addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced.

Type‐specific human papillomavirus distribution in invasive cervical carcinomas in Paraguay. A study of 432 cases

Cervical carcinoma is the most common malignant tumor among woman in Paraguay. Cytological screening programs have not been successful and a plan for human papillomavirus (HPV) based-screening program and/or vaccination is under evaluation. This study aimed to identify the contribution of HPV genotypes in invasive cervical cancer in Paraguay to provide essential background data to guide and assess the introduction and impact of new preventive strategies based on HPV. Four hundred thirty two histologically confirmed cases (1960-2004) were analyzed. HPV detection in paraffin blocks was performed at the Catalan Institute of Oncology using PCR with SPF-10 broad spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe analysis. The majority of cases were squamous cell carcinoma (92.8%). Mean patients age was 48 years old. HPV DNA was detected in 73.1% of the cases and single infections were predominant (97.8%). The most common HPV single types were 16, 18, 45, 33, 31, 52, 35, and 39. 73.1% of HPV positive cases had an HPV 16, 18 as single infection. HPV16 was frequent in SCC whereas HPV 18 and 45 were prevalent in glandular tumors. Significant decrease of HPV 16 with age groups (P-trend = 0.022) and increase in other HPV types (P-trend > 0.001) were observed. The potential impact of HPV 16 and 18 for a vaccination program was 73.1%. The study provide a profile of the HPV situation in the country, with robust clinical, pathological and virological data which would permit a better cervical cancer screening and vaccination programs.

Prevalence and genotype distribution of human papillomavirus infection among female sex workers in Guangxi, China: Implications for interventions

Human papillomavirus (HPV) infection is a major public health concern in women, but information on HPV among female sex workers in China is limited. The aim of the study was to estimate the prevalence and genotype distribution of HPV infection among female sex workers in two cities in Guangxi, China. A total of 811 female sex workers were recruited from venues between July and September of 2009. Data on socio-demographic and behavior characteristics were collected, and cervical swabs were collected to determine HPV infection and genotype distribution. The overall prevalence of infection with any HPV type was 38.9%. HPV type 52 was the most prevalent type with prevalence of 11%, followed by HPV types 16, 58, 53, and CP8304, with prevalences of 6.5%, 5.7%, 5.6%, and 4.8%, respectively. HPV 16 or 18 accounted for 23.2% of all HPV positive cases. Age group <20 years was significantly associated with infection of the high-risk and multiple types of HPV infection. A higher prevalence of multiple HPV infection was observed among female sex workers from the outdoor venues (14.0%; 95%CI, 10.6%-17.3%). These findings have important implications for developing HPV prevention programs including HPV vaccination in female sex workers.

Human papillomavirus genotype detection in recurrent respiratory papillomatosis (RRP) in Colombia

Knowledge on human papillomavirus (HPV) genotype distribution in recurrent respiratory papillomatosis (RRP) is essential to assess the impact of HPV vaccine. It is provided information for Colombia. In all, 189 RRP primary cases diagnosed between 1985 and 2009 were identified from 5 pathology laboratories of Cali and Medellin, Colombia. HPV DNA testing in 129 cases that fulfilled inclusion criteria (available paraffin blocks, amplifiable DNA, and confirmed histologic diagnosis of RRP) was performed by the SPF-10/LiPA25 assay (version 1). Of all cases 36.1% were juvenile (<12 years old) and a majority of adults were males (p = .09); 95% of cases were HPV positive. HPV 6, 11, and 16 contributed to 69%, 27.1%, and 7.8% of all HPV positive cases. Twelve cases (9.3%) showed multiple infections; 8 of these were HPV 6 or 11 positive. HPV prophylactic vaccine including HPV 6 and 11 may have a major impact against RRP.

Discrimination of ‘Driver’ and ‘Passenger’ HPV in Tonsillar Carcinomas by the Polymerase Chain Reaction, Chromogenic In Situ Hybridization, and p16INK4a Immunohistochemistry

Human papillomavirus (HPV) positive tonsillar squamous cell carcinoma (TSCC) is associated with a favorable clinical outcome. However, the HPV detected in a given tumor may be causal (driver HPV) or an incidental bystander (passenger HPV). There is a need to discriminate these forms of HPV in TSCCs to understand their impact on HPV as a biomarker for use in TSCC patient management. This study has compared the polymerase chain reaction (PCR), chromogenic in situ hybridization (CISH), and p16(INK4a) immunohistochemistry in the assessment of HPV status in TSCC. Archival specimens of TSCC from thirty patients were investigated. HPV was detected by PCR in 25/30 (83.3%) tumors; HPV16 (70.0%) and HPV52 (6.7%) were the most common types. HPV was corroborated by CISH in 22/25 (88.0%) specimens; integrated HPV was implicated by the presence of punctate signals in each of these cases. p16(INK4a) staining was found in 20/22 (90.9%) HPV PCR positive samples; two PCR/CISH HPV positive cases were p16(INK4a) negative and two HPV negative samples were p16(INK4a) positive. These data suggest that a minority of HPV positive TSCCs are positive for passenger HPV and that two or more assays may be required for diagnosing driver HPV status. Further studies are required to exam whether oropharyngeal tumors positive for passenger HPV have a less favorable prognosis than tumors that are driver HPV positive. The clinical significance of TSCCs that test HPV negative/p16(INK4a) positive, PCR and CISH HPV positive/p16 (INK4a) negative, or PCR HPV positive/p16 (INK4a) and CISH negative, also requires further investigation.

Prevalence of Human Papillomavirus (HPV) types in cervical cancer 2003–2008 in Stockholm, Sweden, before public HPV vaccination

Background. Human papillomavirus (HPV) infection is the major cause of cervical cancer, but the prevalence of different HPV types varies depending on geographical location and may change dramatically after introduction of HPV vaccination. Here, we aimed to gain some information regarding the recent prevalence of different HPV types, in cancer of the uterine cervix in the Stockholm region, before the introduction of public HPV vaccination in Sweden. Material and methods. From 215 diagnosed cervical cancer patients 2003–2008 at the Karolinska University Hospital, 160 pretreatment cervical cancer samples, including both squamous cell carcinomas (SCC) and adenocarcinomas (ADC) could be obtained. DNA was extracted from 154/160 of the SCC and ADC samples and assayed by Luminex Multiplex for 24 different HPV types, including 15 high-risk (HR), three putative HR and six low-risk types (LR). Results. We successfully analysed 154/215 (71.6%) of the locally diagnosed cases and found a high prevalence of HPV with 92.9% in all uterine cervix cancer cases, and 93.3% and 91.4 % in SCC and ADC, respectively. All HPV positive cases harboured HR types, either alone or as multiple infections. In SCC HPV16 dominated and together with HPV18 accounted for 69.7% of the cases, followed in prevalence by HPV33, 31 and 45. In ADC, HPV18 was more common than HPV16, and they were observed in all except one of the HPV positive samples. Conclusion. The prevalence of HPV16 and 18, followed by HPV33, 31 and 45 is high in SCC and ADC in the Stockholm region. Public HPV vaccination could potentially inhibit a large proportion of such tumours underlining the urgency to initiate HPV vaccination.

Defining the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion encompassing human papillomavirus infection in relation to human papillomavirus deoxyribonucleic acid testing

Background:Human papillomavirus (HPV) infection as of now has been beyond doubt to be the causative agent for cervical carcinoma. Its morphological identification in Pap smear is important.Aim:To define the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion (SIL) encompassing HPV infection in relation to positivity for ‘high risk’ HPV16 as well as for ‘low risk’ HPV6/11.Materials and Methods:A total of 3000 Papanicolaou smears were screened, of which 150 were reported as low grade-SIL encompassing HPV infection (LSIL-HPV). Subsequently cervical scrapes from these 150 subjects, along with equal number of normal women as controls, were collected and processed for HPV deoxy-ribonucleic acid testing by polymerase chain reaction (PCR).Results:On the basis of cytomorphological characteristics in Pap smears, HPV infection were categorized into the following two groups: Classical (koilocytic) changes (CC) encountered in 30 women and non-classical changes (NCC) encountered in 120 women. It was observed that 21 (70%) CC and 46 (38.3%) NCC of HPV infection were positive for HR-HPV16; however only 12 cases (10%) of NCC and two cases (6.6%) of CC were positive for LR-HPV 6/11. Majority (41.7%) of HPV positive cases were reported in the age group of 25 to 30 years and HPV positivity decreased with the increasing age.Conclusion:Classical cellular changes are not the only diagnostic features for HPV infection in Pap smear, non-classical diagnostic features also support the diagnosis of HPV infection and may be positive for HR-HPV16.

Human Papilloma Virus prevalence and type-specific relative contribution in invasive cervical cancer specimens from Italy

BackgroundCervical cancer represents an important global public health problem. It is the 2nd most common cancer among women worldwide. Human Papillomavirus (HPV) infection is now well-established as a necessary cause of invasive cervical cancer (ICC) development. Only a few studies on HPV prevalence and type-specific distribution in ICC have been conducted in Italy.AimTo describe the prevalence of HPV and the HPV type-specific distribution in ICC cases identified in Rome, Italy.Methods140 paraffin embedded tissue blocks of primary ICC diagnosed between 2001 and 2006 were identified at the Regina Elena Cancer Institute in Rome (Italy). HPV was detected through amplification of HPV DNA using SPF-10 HPV broad-spectrum primers followed by DEIA and then genotyping by LiPA25 (version 1).Results134 cases were considered suitable for HPV DNA detection after histological evaluation; and overall, 90.3% (121/134) HPV prevalence was detected. 111 cases had a single HPV type, 4 cases had an uncharacterized type (HPVX) and 6 cases had multiple HPV infections. The five most common single HPV types among positive cases were: HPV16 (71/121; 58.7%), HPV18 (12/121; 9.9%), HPV31, HPV45 and HPV58 (5/121; 4.1% each). 2 (1.5%) of the single infections and 2 (1.5%) of the multiple infections contained low risk types. Statistically significant differences in the relative contribution of HPV18 were found when comparing squamous cell carcinomas with adenocarcinomas.ConclusionsHPV16 and HPV18 accounted for almost 70% of all the HPV positive ICC cases. The study provides baseline information for further evaluation on the impact of recently introduced HPV vaccines in Italy.

Abstract 5351: Human papillomavirus prevalence in bladder cancer: Molecular and pathological analysis

Abstract Objective: We preformed a molecular and pathological analysis to elucidate the prevalence of human papillomavirus (HPV) in bladder cancer. Patients and Methods: 72 cases of bladder cancer treated at Kanazawa University Hospital were enrolled in this study. As a negative control, 10 tissue samples including pathologically normal transitional cell (TC) epithelium were used. DNA was extracted from each frozen sample, and DNA quality was confirmed by amplifying the β-globin gene using PCR. Samples were tested for HPV-DNA by modified GP5+/6+ PCR, and the genotype was determined using a Hybri-Max HPV genotyping kit. Moreover, in situ hybridization (ISH) was performed to confirm presence of HPV-DNA in tumor tissue using the paraffin-embedded tissue of each sample. We compared the categorical characters such as patient's age, gender, tumor grade and tumor stage between HPV positive group and negative group. Results: Mean age of 72 patients (58 men and 14 women) was 65.2 years. 15 cases were grade1 (G1), 49, grade2 (G2) and 8, grade3 (G3). β-globin gene could be amplified by PCR test in all bladder cancer samples and normal TC epithelium. HPV-DNA was detected in 14 cases (19%) of bladder cancer samples, and was not detected in all normal TC epithelium. The grade of HPV-positive tumor indicated that 7 cases were G1 and 7 cases were G2. HPV genotypes indicated high-risk type in all cases, as follow; HPV16: 6 cases, HPV18: 4 cases, HPV33: 3 cases and HPV56: 1 case. On ISH analysis, high-risk HPV genome signals were observed in the nuclei of most of the tumor cells in all HPV positive cases. On the other hands, high-risk HPV signals were not observed in the HPV negative cases and normal TC epithelium. Type 6/11 genome signals were not shown in all samples. We compared the categorical characters between HPV positive cases and HPV negative cases. HPV-DNA was detected frequently in younger age and low grade (G1) tumor (p&amp;lt;0.05). Conclusions: HPV-DNA was detected in 19% of bladder cancer. Especially, HPV-DNA was frequently detected in low grade bladder cancer generated in the younger patients. In these cases, we demonstrated HPV-DNA was presented in the tumor tissue by ISH. We consider HPV infection can be one of etiological factors of bladder tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5351.

Human papillomavirus DNA in pterygia

Abstract Purpose To examine pterygium and normal conjunctiva tissue for the presence of human papillomavirus (HPV) and to determine the genotypes of HPV. Methods METHODS: The study involved 89 patients undergoing surgical procedures at the I Department of Ophthalmology, Medical University of Lublin, Poland. Patients were divided into 2 groups: group I with pterygium (n = 58; 51 primary, 7 recurrences) and group II with with normal conjunctiva (n=31). The material was collected during elective surgical procedures. Specimens were tested for the presence of HPV genome using polymerase chain reaction (PCR). Once the presence of HPV DNA was confirmed, 28 HPV genotypes were determined using reverse hybridisation. Results In group I, HPV DNA was identified in 16 patients (27.6%) whereas in group II ‐ in 3 cases (9.7%). Moreover, there was a statistically significant difference in the presence of HPV genome in pterygium patients compared to those with no clinical lesions of the conjunctiva (p=0.041). HPV type 16 was most frequently observed in 56% of HPV positive cases of pterygium. In 19% of cases, HPV 16 and HPV 6 co‐infections were found while in 13% ‐ HPV 18 and HPV 6 co‐infections were detected. Amongst 7 cases of recurrent pterygium, HPV 16 was detected in 2 cases. In group II, all 3 patients with HPV showed HPV 18. Conclusion In Poland, no studies concerning the presence of HPV in ocular lesions have been carried out. The group examined in our study is one of the largest populations of patients with pterygium studied for the presence of the HPV genome worldwide. Our findings show that HPV is likely to play a synergistic role in the multi‐stage process of the development of pterygium, although it is not necessary to induce this condition.

High prevalence of human papillomavirus 16 in penile carcinoma.

In order to analyze the incidence and prevalence of Human Papillomavirus (HPV) in penile carcinoma, we studied 49 patients with penile carcinoma. Formalin-fixed, paraffin-embedded tissue samples were collected from 64 samples of penile carcinoma from the Hospital General Universitario (Albacete, Spain). Cases were histologically classified and the polymerase chain reaction (PCR) method was used to detect the presence of HPV. Two sets of consensus primers were used, the My09/My11, and the GP5+/GP6+. All positive cases were sequenced in order to establish the implicated genotype. Our results showed that 38 of the 49 cases were positive for HPV (77,5%). HPV16 appeared in 32 (84,2 %) of the 38 positive cases and HPV18 in 4 (10,5%). Our data demonstrate that the My09/My11 primers are more sensitive than GP5+/GP6+ primers, although the combination of the two sets of primers notably increased the total number of HPV positive cases detected.

Frequency of human papillomavirus infection in oesophageal squamous cell carcinoma in Iranian patients

Human papillomavirus (HPV) is 1 of the possible aetiological factors in the development of oesophageal squamous cell carcinoma (ESCC). We aimed to study the role of HPV in ESCC. 140 cases of ESCC were analysed for the HPV DNA by polymerase chain reaction (PCR) using GP5+/GP6+ primers for L1 open reading frame (ORF) to amplify a 150 bp segment of HPV L1 ORF. This region was subsequently sequenced to identify the type of HPV. Of the 140 patients enrolled to our study 50.7% were female and 49.3% were male, aged between 20 and 81 y. 33 tumour specimens (23.6%) and 12 (8.6%) non-involved tumour margins were HPV positive. From HPV positive tumour cases 36% were positive in tumour margins. The HPV positive cases were 21.7% male and 25.3% female. There is no correlation between presence and types of HPV with patients' gender and age. The frequency of HPV subtypes in tumoural regions was as follows: HPV-16, 60.6%; HPV-18, 30.3%; HPV-33, 6.1%; and HPV-31, 3%. We found only HPV-16 in tumour margins. Our results are consistent with HPV studies conducted in other high-risk areas for ESCC and provided further evidence to support a causal association of HPV infection with ESCC.

TNFα–308G/A Polymorphism as a Risk Factor for HPV Associated Cervical Cancer in Indian Population

Background: Investigation of the potential association of single nucleotide polymorphisms (SNPs) at –308 G/A and –238 G/A of Tumor necrosis factor α (TNFα) with susceptibility to HPV-16 associated cervical cancer in Indian women. Methods: The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFα promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection. Results: The frequency of –308 A allele in TNFα was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p < 0.01), with an odds ratio of 2.7 (95% CI = 1.41–5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p < 0.01; OR = 3.1; 95% CI = 1.60–6.03). No such association was found for TNFα–238 (G/A) polymorphism with the risk of development of cervical cancer. Conclusion: It suggests that SNP at –308 (G/A) of TNFα promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.

Human papillomavirus in lung carcinomas among three Latin American countries

The presence of human papillomavirus (HPV) genome in lung carcinomas has been reported worldwide but its frequency varies from country to country. We examined HPV genome in 36 lung carcinomas, consisting of 14 squamous cell carcinomas, 13 adenocarcinomas, and 9 small cell carcinomas, collected from Colombia, Mexico and Peru. PCR analysis using GP5+/GP6+ primers, combined with Southern blot hybridization, found the presence of HPV genome in 10 (28%) of 36 cases. This percentage is similar to the value of 22% reported by Syrjänen, who conducted a meta-analysis of nearly 2500 lung carcinomas examined to date. Genotype analysis revealed that the most predominant genotype was HPV-16 (7 cases), followed by HPV-18 (2 cases) and HPV-33 (1 case). HPV-16 was more frequently found among female than male cases (P=0.008) but was not detected in any adenocarcinoma cases. On the other hand, HPV-18 and HPV-33 were detected only among male cases. These HPV genotypes were detected only in adenocarcinomas, and all the HPV genotypes detected in this histological type were HPV-18 or HPV-33. The frequency of HPV-16 positive cases among all the HPV positive cases differed in the sexes (P=0.033) and differed in the three histological types (P=0.017). The presence of HPV tended to be more frequent in well-differentiated tumors when squamous cell carcinomas and adenocarcinomas were combined. However, it was not statistically significant (P=0.093). Neither p16 nor p53 expression in carcinoma cells was related to the proportion of HPV-positive cases. In conclusion, high-risk HPV DNA was detected in 28% of lung carcinomas. The predisposition of HPV-16 to female cases and to non-adenomatous carcinomas warrants further investigation.

High-risk human papillomavirus DNA testing: A marker for atypical glandular cells

Cervical/endocervical cytology screening has decreased morbidity and mortality, and implementing adjunctive human papilloma virus (HPV) DNA testing for atypical squamous cells of undetermined significance has improved the specificity for detecting premalignant squamous lesions. Currently, there are no guidelines to perform HPV DNA testing on cervical/endocervical ThinPreps with atypical glandular cells (AGC). To assess the potential role of HPV DNA testing on AGC cases, Hybrid Capture 2 (Digene Corp.) testing was performed on 144 cervical/endocervical AGC specimens. One hundred three of 144 cases had follow-up; 60/103 (58.3%) were high-risk HPV negative and 43/103 (42.3%) were high-risk HPV positive. Of 43 HPV-positive patients, 37 had adenocarcinoma in situ (AIS), atypical squamous cells of undetermined significance (ASCUS), or cervical squamous intraepithelial neoplasia, while only one patient without high-risk HPV had a squamous intraepithelial neoplasia. Furthermore, most high-risk HPV positive AGC cases harbored high-grade squamous intraepithelial lesion (HSIL) rather than AIS. Our data support HPV DNA testing of all AGC specimens to detect cervical, especially squamous, neoplasia.

Polymorphism at codon 72 of p53, human papillomavirus, and cervical cancer in South India

It has been suggested that host genetic factors play a role in human papillomavirus (HPV)-associated tumorigenesis, although the issue continues to be a focus of much debate. Previous studies have reported that a common polymorphism of the wild type p53 gene at codon 72 of exon 4 (Arg/Arg) is associated with a sevenfold increased risk of HPV-associated cancer compared to Arg/Pro and Pro/Pro polymorphisms. In vitro studies also suggested that the Arg/Arg polymorphism was much more susceptible to HPV 16 E6-mediated degradation as compared to other allelic forms. Subsequent studies published since this initial report indicated geographical differences with respect to the role of Arg/Arg polymorphism in increasing the risk of HPV-associated cervical cancer. In this study we analyzed leukocyte DNA from a total of 421 subjects for the Arg/Arg, Arg/Pro or Pro/Pro p53 polymorphisms at various stages of the cervical tumor progression spectrum, using allele-specific PCR. All subjects were from the Thiruvananthapuram District of South India. HPV genotyping was done for all subjects using either DNA extracted from cervical biopsies or exfoliated cervical cells. All subjects were grouped on the basis of both of cyto-pathology and HPV status. The distribution of p53 genotypes was not significantly different in all study groups (HPV positive vs HPV negative and cases vs controls comparisons). Homozygosity for Arg/Arg was not associated with increased risk for cervical cancer. We find no evidence for any association between homozygosity for p53 arginine with either cervical dysplasia, cervical carcinoma or HPV infection in the population from South India.

Prevalence of high-risk human papilloma virus types and its association with P53 codon 72 polymorphism in tobacco addicted oral squamous cell carcinoma (OSCC) patients of Eastern India.

Human papillomavirus (HPV) infects the squamous epithelial cells of oral cavity and cervix leading to formation of warts that develops into the cancer. Human papillomavirus (HPV)-16 and 18 encode E6 oncoprotein, which binds to and induces degradation of the tumour suppressor protein p53. A common polymorphism of p53, encoding either proline (Pro) or arginine (Arg) at position 72, affects the susceptibility of p53 to E6 mediated degradation in vivo. Oral cancer is a pressing problem in India due to the widespread habit of chewing betel quid, which plays an important role in etiology of this disease. In the present study an attempt has been made to analyze the genetic predisposition of the Indian population to HPV infection and oral carcinogenesis. In our study a total of 110 cases of Oral Cancer highly addicted to betel quid and tobacco chewing are analyzed for HPV 16/18 infection and its association with polymorphism at p53 codon 72. Of these a total number of 37 patients (33.6%) have shown the presence of HPV, among which the presence of HPV-16, 18 and 16/18 coinfection is 22.7%, 14.5% and 10%, respectively. Our results also indicate that the p53 codon 72 genotype frequencies in Indian Oral Cancer patients are 0.55 (Arg) and 0.45 (Pro) as per Hardy-Weinberg equilibrium. In our study, striking reduction in Pro/Pro allele frequency has been found in HPV positive cases, indicating Arg/Arg genotype to be more susceptible to HPV infection and oral carcinogenesis.