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    r> Materials and Methods
    Discussion The evidence available suggests that Vietnamese women have a low exposure to the known HPV co-factors, with low, constant prevalence of oral contraceptive usage, a low and declining smoking prevalence, and a declining fertility rate [55,56,57,58,71,72]. However, there is some evidence of a trend towards an earlier age of sexual PSB 1115 and a higher occurrence of pre-marital sex, which is probably related to changes in socio-economic status in Vietnam over the last two decades (1990s–2000s) [53,73]. These changes (in the absence of any further intervention) may result in an increase in the incidence of cervical cancer in the next 30 years in Vietnam, potentially countered to some degrees by socio-economic development [32]. Secondly, in both IARC-reported data (1990s and 2009–2012) and non-IARC reported data (2001–2008) a marked variation in cancer incidence was seen between northern cities/provinces (Hanoi, Hai Phong, Thai Nguyen) and southern cities/provinces (HCMC and Can Tho). Although there is a substantial reduction in the cervical cancer incidence in Ho Chi Minh City over the period 1995–2012, the most current cervical cancer rate (2009–2012) in HCMC still remain higher than the non-IARC-reported cancer rates of Hanoi and other northern provinces (2001–2008) (Appendix C, Table C1). This noticeable reduction of cervical cancer incidence in HCMC in the absence of both national cervical screening and HPV vaccination program could suggest that the peak of cervical cancer incidence rates reported for the period 1995–1998 in HCMC could be potentially associated with HPV exposure or exposure to the cofactors of HPV infection of that cohort in the past. Our review found that the differences in sexual behaviours between the north and south in older marriage cohorts (1960s–1970s) may explain the variation in cervical cancer incidence observed 20–30 years later (1990s). It is also possible that social conditions PSB 1115 during and after the Vietnam War in the 1960s–1970s may have differentially affected the patterns of sexual behaviour of the populations in these regions [74,75]. In the north, family planning services have been in place since 1963, and have mainly provided contraceptive services [76]. Additionally, during the Vietnam War many men were away from home, and as social norms required women to be strictly monogamous it is assumed that sexual activities were limited for many women in the north during that period. In contrast, the war mainly happened in the south where millions of local and foreigner soldiers were stationed, and thus sex services flourished in this area [77]. Therefore, evolutionary tree is possible that more women were then exposed to high-risk sexual behaviours, including having multiple sex partners, having sexually transmitted diseases, and having more children, given that a family planning program had not been implemented at that time in the south. As a result, cervical cancer incidence was often recorded at high rates in southern provinces [78]. Alman et al. reviewed fertility rates in Vietnam and found that in 1969–1974 the fertility rate in the south was 6.6 per women, compared to 5.7 children per women in the north [55]. After the reunification in 1975 the government expanded family planning services throughout the whole country [76]. However, the fertility rate still remained slightly higher in the south than in the north (5.1 vs. 4.7) in 1974–1979 [55]. The differences in sexual behaviours and reproductive health care systems between the north and south of Vietnam during and after the war may help explain the variation of cervical cancer in two regions in the 1990s. Fourthly, based on the data for cervical cancer incidence summarised in our review, some questions about the data not only for local cancer registries but also of the IARC-reported registries of Hanoi and HCM city should be considered. The low cervical cancer incidence rates (ASR: 3.5–5.5/100,000) reported by the non-certified local cancer registries suggests the possibility of under-registration. These incidence rates are lower than the reported incidence from a number of developed countries with well-established national cervical screening programs, such as the UK (ASR: 6.8/100.000) and New South Wales, Australia (ASR: 5.3/100.000) for 2003–2007 [79]. Additionally, the Hanoi cancer registries have not been continuously reported by IARC since they were first certified in the 1990s and most recently the HCMC registry was reported on for the second time using data for 2009–2012. Issues relating to lack of continuous certification/inclusion in IARC reporting could be related to meeting the criteria for data completeness and validity [80]. It was noted in the methodology section of IARC’s CI5, Volume VIII that only 75% and 85% of newly diagnosed cancer cases were histologically verified in these registries, and death certificates have not been used as a source of data [81]. Therefore, some under-registration or misclassification of cancer cases may have occurred in both the IARC-certified and non-IARC-certified cancer registries. The under-reporting of cancer incidence in the registries would probably result in underestimation of cancer incidence and mortality by GLOBOCAN 2012, which used data from non-IARC reported cancer registries – Hanoi (2007–2009) and HCMC (2006–2010) [70]. This underestimation issue might be similar to that identified in relation to the burden of cervical cancer in China as reported by Shi et al., 2012 [82].