Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer.

Background & objectives: High-risk human papilloma virus (HR-HPV) infection and its integration in host genome is a key event in malignant transformation of cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to analyze if viral load and physical state of the virus correlated with each other in the absence of other confounding variables and examined their potential as predictors of progressive cervical lesions. Methods: Both, viral load and integration status of HPV16 were determined by real time URR PCR and estimation of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30) and high grade (HSIL, 30), and invasive carcinoma, (squamous cell carcinoma SCC, 70) cases. Results: Investigation of DNA samples revealed a gradual increase in HPV16 viral load over several magnitudes and increased frequency of integration from LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions in monotypic HPV16-infected cervical tissues. In a substantial number of precancer (11/60) and cancer cases (29/70), HPV16 was detected in concomitant mixed form. The concomitant form of HPV16 genome carried significantly higher viral load. Interpretation & conclusions: Overall, viral load and integration increased with disease severity and could be useful biomarkers in disease progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.

Evaluation of adefovir & lamivudine in chronic hepatitis B: correlation with HBV viral kinetic, hepatic-necro inflammation & fibrosis.

Background & objectives: Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. Methods: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. Results: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histotogy activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. Interpretation & conclusions: Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.

HPV & HPV vaccination: Issues in developing countries.

Cervical cancer is the second-most common cancer in women worldwide causing most cancer related deaths in women in developing countries including India. The most predominant etiological factor for cervical cancer is persistent infection of certain high-risk types of human papillomaviruses (HR-HPVs), while low-risk types are associated with benign cervical lesions and genital warts. In India, the most common (98%) oncogenic types are HPV types 16 and 18 with HPV 16 exclusively (80-90%) prevalent. Two recently developed virus-like particle (VLP) based prophylactic HPV vaccines, quadrivalent Gardasil (HPV 16/18/6/11) and Cervarix (HPV 16/18) offer great promise. Several other therapeutic vaccines are also in clinical trials and are yet to establish their efficacy. The use of already developed VLP vaccines in resource-poor regions is limited by several factors, most importantly the high cost of the vaccine. Therefore efforts are being made in India to develop cost-effective second-generation vaccines. Besides cost, there are several socio-cultural and ethical issues involved with the implementation of already developed vaccines including the acceptability of HPV vaccination by preadolescent girls and their parents in India.

Anti-human papillomavirus therapeutics: Facts & future.

Even after 25 years of establishing Human Papillomavirus (HPV) as the causative agent for cervical cancer, effective treatment of HPV infection still unavailable. Comprehensive efforts especially for targeting HPV infection have been made only in recent years. Conventional physical ablation of HPV-induced lesions such as cryo-therapy, photo-therapy, LEEP, laser cone-biopsy and localized radiotherapy are shown to be effective to some extent in treating localized lesions where the removal of diseased tissue is associated with removal of transforming keratinocytes harboring HPV. Apart from currently available prophylactic vaccines which prevent the viral entry and should be given prior to viral exposure, several attempts are being made to develop therapeutic vaccines that could treat prevailing HPV infection. In addition, immunomodulators like interferons and imiquimod that have been shown to elicit cytokine milieu to enhance host immune response against HPV infection. Also, antiviral approaches such as RNA interference (RNAi) nucleotide analogs, antioxidants and herbal derivatives have shown effective therapeutic potential against HPV infection. These leads are being tested in pre-clinical and clinical studies. Present article provides a brief overview of conventional therapies for HPV-associated diseases. Potential of non-ablative anti-HPV treatment modalities that could prove useful for either elimination of HPV in early stages of infection when the virus is not integrated into the host cell genome or suppression of the expression of viral oncogenes that dysregulate the host cell cycle following transformation is discussed.

Infection of human papillomaviruses in cancers of different human organ sites.

Clinico-epidemiological and molecular studies have established the casual link between Human Papillomavirus (HPV) infection and cervical cancer as also association of HPV infection with several other cancers. In India, cervical cancer is a leading cancer among women and almost all cases of cervical cancer show prevalence of High Risk (HR)-HPV infection. HPV has been also detected in a significant proportion of oral, esophageal, anal, vaginal, vulvar, and penile cancer and in a small percentage of lung, laryngeal, and stomach cancer in India. Due to lack of organized HPV screening program, insufficient infrastructure and trained manpower and inadequacy in cancer registries, there are not much data available on the countrywide HPV prevalence and its type distribution in different cancers in India. Forthcoming introduction of recently developed HPV vaccines in India given a new urgency to know the prevalence and distribution of various HPV types in different organ sites for the management and monitoring of vaccination program and its impact on prevalence of other cancers. This review, summarizes studies on the prevalence of HPV infection in cancers of different organ sites in India.

Seroprevalence of hepatitis D virus in patients with hepatitis B virus-related liver diseases.

BACKGROUND AND OBJECTIVE: Several reports indicated a declining trend in the occurrence of hepatitis D virus (HDV) infection in some geographical areas. However, no study has been conducted in India to evaluate whether a similar epidemiological change is occurring in this part of the world. The present study was undertaken to evaluate the seroprevalence of HDV in patients with hepatitis B virus (HBV) related liver diseases attending a Government hospital in New Delhi, and to assess any change in its epidemiology by comparing the results with seroprevalence figures reported in the past. METHODS: A total of 123 patients with HBV-related liver diseases comprising 32 cases of acute viral hepatitis (AVH), 5 of fulminant hepatic failure (FHF), 37 of chronic hepatitis (CH), 46 of cirrhosis and 3 of hepatocellular carcinoma (HCC). All patients were evaluated for the presence of delta antibodies using commercially available ELISA kits. Both IgM and IgG anti-delta assays were performed to differentiate between active and convalescent infection. RESULTS: The mean age of the patients was 35.6 +/- 3.3 yr with a male : female ratio of 11:5. Of the 123 patients, serological evidence of delta virus infection was seen in 13 subjects (10.6%); 9 (7.3%) had evidence of past infection (IgG positive, IgM negative) and the remaining 4 (3.3%) recent infection (IgM anti-delta antibody positive). Evidence of HDV infection in acute viral hepatitis, fulminant hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma groups was found in 3.1, 20, 8.1, 15.2 and 33.3 patients, respectively. INTERPRETATION AND CONCLUSION: Our results suggest that delta infection may not be very common in Indian patients with HBV-related liver diseases. It is also possible that HDV epidemiology in this part of the world may be undergoing a transition towards decreasing prevalence.