Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single ...dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to ‘no vaccination’.
In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10–18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702.
Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women.
Our results indicate that a single dose of quadrivalent HPV vaccine is immunogenic and provides lasting protection against HPV 16 and 18 infections similar to the three- and two-dose vaccine schedules, although the study suffer from some limitations. Data on long term protection beyond 7 years against HPV infection and cervical precancerous lesions are needed before policy guidelines regarding a single dose can be formulated and implemented. Significant and long-lasting protective effect of a single dose can be a strong argument to introduce one dose of the HPV vaccine in many low income countries where the current standard of care for cervical cancer prevention is ‘no intervention’.
North East Region in India is showing a peculiar type of cancer incidence pattern. This is an attempt to get a clear picture of cancer in NE India, the gaps in providing cancer care, and a way ...forward for a healthier NE. For this purpose, a desk review was undertaken along with secondary data analysis in 2018. In NE, the survival rate is comparatively very low, with higher proportion of distant metastasis cases at diagnosis. Even worse, the NE region lacks required infrastructure with respect to specialized treatment facilities, human resources, etc., In view of high burden of the disease with very limited resources, a multidisciplinary, multidimensional, and multilevel approach are needed to protect this vibrant region from becoming the cancer hub.
Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the ...disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11-2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25-0.65,p<0.001 and OR = 0.51;95%CI = 0.33-0.78,p = 0.002 respectively). In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His), SULT1A1 213GG (Arg/Arg) or AA (His/His) and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33-10.55,p = 0.006), whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg) and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15-7.51,p = 0.01). MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His) and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His) with testing balance accuracy (TBA) of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with SULT1A1 Arg213His and EPHX1 Tyr113His in smokers and SULT1A1 Arg213His with GSTP1 Ile105Val and CYP1A1*2C in nonsmokers. These results identified distinct gene-gene and gene environment interactions in smokers and non-smokers, which confirms the importance of multifactorial interaction in risk assessment of lung cancer.
Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to ...compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier.
Betel Quid (BQ) chewing independently contributes to oral, hepatic and esophageal carcinomas. Strong association of breast cancer risk with BQ chewing in Northeast Indian population has been reported ...where this habit is prodigal. We investigated genomic alterations in breast cancer patients with and without BQ chewing exposure. Twenty six BQ chewers (BQC) and 17 non BQ chewer (NBQC) breast cancer patients from Northeast India were analyzed for genomic alterations and pathway networks using SNP array and IPA. BQC tumors showed significantly (P<0.01) higher total number of alterations, as compared with NBQC tumors, 48 ± 17% versus 32 ± 25 respectively. Incidence of gain in fragile sites in BQC tumors were significantly (P<0.001) higher as compared with NBQC tumors, 34 versus 23% respectively. Two chromosomal regions (7q33 and 21q22.13) were significantly (p<0.05) associated with BQC tumors while two regions (19p13.3-19p12 and 20q11.22) were significantly associated with NBQC tumors. GO terms oxidoreductase and aldo-keto reductase activity in BQC tumors in contrast to G-protein coupled receptor protein signaling pathway and cell surface receptor linked signal transduction in NBQC tumors were enriched in DAVID. One network "Drug Metabolism, Molecular Transport, Nucleic Acid Metabolism" including genes AKR1B1, AKR1B10, ETS2 etc in BQC and two networks "Molecular Transport, Nucleic Acid Metabolism, Small Molecule Biochemistry" and "Cellular Development, Embryonic Development, Organismal Development" including genes RPN2, EMR3, VAV1, NNAT and MUC16 etc were seen in NBQC. Common alterations (>30%) were seen in 27 regions. Three networks were significant in common regions with key roles of PTK2, RPN2, EMR3, VAV1, NNAT, MUC16, MYC and YWHAZ genes. These data show that breast cancer arising by environmental carcinogens exemplifies genetic alterations differing from those observed in the non exposed ones. A number of genetic changes are shared in both tumor groups considered as crucial in breast cancer progression.
An extremely high prevalence of stomach cancer was observed in Mizoram (India), where the population consumes uncommon food. The relation of food habits and stomach cancer was examined in this study.
...A hospital-based case-control study was conducted during 2001-2004 to determine the risk factors among 329 patients with histologically confirmed stomach cancer and 658 matched controls. Food habits were determined by personal interview.
An elevated risk of stomach cancer was observed with frequent consumption of sa-um odds ratio (OR) 3.4 (sa-um is fermented pork fat, a traditional food) and with frequent consumption of smoked dried salted meat (OR 2.8) and fish (OR 2.5). Soda (alkali), used as a food additive, increased the risk of stomach cancer (OR 2.9). Helicobacter pylori infection was not found to be an independent risk factor for carcinogenesis of stomach cancer in this study. However, when H. pylori infection interacted with consumption of sa-um or smoked dried meat, it showed a significant association.
Peculiar food habits in Mizoram might be associated with the high prevalence of stomach cancer in Mizoram along with other factors. H. pylori infection might increase the risk of stomach cancer, or it may play a role as a promoter of stomach cancer in Mizoram.
Herpes simplex virus type-2 (HSV-2) is one of the most common sexually transmitted infections that facilitate human immunodeficiency virus (HIV) acquisition by over two fold or more. The development ...of HSV-2 control methods as a measure to control HIV epidemic in high HSV-2/HIV areas has become a priority. Two out of the six high HIV prevalent states of India are located in the Northeastern region of India. Due to lack of documented HSV-2 studies from this part of the country; there was a need for estimating the seroprevalence and risk factors of HSV-2 infection in this defined population.
Pregnant women (n = 1640) aged18 years and above attending antenatal clinics of tertiary referral hospitals in five Northeastern states of India were screened for type specific HSV-2 IgG antibodies. Blood samples were collected from all the participants after conducting interviews. Univariate and multivariate analyses were performed to identify the risk factors associated with HSV-2 seropositivity.
Overall seroprevalence of HSV-2 infection was 8.7% (142/1640; 95% CI 7.3-10.0) with a highest prevalence of 15.0% (46/307; 95% CI 11.0-19.0) in the state of Arunachal Pradesh. Higher seroprevalence was observed with increasing age (Adj. Odds Ratio AOR 1.9 for 22-25 years old, AOR 2.29 for > 29 years old). The risk factors associated with HSV-2 seropositives were multiple sex partners (AOR 2.5, p = 0.04), condom non-user's (AOR 4.7, p <0.001), early coitarchal age (age of first intercourse) 'less than 18 years' (AOR 9.6, p = 0.04), middle income group (AOR 2.1, p = 0.001) compared to low income group and low level of education (AOR 3.7, p = 0.02) compared to higher education. HSV-2 seropositivity was higher among Christians (12.6%) compared to Muslims (3.8%). The most frequent clinical symptoms among HSV-2 seropositives were excess vaginal discharge in last one year (53.5%, 76/142) and pelvic pain (26.1%, 37/142). While among subjects with genital ulcers, HSV-2 seroprevalence was 36.8% (7/19).
Overall seroprevalence of HSV-2 infection among pregnant women of Northeast India is relatively low. The generation of awareness among high risk groups may have played key role to limit the infection. The role of vaccination against HSV-2 in near future and elimination of HSV-2 viral shedding along with genital tract inflammation in high HIV/HSV-2 areas may be an option for initiating successful intervention strategies to reduce the transmission and acquisition of HIV infection in Northeast India.
Tobacco Use and Stomach Cancer in Mizoram, India Phukan, Rup Kumar; Zomawia, Eric; Narain, Kanwar ...
Cancer epidemiology, biomarkers & prevention,
08/2005, Letnik:
14, Številka:
8
Journal Article
Recenzirano
The incidence of stomach cancer in India is lower than that of any other country around the world. However, in Mizoram, one
of the north-eastern state of India, a very high age-adjusted incidence of ...stomach cancer is recorded. A hospital-based case-control
study was carried out to identify the influence of tobacco use on the risk of developing stomach cancer in Mizoram. Among
the cases, the risk of stomach cancer was significantly elevated among current smokers odds ratio (OR), 2.3; 95% confidence
interval (95% CI), 1.4-8.4 but not among ex-smokers. Higher risks were seen for meiziol (a local cigarette) smokers (OR, 2.2; 95% CI, 1.3-9.3). The increased risk was apparent among subjects who had smoked for
≥30 years. The increased risk was significant with 2-fold increase in risk among the subjects who smoked for ≥11 pack-years.
The risk increased with increasing cumulative dose of tobacco smoked (mg). Tuibur (tobacco smoke–infused water), used mainly in Mizoram, was seemed to increased the risk of stomach cancer among current users
in both univariate and multivariate models (OR, 2.1; 95% CI, 1.3-3.1). Tobacco chewer alone (OR, 2.6; 95% CI, 1.1-4.2) showed
significant risk. Tobacco use in any form smoking and smokeless ( tuibur and chewing) increased the risk of stomach cancer in Mizoram independently after adjusting for confounding variables.
Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, but is endemic in some ethnic groups. The association of NPC with the Epstein-Barr virus (EBV) is firmly established; ...however, the mechanism is still unclear. TLR9 is well known for its essential role in viral pathogen recognition and activation of innate immunity. Here, we report a set of TLR9 polymorphisms in the TIR-2 domain of the TLR9 protein collected from the EBV-infected NPC samples from northeast Indian populations sharing the aforesaid ethnicity. The occurrence of mutations is significantly high in these samples as we found a p value of <0.0001 at a significance level of 0.05. These might play an important role for the lack of function of TLR9 and thus for the higher occurrence of EBV-mediated NPC in such ethnic groups.
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•EBV-associated nasopharyngeal carcinoma (NPC) is endemic in Mongoloids•TLR9 is essential for virus recognition and immunity against cancers•Polymorphisms are common in TLR9 protein in EBV-infected Mongoloids with NPC•NPC susceptibility prediction by TLR9 mutation screening in people for prevention
Biological Sciences; Human Genetics; Cancer
A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV ...vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination.
In the randomised trial, unmarried girls aged 10–18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil Merck Sharp & Dohme, Whitehouse Station, NJ, USA; 0·5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702.
Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9·0 years (IQR 8·2–9·6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95·4% (95% CI 85·0–99·9) in the single-dose default cohort (2135 women assessed), 93·1% (77·3–99·8) in the two-dose cohort (1452 women assessed), and 93·3% (77·5–99·7) in three-dose recipients (1460 women assessed).
A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses.
Bill & Melinda Gates Foundation.
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