Type-specific human papillomavirus prevalence in cervical intraepithelial neoplasia and cancer in Iran.

In Iran, human papillomavirus (HPV) vaccination is not currently included in the national vaccination program and there are no comprehensive approaches to cervical screening program. Regional data on distribution of HPV types in women is important to predict the impact of current HPV vaccines. Although several studies on distribution of HPV types in cervical precancer and cancer have been conducted in Iran, in most of them HPV positive samples were subjected to specific-primer genotyping (mainly 16 and 18), and leaving the other HPV genotypes almost undetermined. Therefore, the present study aimed to investigate the distribution of HPV types in cervical neoplasia from West and Northwest of Iran. A total of 112 women with atypia, cervical intraepithelial neoplasia, and invasive cervical cancer were included. A PCR assay was performed in all samples to detect the presence of the HPV genome using the GP5+/6+ L1 consensus primer set. All HPV positive samples were subjected for sequencing. In overall, HPV prevalence was 20% in atypica, 44.5% in cervical intraepithelial neoplasia I, 92.3% in cervical intraepithelial neoplasia II-III, and 98.2% in invasive cervical cancer. The most frequent HPV type was HPV 16 (79.2%), which was followed by HPV types 18, 6, and 33 at the frequencies of 6.5%, 5.1%, and 2.7%, respectively. The least HPV types were found to be 31, 45, 53, 58, and 66. In conclusion, this study shows that the current HPV vaccines could have great impact to reduce the burden of cervical cancer in Iran.

Human papillomavirus type 16 lineage analysis based on E6 region in cervical samples of Iranian women.

It is suggested that distinct HPV 16 variants differ in oncogenic potential and geographic distribution. As such, understanding the regional variants of HPV 16 would be of great importance for evolutionary, epidemiological and biological analysis. In this regard, the sequence variations of E6 gene were investigated to characterize more common variants of HPV 16 in normal cells, premalignant and malignant lesions of the cervix. In total, 106 isolates of HPV 16 were analyzed by PCR and sequencing. Overall, two different lineages (A and D) were identified. Lineage D comprised 70.7% of samples and the remaining 29.3% belonged to lineage A. Regarding to cytology/histology, lineage D was dominant in both normal+CIN I-II and CIN III+ICC groups as it was detected in 80% and 66.2% of cases, respectively. The comparison of the lineages between different groups (35 normal+CIN I-II samples and 71 CIN III+ICC samples) revealed that lineage A is more prevalent in cervical cancer cases (7 (20%) vs. 24 (33.8%)) although the difference observed did not reach statistical significance (p=0.07). In conclusion, our findings confirm that HPV lineages A and D are more prevalent in Iran, with the lineage D as the most dominant in all studied groups.

Type-Specific Human Papillomavirus Prevalence in Iranian Women with Normal Cervical Cytology: The Impact of Current HPV Vaccines.

OBJECTIVE: Human papillomavirus (HPV) vaccination is currently not included in the national vaccination program in Iran. Regional data on the distribution of HPV types in women are important as they can predict the impact of currently available vaccines and help health policy makers to consider all the possibilities with regard to HPV vaccination. METHODS: A total of 1,218 Iranian women with normal cervical cytology were included in this study. The presence of the HPV genome was investigated in all specimens by PCR assay, and all HPV-positive samples were genotyped. RESULTS: Totally, HPV was detected in 88 samples (7.2%). According to different geographical regions, the HPV prevalence varied: the highest HPV prevalence was observed in the North (11.7%) and the lowest in the Center (4.5%) of Iran, and this difference reached a statistically significant level (p < 0.05). In this study, the most frequent HPV types were HPV 16, 18, 66, and 11, representing 63.8% of all HPV infections. CONCLUSION: Based on this study, it is estimated that HPV vaccines could have a great impact on the prevention of cervical cancer in Iran. This study highlights the necessity of introducing educational programs in high schools, robust screening programs, and vaccination in Iran.

The prevalence of human papillomavirus infection in Iranian patients with sinonasal inverted papilloma.

BACKGROUND: Inverted papilloma (IP) is an uncommon disease which arises in the mucosal membrane of the nasal cavity and paranasal sinus. It has been proposed that human papillomavirus (HPV) is the causal agent in the pathogenesis of IP and plays a key role in the progression from benign IP to malignancy. As there are no prior studies that focus on an Iranian population, this study intended to characterize the prevalence of HPV types in benign and malignant forms of IP. METHODS: In this retrospective study, we included a total of 40 IP patients [37 benign IP and 3 IP/squamous cell carcinoma (SCC)] who were referred to Amiralam Hospital in Tehran from 2004-2006. RESULTS: HPV was detected in 18.9% and 100% of IP and IP/SCC cases, respectively. In all HPV positive cases of IP and IP/SCC cases, HPV6/11 and HPV16/18 were detected, respectively. Therefore, HPV types were different between the IP and IP/SCC patients, and this difference was statistically significant (p = 0.002). CONCLUSION: This study suggests that HPV6 and 11 may be involved in the development of IP, but HPV16 and 18 likely play an important role in the progression from benign to malignant form of IP.

Prevalence of BK viremia in Iranian hemodialysis and peritoneal dialysis patients.

BACKGROUND: BK virus (BKV) is a common human polyomavirus which infects up to 90% of the general population with little clinical significance and with various epidemiological patterns of infection. Immune suppression is considered the main risk factor for BKV reactivation. Owing to their impaired cellular and humoral immunity, patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) are at high risk of infectious diseases such as BKV infection. BKV presents with different distributions in different populations. This study aimed to determine the prevalence of BKV in Iranian patients with chronic renal disease undergoing HD and PD. METHODS: Sixty-three HD patients and 33 PD cases from the main dialysis units in Tehran, Iran, were enrolled in the study. BK viremia was determined by qualitative polymerase chain reaction in all subjects. RESULTS: Sixty-three cases under HD (mean age 59.3 ± 14.5 years) and 33 subjects on PD (mean age 53.7 ± 13 years) were enrolled in the study. The mean duration of HD was 59.1 ± 53.8 months and the dialysis interval was three times a week. In the PD group, the mean duration of dialysis was 38.9 ± 35.2 months. The prevalence of BK viremia was 3.03% in PD and 0% in HD subjects. CONCLUSIONS: This study showed a low rate of BK viremia in chronic renal disease patients undergoing HD or PD. Differently from other studies in various populations, our results demonstrated low or absent BKV replication in Iranian dialysis patients, highlighting the varying epidemiological pattern of BKV distribution.

Meta-analysis of type-specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination.

To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta-analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta-analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta-analysis highlights the necessity of introducing vaccination program in Iran.

Lack of human papillomavirus DNA in colon adenocarcinama and adenoma.

BACKGROUND: Human papilloma viruses (HPV) have been detected in several types of cancers. Over the last few years, a possible correlation between HPV infection and colon cancers has been suggested. The aim of this study was to assess the presence of HPV-DNA in colon adenocarcinomas and adenomas to describe the relationship of HPV infection with these pathologic features. MATERIALS AND METHODS: The study included formalin-fixed and paraffin-embedded tissue samples of 70 patients with colon adenocarcinoma and 30 patients with adenoma (as study group) and 30 tumor adjacent tissues (as control). HPV-DNA was purified and first amplified through MY09/MY11 and GP5+/GP6+ primers. Subsequently, for more precision, another PCR was performed using PGMY09/11 L1 consensus primer system. RESULTS: All tested adenocarcinomas and adenomas as well as normal tumor adjacent tissues were negative for all types of HPV in two PCR assays. CONCLUSION: Our results do not support the relationship between HPV infection and colon carcinoma or adenoma. Attributing a role to the HPV in the etiology of colon carcinogenesis will require further studies.

Human papillomavirus burden in different cancers in Iran: a systematic assessment.

Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investigation covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.

Evaluation of the thermal stability of a novel strain of live-attenuated mumps vaccine (RS-12 strain) lyophilized in different stabilizers.

The stability of live-attenuated viral vaccines is important for immunization efficacy. Here, the thermostabilities of lyophilized live-attenuated mumps vaccine formulations in two different stabilizers, a trehalose dihydrate-based stabilizer and a stabilizer containing sucrose, human serum albumin and sorbitol were investigated using accelerated stability tests at 4°C, 25°C and 37°C at time points between 4h (every 4h for the first 24h) and 1 week. Even under the harshest storage conditions of 37°C for 1 week, the 50% cell culture infective dose (CCID50) determined from titrations in Vero cells dropped by less than 10-fold using each stabilizer formulation and thus complied with the World Health Organization's requirements for the potency of live-attenuated mumps vaccines. However, as the half-life of the RS-12 strain mumps virus infectivity was lengthened substantially at elevated temperatures using the trehalose dihydrate (TD)-based stabilizer, this stabilizer is recommended for vaccine use.

Development of a stable insect cell line constitutively expressing rotavirus VP2.

An insect High-Five cell line was generated constitutively and stably expressing the VP2 protein of rotavirus RF strain leading to the formation of core-like particles. The integration of the VP2 gene was confirmed by PCR, Real-time PCR and Southern blot, and the protein expression was confirmed by Western blot and immunofluorescence microscopy. Integrity and self assembly of VP2 as core-like particles was demonstrated by electron microscopy. The High-Five cell system stably expressing rotavirus core-like particles can be applied to the study of viral protein structure and functions; it may be useful for vaccine development, gene therapy and drug delivery.

Molecular characterization analysis of the outer protein layer (VP7) from human rotavirus A genotype G1 isolate identified in Iran: implications for vaccine development.

The full open reading frame of the outer protein layer VP7 from an isolate of human rotavirus identified in 2010 in an Iranian child admitted to hospital with gastroenteritis was amplified from a clinical stool specimen and subjected to molecular characterization. Genetic and phylogenetic analyses indicated that the analyzed gene falls into the G1 genotype forming a sub-cluster with sequences recently identified in Iran and geographically distant countries. Such results were confirmed by protein sequence alignment, showing a highly conserved "G1-like?? amino acid sequence pattern within the known three main immunodominant regions. These results are extremely relevant in a perspective of vaccine development. Indeed, the present study confirms that the A group G1 genotype is the most prevalent Rotavirus circulating in Iran and supports the development of G1 genotype-based rotavirus vaccine for this country.

Molecular epidemiology of human herpesvirus 8 variants in Kaposi's sarcoma from Iranian patients.

Kaposi's sarcoma (KS) is a rare cancer in Iran and there is no epidemiological and molecular information about HHV-8 variants circulating among the Iranian population. In this study HHV-8 sequences have been analyzed in 43 cutaneous KS biopsies from Iranian patients mainly affected by classic KS. DNA samples were subjected to PCR amplification of HHV-8 ORF26, T0.7 and K1 followed by direct nucleotide sequencing and phylogenetic analysis. The analysis of ORF26 showed that 30 (69.8%) and 13 (30.2%) samples belonged to subtypes A/C and K, respectively. In general, the clustering of HHV-8 T0.7 variants paralleled that of ORF26. Genotyping of K1 sequences showed that the majority of samples (39 out of 41) fall into the large C clade with only 2 belonging to the A clade. In conclusion, HHV-8 variants identified among classic Iranian KS are largely related to Eurasian genotypes previously identified in KS from Mediterranean, Middle East, and East Asian regions.

The role of Human papilloma virus (HPV) genotyping in recurrent respiratory papillomatosis in Rasoul Akram Hospital.

BACKGROUND: The most common laryngeal mass in children is recurrent respiratory papillomatosis (RRP). Studies have attempted to correlate viral typing and its aggressiveness. METHOD: 29 patients with histologically confirmed RRP enrolled in adjuvant therapies. Patients underwent several surgical interventions. RESULTS: HPV genotyping demonstrated 45% HPV-6 and 55% HPV-11. The mean age at the first surgical intervention was 52.39 months (SD=102.28) (range from 4 months to 426 months). The mean number of surgical intervention was 10.39 (SD=7.76) (range from 2 to 30). The mean time of surgical intervals was 4.63 months (SD=4.02) (range from 2 to 24 months). In fourteen patients (48%) tracheotomy was done. All patients who had tracheotomy received alpha-interferon. One of our cases was a male who had pulmonary extension with HPV-6. CONCLUSION: A review of patients with RRP was regarding to HPV genotyping and need for adjuvant therapy and tracheostomy. Mean number of surgical procedure was 10/40 and nearly fourteen patients (48%) need to tracheotomy. The clinical differences between HPV6 and HPV11 disease may not be accurately predictable. Patients with less age and with HPV-11 seemed to have more severe problems, but these differences were not statistically significant which needs much more investigations for reasonable starting point of evaluation for these differences.

The role of human papillomavirus infection in prostate carcinoma.

Human papillomavirus (HPV) infections are associated with benign and malignant lesions of the female and male anogenital tract. Currently the possible role of HPV infections in prostate carcinogenesis is a subject of great controversy. In this study we aimed to investigate the role of HPV infection in prostate carcinoma (PCa). The study included formalin-fixed paraffin-embedded tissue samples of 104 primary prostate adenocarcinoma cases and 104 control tissues of benign prostatic hyperplasia (BPH). HPV-DNA was purified and amplified through MY09/MY11 and GP5(+)/GP6(+) primers and subsequently subjected to sequencing. HPV-DNA was found in 13 of 104 (12.5%) PCa and 8 of 104 (7.7%) BPH samples. High-risk HPVs were detected in 10 of 13 (76.9%) PCa and 5 of 8 (62.5%) BPH samples with positive HPV-DNA. Low-risk HPVs were detected in 3 of 13 (23.1%) PCa and 3 of 8 (37.5%) BPH specimens with positive HPV-DNA. There was no significant difference between PCa and BPH specimens regarding HPV-DNA presence or the detection of high-risk and low-risk types of HPV. Our data do not support the role of HPV infection in prostate carcinoma. Further studies are required to elucidate the role of HPV infection in human prostate carcinogenesis.

Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients.

BACKGROUND: Several studies have reported an increasing number of therapeutic failures with antiretroviral drugs in HIV-infected patients. The emergence of viral-resistant strains is a major problem for the medical management of infected individuals. The aim of this study is to determine viral subtypes and drug-resistance mutations among antiretroviral-treated HIV-infected patients. METHODS: A total of 42 antiretroviral-treated but still viremic HIV-infected patients were enrolled. The HIV pol regions were amplified and sequenced to determine subtypes and antiretroviral-resistant mutations. RESULTS: The subtype distribution was 48% A/D recombinants, 43% subtype B, 5% subtype A and 5% CRF01-AE recombinants. Drug-resistant mutations were most common in subtype B (53%) and A/D recombinant strains (44%). Virus samples from 19% of participants had no drug-resistant mutations; 2, 2 and 76% of samples carried one, two and at least three drug-resistant mutations, respectively. The prevalence of nucleoside transcriptase inhibitor mutations was 76%, with M184V and L74V present in 60 and 38% of samples, respectively. The prevalence of nonnucleoside transcriptase inhibitor mutations was 74%, with P225H present in 55% of study specimens. The prevalence of protease inhibitor mutations was 45%, with major mutation L90M seen in 33% and minor mutation A71V in 36% of samples. Of note, the P225H and A71V are 'minor' drug-resistance mutations conferring only minimal drug-resistance phenotypes in the absence of major mutations. CONCLUSION: Our study found a high prevalence of drug-resistant mutations in Iranian HIV-infected patients. Our data support the need for continued surveillance of resistance patterns to help guide therapeutic approaches and limit transmission of these variants.

Prevalence of various human papillomavirus (HPV) genotypes among women who subjected to routine Pap smear test in Bushehr city (south west of Iran) 2008-2009.

BACKGROUND: Some genotypes of human papillomaviruses can infect the genital tract and they are important infectious agents which their oncogenicity is regardable. Thus the aim of this study was to determine the prevalence of various genital human papillomaviruses (HPV) among women being subjected to routine pap smear test in Bushehr city of Iran. RESULTS: Based on the collected data, 11(5.5%) samples were detected positive for HPV DNA and 189(94.5%) samples out of 200 samples were detected negative for HPV DNA. Meanwhile 4(2%) samples detected positive for HPV DNA by PCR were detected positive for HPV by pap smear test as well. On the other hand 5 samples which were detected positive for HPV by pap smear test didn't have HPV DNA after being tested by PCR method. Among the 11 positive samples 7 samples were identified as HPV-16, 3 samples were HPV-18 and one was HPV-53. CONCLUSION: Regarding the prevalence of highly carcinogen genotypes of HPV in our study determination of genital HPV prevalence among the normal population of women of Bushehr city is recommended.

Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study.

We performed a pilot surveillance study on transmitted HIV drug resistance (TDR) in Iran, with specimens collected and stored as dried blood spots (DBS). The protease region and relevant positions in the reverse transcriptase region of the pol gene were sequenced to detect mutations known to be associated with resistance to drugs in standard first-line regimens. Seventy-three specimens were collected, with 39 (53%) specimens yielding sequence from both protease and at least part of RT. Specimens were almost exclusively HIV-1 subtype CRF 35_A1D based on pol sequencing. Mutations were restricted to RT, with D67DG and V75AV each seen in a single specimen. An atypical protease inhibitor mutation, I47M, appeared at a resistance-associated position in protease from a single specimen. These preliminary data showed that the rate of transmitted drug resistance in Iran, within the areas sampled, was 5.1% (2/39). However, the small sample size makes this figure only an approximation. Due to the sampling strategy and resulting small sample size, we were unable to accurately calculate TDR rates for individual areas using the WHO HIV drug resistance threshold survey method. Increasing the sample size and improving the yield from DBS would improve the accuracy of drug resistance surveillance and facilitate wider application of this methodology in Iran.

Surface gene mutations of hepatitis B virus among high-risk patients with occult hepatitis B virus infection.

Surface gene mutants of hepatitis B virus (HBV) have been reported in a variety of patient groups. Because of limited data regarding these mutations in patients with occult HBV infections; we aimed to determine these mutations among high-risk patients with occult HBV infection. The presence of HBV-DNA was determined in patients with isolated anti-HBc by real-time polymerase chain reaction (PCR). Then, surface gene region was amplified by nested PCR and mutations were analyzed after sequencing. The mutations that resulted in nonfunctional hepatitis B surface antigen (HBsAg) were insertion of single nucleotide in 2 cases, which causes frameshift and single-nucleotide replacement, and premature stop codons at Leu15 and Gly10 in the other 2 cases. Amino acid substitution at amino acid position 207(S207N) was found in the other isolates. Our study suggested that "a" region mutations did not play a major role in HBsAg detection, and other genetic and nongenetic factors may be responsible for failure to detect HBsAg by routine laboratory tests.

Hepatitis B virus genotype in Iranian patients with hepatocellular carcinoma.

OBJECTIVE: Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV appears to be the most common cause of HCC in Iran. To date, no study has been carried out on the HBV genotype in Iranian HCC patients. This study was undertaken to determine the HBV genotype in Iranian patients with HCC. METHODS: Paraffin-embedded tissue samples from 40 patients (31 males and nine females) with HBV-associated HCC were collected from different pathology centers during 2000-2007. Genotyping of HBV was performed by nested PCR-mediated amplification of the target sequence. PCR products were sequenced, and the genotype of each HBV sequence was determined by comparison with sequences of known genotypes in the GenBank. A phylogenetic tree was constructed. RESULTS: Phylogenetic analysis revealed that all of the HBV isolates were clustered in genotype D. CONCLUSIONS: Our results concur with other reports from Iran, all showing that genotype D is the only detectable genotype in the different clinical forms of HBV infection in this country.

Detection of hepatitis G virus envelope protein E2 antibody in blood donors.

OBJECTIVES: The frequency of hepatitis G virus exposure in blood donors varies between 2.5% in Japan to 24.2% in Poland. Therefore there is a geographic difference in distribution of hepatitis G virus (HGV) in the world. We aimed to determine the frequency of HGV exposure in Iranian blood donors. METHODS: Blood samples from 478 Iranian volunteer blood donors were tested. Positive anti-E2 samples were tested for HGV RNA by reverse transcriptase polymerase chain reaction (RT PCR) using primers derived from the NS5A region of the viral genome. RESULTS: Of the 478 donors enrolled in our study, five (1%) were positive for anti-E2. Only one donor out of a total of three HBsAg-positive donors was co-infected with HGV, but we did not find HGV and HCV co-infection in our subjects. HGV RNA was not observed in the five anti-E2-positive subjects. We did not find HGV viremia and antibody at the same time. CONCLUSION: A low frequency of HGV exposure in blood donors was found in this study. We did not observe co-infection of HGV with HCV in our subjects, supporting the theory that although the parenteral route is the most effective means of transmission, other routes such as sexual contact and intra-familial contact may also play a role in HGV transmission.