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Benchmarking epidemiological characteristics of cervical cancer in advance of change in screening practice and commencement of vaccination

Benchmarking epidemiological characteristics of cervical cancer in advance of change in screening... Widespread cervical cytology screening has occurred in Australia, North America, Britain and other Western European countries since the 1960s, following studies that indicated a potential for public health benefit. Since then, South Australian age‐standardised cervical cancer mortality has reduced by more than 70%. Reductions in age‐standardised incidence of more than 40% also have been observed since cancer registration started in 1977. Elevated incidence rates have presented in Aboriginal and Torres Strait Islander women, the overseas born, especially women from Eastern Europe and Germany, and those residing in lower socio‐economic areas and certain country regions. While gains in survival from invasive disease have occurred in South Australia since the mid 1980s, these trends have not been statistically significant after adjusting for FIGO stage. It seems likely from available data that the mortality reduction observed in South Australia, and in Australia more generally, would largely be a result of early detection by screening of preinvasive and, to a lesser extent, invasive lesions. Epidemiological evidence indicates that biennial screening can prevent up to 90% of squamous cell carcinomas, but the evidence for benefit is less clear for glandular lesions (i.e. adenocarcinomas and adenosquamous lesions). Indeed, a greater prevention of squamous than glandular cancers may have contributed to the declining ratio of squamous to glandular cell types in Australia from about 4.0:1 to 3.5:1 between 1987 and 2002. The National Health and Medical Research Council endorsed revised guidelines for managing asymptomatic screen‐detected abnormalities in Australia in 2005, which focus more on the management of high‐grade abnormalities and of the more persistent of the low‐grade lesions. This is expected to reduce unnecessary investigation and treatment of transitory low‐grade abnormal‐ities. The guidelines are more cautious for glandular abnormalities, indicating that all these cytological abnormalities receive a colposcopic examination. Human Papilloma Virus (HPV) DNA testing has been recommended in these guidelines as a measure of effectiveness of treatment of high‐grade abnormalities. A national safety monitoring group has been established to check that the risk of invasive cancer is not affected adversely by the adoption of these guidelines. Other developments include increased use of liquid‐based cytology tests and the introduction of computerised cytology reading. Following trials of the effectiveness of the HPV vaccine in preventing pre‐invasive lesions, the Australian Therapeutic Drugs Administration has approved a HPV vaccine (Gardasil) for use by 9–26 year‐old females and 9–15 year‐old year old boys. This is likely to produce increased awareness in the community of cervical cancer as a sexually transmitted disease and of the potential for prevention through vaccination. The Australian public has received multiple messages in the media about the new cervical cancer vaccine, but less about advances in screening technology. There is the potential for confusion and a false expectation among some members that vaccination could have an immediate and far‐reaching preventive effect. The effect of such expectations on preventive behaviour and screening participation is yet to be determined. It seems appropriate, in the context of these developments and the recommended changes in clinical practice, to take stock of secular trends in cervical cancer incidence and mortality as a benchmark for evaluating future change. The present study was undertaken for this purpose, using data from the South Australian Cancer Registry. These data are similar to those collected by other Australian States and Territories and show broadly similar incidence and mortality trends. Because little emphasis has been placed on comparative analyses by histology type in South Australia, we describe secular trends in incidence and mortality, and of other epidemiological and survival differences, by histology type. Methods Data collection The South Australian Cancer Registry has received statutory notifications of invasive cancers since 1977. The registry is population based and covers all regions of the State. Its procedures have been described previously. Death data are collected through routine notifications, electronic searches of official State death records, the National Death Index at the Australian Institute of Health and Welfare, and from interstate cancer registries. Under‐ascertainment has been checked through active follow‐up and with deaths reported independently and found to be minimal, with little effect on calculated survival. This study included 1,920 invasive cervical cancers (ICD‐10: C53) diagnosed between 1977 and 2004, plus 644 deaths from cervical cancer occurring in this period. SNOMED II histology codes were used to classify these cancers as squamous cell carcinomas (8050/3–8082/3), glandular lesions (8140/3–8560/3), cancers of unknown histology (8000/3), and ‘other’ cancers (mostly comprising ill‐defined epithelial neoplasms and sarcomas). Socio‐demographic descriptors in this study included: age at diagnosis; region of residence, classified as 20 statistical subdivisions; country of birth (expressed using World Health Organization criteria); Indigenous status; and relative socio‐economic disadvantage, which was inferred from residential postcode characteristics using the SEIFA index and expressed as four ordinal categories. Statistical analyses A de‐identified file was extracted and analysed in‐house under provisions of the South Australian Health Commission Act using STATA 9.2 and SURV‐3 software. Mean annual incidence and mortality rates were calculated for four‐year periods from 1977 to 2004, directly standardising by five‐year age group (open‐ended category from 85 years) to the 2001 Australian reference population. Ninety‐five per cent confidence limits were approximated assuming a Poisson distribution, as in previous analyses. Rates were calculated for all ages combined and for females aged under 50 years, 50–69 years, and 70 years or more respectively, in order to visualise and describe secular trends. These age categories were chosen because secular trends for the five‐year age groups within them appeared similar. Differences in epidemiological characteristics of squamous and glandular cell lesions (96% of the total) were compared using multivariable logistic regression analysis. All socio‐demographic variables were entered as predictors of histology, with backwards elimination of those where the fit of the model did not reduce as a consequence ( p >0.05 ). Assumptions underlying the analysis, including an absence of collinearity, were found to be satisfied. Case survivals were calculated for the 1977–2003 diagnostic period, with a date of censoring of live cases of 31 December 2003. Deaths occurring in 2004 were excluded because the tracing of deaths occurring outside South Australia had not been completed. Kaplan‐Meier product‐limit estimates of disease‐specific survival were calculated, treating deaths from other causes as censored observations. This method was preferred to relative survival because life tables were not readily available for some subgroups. Analyses had shown very similar survival estimates in South Australia, irrespective of whether relative survival or disease‐specific survival was used. Respective relative and disease‐specific survivals also were found to be comparable for cervical cancers in this study, at 71% and 72% at five years from diagnosis, 68% and 69% at 10 years, and 66% and 68% at 15 years. Survival outcomes also were investigated using multivariable Cox proportional hazards regression, employing the same censoring criteria as for the Kaplan‐Meier analyses. All socio‐demographic variables, period of diagnosis, and histology type were entered into the analysis, with backwards elimination, as described for the logistic regression. Assumptions underlying the analysis, including proportionality and an absence of collinearity, were found to be satisfied. Results Incidence trends The annual incidence (95% confidence limits) per 100,000 for all histology types combined peaked at 13.93 (12.55–15.42) in 1985–88, but then reduced by 60.7% to 5.47 (4.70–6.34) in 2001–04 (see Table 1 and Figure 1 ). The peak in 1985–88 was influenced by an 80.0% increase in incidence between 1977–80 and 1985–88 among females under 50 years of age, which was followed by a progressive 58.2% decline in that age category by 2001–04 (see Table 2 ). By comparison, a progressive decline in incidence was evident in older females throughout the study period. 1 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,000 South Australian females by histology type and calendar year period. a Histology type (n=cases/dths) 1977–80 1981–84 1985–88 1989–92 1993–96 1997–2000 2001–04 Total (1977–2004) Incidence ( n=286 ) ( n=305 ) ( n=373 ) ( n=295 ) ( n=253 ) ( n=230 ) ( n=178 ) ( n=1,920 ) Squamous 9.50 10.19 11.13 7.89 5.88 5.10 3.99 7.40 ( n=1 ,466) (8.29–10.84) (8.96–11.53) (10.53–11.76) (6.90–8.98) (5.05–6.80) (4.35–5.95) (3.33–4.74) (7.02–7.79) Glandular 1.78 1.62 2.29 2.07 2.15 1.91 1.31 1.87 ( n=368 ) (1.29–2.40) (1.16–2.21) (1.76–2.94) (1.57–2.67) (1.66–2.74) (1.45–2.46) (0.94–1.77) (1.69–2.08) Other 0.73 0.35 0.43 0.18 0.20 0.21 0.12 0.29 ( n=61 ) (0.43–1.17) (0.16–0.66) (0.22–0.75) (0.07–0.39) (0.06–0.47) (0.08–0.43) (0.04–0.28) (0.22–0.37) Unknown 0.17 0.32 0.08 0.08 0.10 0.08 0.05 0.13 ( n=25 ) (0.05–0.44) (0.14–0.63) (0.01–0.29) (0.02–0.23) (0.02–0.29) (0.01–0.23) (0.01–0.18) (0.08–0.19) Total 12.18 12.48 13.9 10.22 8.33 7.30 5.47 9.69 ( n=1 ,920) (10.81–13.68) (11.12–13.96) (12.55–15.42) (9.09–11.46) (7.34–9.42) (6.39–8.31) (4.70–6.34) (9.26–10.13) Mortality ( n=121 ) ( n=105 ) ( n=94 ) ( n=109 ) ( n=78 ) ( n=63 ) ( n=74 ) ( n=644 ) Squamous 3.58 3.18 2.66 2.65 1.71 1.20 1.52 2.23 ( n=460 ) (2.86–4.43) (2.51–3.96) (2.09–3.35) (2.09–3.30) (1.29–2.23) (0.86–1.63) (1.13–2.00) (2.03–2.44) Glandular 0.46 0.70 0.67 0.67 0.58 0.44 0.47 0.57 ( n=118 ) (0.24–0.81) (0.41–1.10) (0.40–1.06) (0.41–1.03) (0.35–0.92) (0.25–0.72) (0.28–0.76) (0.47–0.68) Other 0.72 0.11 0.14 0.23 0.12 0.09 0.05 0.20 ( n=43 ) (0.42–1.15) (0.02–0.32) (0.04–0.36) (0.09–0.47) (0.03–0.31) (0.02–0.26) (0.02–0.12) (0.14–0.27) Unknown 0.32 0.22 0.00 0.10 0.03 0.09 0.03 0.10 ( n=23 ) (0.13–0.66) (0.08–0.48) (0.00–0.00) (0.02–0.29) (0.00–0.17) (0.02–0.23) (0.00–0.17) (0.06–0.15) Total 5.08 4.21 3.47 3.65 2.44 1.82 2.07 3.10 ( n=644 ) (4.22–6.07) (3.45–5.10) (2.81–4.25) (2.99–4.40) (1.93–3.05) (1.40–2.33) (1.62–2.59) (2.87–3.35) Note: (a) Data source: South Australian Cancer Registry. 1 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,00 South Australian females by calendar year period.* 2 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,000 South Australian females by age and calendar year period; all histological types combined. a Age (yrs) (n=cases/dths) 1977–80 1981–84 1985–88 1989–92 1993–96 1997–2000 2001–04 Total (1977–2004) Incidence ( n=286 ) ( n=305 ) ( n=373 ) ( n=295 ) ( n=253 ) ( n=230 ) ( n=178 ) ( n=1,920 ) Under 50 6.21 8.22 11.18 8.90 6.27 5.67 4.67 7.19 ( n=965 ) (5.03–7.58) (6.89–9.74) (9.70–12.82) (7.65–10.30) (5.25–7.44) (4.70–6.78) (3.79–5.69) (6.74–7.66) 50–69 25.95 22.45 19.53 13.39 12.00 10.70 6.68 15.31 ( n=607 ) (21.73–30.75) (18.55–26.93) (16.01–23.60) (10.55–16.76) (9.30–15.24) (8.24–13.66) (4.85–8.97) (14.12–16.58) 70+ 29.18 24.32 23.32 13.57 16.44 12.76 9.06 17.01 ( n=348 ) (22.10–37.81) (18.32–31.66) (17.84–29.96) (9.65–18.55) (12.35–21.45) (9.34–17.02) (6.34–12.54) (15.27–18.89) Mortality ( n=121 ) ( n=105 ) ( n=94 ) ( n=109 ) ( n=78 ) ( n=63 ) ( n=74 ) ( n=644 ) Under 50 0.99 1.24 1.19 1.88 0.86 0.56 0.92 1.08 ( n=141 ) (0.55–1.63) (0.75–1.94) (0.73–1.83) (1.32–2.58) (0.51–1.36) (0.29–0.97) (0.56–1.41) (0.91–1.27) 50–69 11.16 7.91 7.62 5.14 4.07 3.70 4.27 6.11 ( n=248 ) (8.49–14.39) (5.70–10.69) (5.49–10.30) (3.49–7.30) (2.58–6.11) (2.34–5.55) (2.84–6.17) (5.37–6.92) 70+ 24.05 19.51 12.45 14.28 11.28 7.70 6.32 12.42 ( n=255 ) (17.67–31.98) (14.18–26.19) (8.51–17.58) (10.24–19.37) (7.94–15.55) (5.12–11.13) (4.13–9.26) (10.94–14.04) Note: (a) Data source: South Australian Cancer Registry. Squamous cell carcinomas accounted for 76.4% of all lesions and showed the same secular trends as all histology types combined with a peak annual incidence in 1985–88, which was followed by a 64.2% reduction to 2001–04 (see Table 1 ). For females under 50 years of age, a 72.6% increase applied between 1977–80 and 1985–88, followed by a 61.8% decline, whereas progressive declines were evident throughout the study period in the older age groups (see Table 3 ). 3 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,000 South Australian females by age and calendar year period; squamous cell carcinomas. a Age (yrs) (n=cases/dths) 1977–80 1981–84 1985–88 1989–92 1993–96 1997–2000 2001–04 Total (1977–2004) Incidence ( n=222 ) ( n=248 ) ( n=297 ) ( n=229 ) ( n=179 ) ( n=161 ) ( n=130 ) ( n=1,466 ) Under 50 5.07 6.62 8.75 7.10 4.51 3.97 3.34 5.50 ( n=737 ) (4.01–6.33) (5.42–7.99) (7.45–10.22) (5.99–8.36) (3.65–5.51) (3.17–4.92) (2.60–4.21) (5.11–5.91) 50–69 19.08 18.60 15.71 9.56 8.19 7.32 5.16 11.57 ( n=459 ) (15.49–23.26) (15.06–22.71) (12.56–19.40) (7.20–12.45) (6.00–10.93) (5.32–9.83) (3.57–7.21) (10.54–12.68) 70+ 23.52 19.97 19.81 10.37 11.55 9.14 6.53 13.21 ( n=270 ) (17.21–31.37) (14.37–26.36) (14.80–25.98) (7.00–14.81) (8.17–15.85) (6.29–12.83) (4.26–9.56) (11.68–14.88) Mortality ( n=85 ) ( n=78 ) ( n=73 ) ( n=78 ) ( n=55 ) ( n=41 ) ( n=50 ) ( n=460 ) Under 50 0.74 1.09 0.82 1.48 0.77 0.51 0.65 0.85 ( n=111 ) (0.37–1.32) (0.62–1.77) (0.45–1.37) (0.99–2.13) (0.44–1.24) (0.25–0.90) (0.35–1.09) (0.70–1.03) 50–69 8.20 5.06 5.93 3.26 2.13 2.23 3.47 4.14 ( n=167 ) (5.93–11.05) (3.33–7.36) (4.08–8.33) (1.96–5.10) (1.10–3.71) (1.22–3.74) (2.09–5.42) (3.56–4.78) 70+ 15.94 15.46 10.07 10.42 8.22 4.41 4.12 8.87 ( n=182 ) (10.83–22.62) (10.77–21.50) (6.58–14.76) (7.03–14.88) (5.41–11.96) (2.52–7.17) (2.40–6.59) (7.63–10.26) Note: (a) Data source: South Australian Cancer Registry. Glandular cancers (19.2% of the total) showed less pronounced secular trends than squamous lesions that were not statistically significant with the numbers available for analysis (see Table 1 ). Nonetheless, the peak annual rate per 100,000 was 2.29 (1.76–2.94) in 1985–98 for all ages combined due to a peak for females under 50 years, and the lowest rate was 1.31 (0.94–1.77) in 2001–04. Although based on small numbers, a downward trend was suggested for ‘other’ and unknown histology types (see Table 1 ). Due to a steeper downward trend in incidence of squamous than glandular lesions, the ratio of age‐standardised rates for these lesions declined for all ages combined from 5.4:1 in 1977–88 to 2.8:1 in 1993–2004, with an intermediary ratio of 3.8:1 in 1989–92. Similar secular trends applied for each age category, although in general the ratio was lowest at 3.7:1 in females under 50 years and highest at 5.6:1 in those aged 70 years or more. Mortality trends The annual mortality rate per 100,000 for all histology types combined decreased by 59.3% from 5.08 (4.22–6.07) in 1977–80 to 2.07 (1.62–2.59) in 2001–04 (see Table 1 and Figure 1 ). The decline was more pronounced at 73.7% for females aged 70 years or more than the 61.7% reduction recorded in 50–69 year olds, whereas there was not clear evidence of a reduction in younger women (see Table 2 ). Squamous cell cancers, which accounted for 71.4% of cervical cancer deaths, presented similar secular changes to the total, with a 57.5% reduction in age‐standardised mortality occurring between 1977–80 and 2001–04 for all ages combined (see Table 1 ). The largest decline was 74.2% for females aged 70 years or more, which compared with a corresponding 57.7% reduction for 50–69 year‐olds, and less evidence of a trend among younger women (see Table 3 ). Glandular lesions, which accounted for 18.3% of all deaths, did not show a progressive decline in annual mortality, whereas downward trends in deaths from ‘other’ and unknown histology types were suggested, despite small numbers (see Table 1 ). As for incidence data, the ratio of squamous to glandular cell standardised mortality reduced over time, from 5.1:1 in 1977–88 to 3.0:1 in 1993–2004, with an intermediary ratio of 4.0:1 in 1989–92. Again, similar secular trends applied for each age category. Epidemiological differences Multivariable logistic regression indicated that predictors of glandular as opposed to squamous cell cancers included an age at diagnosis of less than 70 years, residing in a higher socio‐economic area, and having a more recently diagnosed cancer (at least during the 1977–2000 period) (see Table 4 ). Age categories under 70 years were combined because including them separately did not increase model fit. Their predictive effects by histology type were observed during model development to be very similar. Meanwhile, the relative ratios (95% confidence limits) of glandular to squamous lesions were low at 0.43 (0.20–0.91) for females born in Southern Europe and 0.12 (0.02–0.86) for Aboriginal and Torres Strait Islander women. Place of residence was not predictive of histology type ( p >0.10 ), irrespective of whether it was expressed as statistical subdivision or more broadly as metropolitan or non‐metropolitan. 4 Relative ratios (95% confidence limits) of glandular cancers (adeno/adenosquamous cell carcinomas) to squamous cell carcinomas, by socio‐demographic characteristic and diagnostic period: invasive cervical cancers, South Australia, 1977–2004. a Multiple logistic regression Characteristic (n=cases) Relative ratio Age at diagnosis (years) Under 70 (reference) ( n=1 ,334) 1.00 70–79 ( n=212 ) 0.65 (0.43–0.96) 80+ ( n=104 ) 0.53 (0.30–0.94) Socio‐economic status Other (reference) ( n=1 ,295) 1.00 High ( n=355 ) 1.46 (1.10–1.93) Country of birth Other (reference) (n=1,572) 1.00 Southern Europe ( n=78 ) 0.43 (0.20–0.91) Race Other (reference) (n=1,620) 1.00 Aboriginal/Torres Strait Islander ( n=30 ) 0.12 (0.02–0.86) Diagnostic period 1977–88 (reference) ( n=874 ) 1.00 1989–92 ( n=244 ) 1.54 (1.08–2.20) 1993–96 ( n=213 ) 2.02 (1.41–2.89) 1997–2000 ( n=183 ) 2.22 (1.53–3.23) 2001–04 ( n=136 ) 1.61 (1.03–2.51) Note: (a) Excluding 10% of cases with missing information on race or country of birth. Survivals Survivals were 72.4% at five years from diagnosis, 69.4% at 10 years, 68.1% at 15 years, and 67.0% at 20 years. The older the age at diagnosis, the lower was the survival ( p <0.001 ), with five‐year figures reducing from 90.3% for those under 30 years to 31.8% for females aged 80 years or more. A survival difference also was evident by histology type ( p <0.001 ), with the highest five‐year survival of 74.4% applying to squamous cell cancers as compared with a corresponding 70.1% for glandular cancers, 45.5% for other histology types, and 59.1% for those of unknown type. Diagnostic period was another predictor of survival ( p <0.001 ), with cases diagnosed in 1985–2003 having a higher five‐year survival of 75.4% as compared with figures of 67.1% for 1981–84 and 65.4% for 1977–80. Multivariable proportions hazards regression confirmed that the relative risk of case fatality increased with older age at diagnosis and was higher for glandular and (more so) ‘other’ histology types than for squamous cell lesions (see Table 5 ). Aboriginal and Torres Strait Islander women had an elevated relative risk (95% confidence limits) of 2.14 (1.17–3.92) when compared with other women. A lower relative risk was evident for cases diagnosed more recently, at 0.74 (0.62–0.89) for 1985–2003 compared with 1977–84. Further analyses by calendar year within 1985–2003 did not reveal a difference in outcome ( p =0.35 ). Place of residence was not predictive of outcome ( p >0.10 ), irrespective of the classification used. 5 Relative risks (95% confidence limits) of case fatality from cervical cancer in South Australia by socio‐demographic characteristic, histology type and diagnostic period, 1977–2003. a Characteristic (n=cases) Relative risk Age at diagnosis (years) Under 40 (reference) ( n=539 ) 1.00 40–49 ( n=391 ) 2.04 (1.48–2.82) 50–59 ( n=266 ) 2.88 (2.08–3.99) 60–69 ( n=320 ) 4.24 (3.15–5.72) 70–79 ( n=217 ) 5.45 (3.98–7.47) 80+ ( n=117 ) 12.62 (8.98–17.72) Histology type Squamous cell carc. (reference) (n=1,436) 1.00 Glandular cell ( n=354 ) 1.34 (1.08–1.66) Other ( n=60 ) 2.54 (1.78–3.64) Race Other (reference) (n=1,820) 1.00 Aboriginal/Torres Strait Islander ( n=30 ) 2.14 (1.17–3.92) Diagnostic year 1977–84 (reference) ( n=579 ) 1.00 1985–2003 (n=1,271) 0.74 (0.62–0.89) Note: (a) Multivariable Cox proportional hazards regression (see text): Date of censoring of live cases – 31 December 2003. Discussion The reduction of 55% in incidence and 59% in mortality between 1977–80 and 2001–04, as indicated by the age‐standardised rates, is consistent with trends for Australia overall and for several economically developed countries. It seems likely that the more detailed trends reported now by histology type apply to Australia as a whole. The 80% increase in incidence between 1977–80 and 1985–88 in females less than 50 years of age is also consistent with trends reported in younger age groups in other Australian, New Zealand, North American, British and Eastern European populations. It has been suggested that this increase may reflect changes in sexual behaviour and HPV transmission, although an effect from changes in screening coverage or data ascertainment by the cancer registry cannot be discounted. By comparison, there was no sign of an increase in older age groups in this study. Irrespective of age, incidence rates declined between 1985–88 and 2001–04. Investigation of factors responsible for incidence declines would require data on age at first intercourse, numbers of sexual partners, other risk factors, and screening practices not routinely collected by cancer registries. Of necessity, our analyses have been restricted to the limited range of data items available through this source. The trends in incidence for all histology types combined were reflected in the data for squamous cell carcinomas. Glandular lesions were smaller in number, which complicated assessments of secular trends, especially by age. Nonetheless, although the difference in rates was not statistically significant ( p >0.05 ), the peak for glandular lesions was in 1985–88 and the lowest incidence in 2001–04, as for squamous cell cancers. National data also point to a relatively low incidence of glandular lesions in recent years, which may reflect an emerging benefit from screening. Although based on small numbers, a downward trend in incidence and mortality was suggested for ‘other’ and unknown histology types. While this may reflect true declines, it is also possible that improvements in coding have played a part. Due to larger reductions in incidence for squamous cell than glandular lesions, the ratio of age‐standardised incidence rates for the former to latter reduced from 5.4:1 in 1977–88 to 2.8:1 in 1993–2004, and a similar trend applied for mortality data. It is evident that glandular lesions have become proportionally more common. In particular, these lesions are proportionally more common in patients from the upper socio‐economic residential areas. By comparison, glandular lesions are less commonly encountered in patients over 70 years of age, Aboriginal or Torres Strait Islanders, and those patients born in Southern Europe. Opportunities to prevent glandular cancers through pre‐invasive detection may be more limited, reducing the proportional contribution of these cancers to total numbers of cervical cancers in less frequently screened sections of the community, such as women over 70 years of age, Aboriginal and Torres Strait Islanders, residents of lower socio‐economic areas, and potentially women born in Southern Europe. Hopefully HPV vaccination will have an important role in the prevention of glandular as well as squamous cancers. Approximately two‐thirds of women with cervical cancer survive their disease 20 years or more after diagnosis. Survivals are higher for younger women, those with squamous cell compared with other cancers, non‐Indigenous than Indigenous women, and women diagnosed in the 1985–2003 period compared with earlier years. Again, the poorer outcomes for glandular lesions highlight the importance of preventing them through vaccination or finding their pre‐invasive precursors through screening. Indigenous women have a death rate from cervical cancer about four to five times that of the non‐Indigenous population in Australia, which reflects their high incidence rates and low cancer case survivals. Opportunities to reduce this inequality through more active targeting of cervical cytology screening and, in the longer term, through vaccination need to be pursued actively. Acknowledgements Staff members of the South Australian Cancer Registry are thanked for the care taken over so many years in the collection of data used in this study. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Australian and New Zealand Journal of Public Health Wiley

Benchmarking epidemiological characteristics of cervical cancer in advance of change in screening practice and commencement of vaccination

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Publisher
Wiley
Copyright
Copyright © 2007 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1326-0200
eISSN
1753-6405
DOI
10.1111/j.1753-6405.2007.00033.x
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See Article on Publisher Site

Abstract

Widespread cervical cytology screening has occurred in Australia, North America, Britain and other Western European countries since the 1960s, following studies that indicated a potential for public health benefit. Since then, South Australian age‐standardised cervical cancer mortality has reduced by more than 70%. Reductions in age‐standardised incidence of more than 40% also have been observed since cancer registration started in 1977. Elevated incidence rates have presented in Aboriginal and Torres Strait Islander women, the overseas born, especially women from Eastern Europe and Germany, and those residing in lower socio‐economic areas and certain country regions. While gains in survival from invasive disease have occurred in South Australia since the mid 1980s, these trends have not been statistically significant after adjusting for FIGO stage. It seems likely from available data that the mortality reduction observed in South Australia, and in Australia more generally, would largely be a result of early detection by screening of preinvasive and, to a lesser extent, invasive lesions. Epidemiological evidence indicates that biennial screening can prevent up to 90% of squamous cell carcinomas, but the evidence for benefit is less clear for glandular lesions (i.e. adenocarcinomas and adenosquamous lesions). Indeed, a greater prevention of squamous than glandular cancers may have contributed to the declining ratio of squamous to glandular cell types in Australia from about 4.0:1 to 3.5:1 between 1987 and 2002. The National Health and Medical Research Council endorsed revised guidelines for managing asymptomatic screen‐detected abnormalities in Australia in 2005, which focus more on the management of high‐grade abnormalities and of the more persistent of the low‐grade lesions. This is expected to reduce unnecessary investigation and treatment of transitory low‐grade abnormal‐ities. The guidelines are more cautious for glandular abnormalities, indicating that all these cytological abnormalities receive a colposcopic examination. Human Papilloma Virus (HPV) DNA testing has been recommended in these guidelines as a measure of effectiveness of treatment of high‐grade abnormalities. A national safety monitoring group has been established to check that the risk of invasive cancer is not affected adversely by the adoption of these guidelines. Other developments include increased use of liquid‐based cytology tests and the introduction of computerised cytology reading. Following trials of the effectiveness of the HPV vaccine in preventing pre‐invasive lesions, the Australian Therapeutic Drugs Administration has approved a HPV vaccine (Gardasil) for use by 9–26 year‐old females and 9–15 year‐old year old boys. This is likely to produce increased awareness in the community of cervical cancer as a sexually transmitted disease and of the potential for prevention through vaccination. The Australian public has received multiple messages in the media about the new cervical cancer vaccine, but less about advances in screening technology. There is the potential for confusion and a false expectation among some members that vaccination could have an immediate and far‐reaching preventive effect. The effect of such expectations on preventive behaviour and screening participation is yet to be determined. It seems appropriate, in the context of these developments and the recommended changes in clinical practice, to take stock of secular trends in cervical cancer incidence and mortality as a benchmark for evaluating future change. The present study was undertaken for this purpose, using data from the South Australian Cancer Registry. These data are similar to those collected by other Australian States and Territories and show broadly similar incidence and mortality trends. Because little emphasis has been placed on comparative analyses by histology type in South Australia, we describe secular trends in incidence and mortality, and of other epidemiological and survival differences, by histology type. Methods Data collection The South Australian Cancer Registry has received statutory notifications of invasive cancers since 1977. The registry is population based and covers all regions of the State. Its procedures have been described previously. Death data are collected through routine notifications, electronic searches of official State death records, the National Death Index at the Australian Institute of Health and Welfare, and from interstate cancer registries. Under‐ascertainment has been checked through active follow‐up and with deaths reported independently and found to be minimal, with little effect on calculated survival. This study included 1,920 invasive cervical cancers (ICD‐10: C53) diagnosed between 1977 and 2004, plus 644 deaths from cervical cancer occurring in this period. SNOMED II histology codes were used to classify these cancers as squamous cell carcinomas (8050/3–8082/3), glandular lesions (8140/3–8560/3), cancers of unknown histology (8000/3), and ‘other’ cancers (mostly comprising ill‐defined epithelial neoplasms and sarcomas). Socio‐demographic descriptors in this study included: age at diagnosis; region of residence, classified as 20 statistical subdivisions; country of birth (expressed using World Health Organization criteria); Indigenous status; and relative socio‐economic disadvantage, which was inferred from residential postcode characteristics using the SEIFA index and expressed as four ordinal categories. Statistical analyses A de‐identified file was extracted and analysed in‐house under provisions of the South Australian Health Commission Act using STATA 9.2 and SURV‐3 software. Mean annual incidence and mortality rates were calculated for four‐year periods from 1977 to 2004, directly standardising by five‐year age group (open‐ended category from 85 years) to the 2001 Australian reference population. Ninety‐five per cent confidence limits were approximated assuming a Poisson distribution, as in previous analyses. Rates were calculated for all ages combined and for females aged under 50 years, 50–69 years, and 70 years or more respectively, in order to visualise and describe secular trends. These age categories were chosen because secular trends for the five‐year age groups within them appeared similar. Differences in epidemiological characteristics of squamous and glandular cell lesions (96% of the total) were compared using multivariable logistic regression analysis. All socio‐demographic variables were entered as predictors of histology, with backwards elimination of those where the fit of the model did not reduce as a consequence ( p >0.05 ). Assumptions underlying the analysis, including an absence of collinearity, were found to be satisfied. Case survivals were calculated for the 1977–2003 diagnostic period, with a date of censoring of live cases of 31 December 2003. Deaths occurring in 2004 were excluded because the tracing of deaths occurring outside South Australia had not been completed. Kaplan‐Meier product‐limit estimates of disease‐specific survival were calculated, treating deaths from other causes as censored observations. This method was preferred to relative survival because life tables were not readily available for some subgroups. Analyses had shown very similar survival estimates in South Australia, irrespective of whether relative survival or disease‐specific survival was used. Respective relative and disease‐specific survivals also were found to be comparable for cervical cancers in this study, at 71% and 72% at five years from diagnosis, 68% and 69% at 10 years, and 66% and 68% at 15 years. Survival outcomes also were investigated using multivariable Cox proportional hazards regression, employing the same censoring criteria as for the Kaplan‐Meier analyses. All socio‐demographic variables, period of diagnosis, and histology type were entered into the analysis, with backwards elimination, as described for the logistic regression. Assumptions underlying the analysis, including proportionality and an absence of collinearity, were found to be satisfied. Results Incidence trends The annual incidence (95% confidence limits) per 100,000 for all histology types combined peaked at 13.93 (12.55–15.42) in 1985–88, but then reduced by 60.7% to 5.47 (4.70–6.34) in 2001–04 (see Table 1 and Figure 1 ). The peak in 1985–88 was influenced by an 80.0% increase in incidence between 1977–80 and 1985–88 among females under 50 years of age, which was followed by a progressive 58.2% decline in that age category by 2001–04 (see Table 2 ). By comparison, a progressive decline in incidence was evident in older females throughout the study period. 1 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,000 South Australian females by histology type and calendar year period. a Histology type (n=cases/dths) 1977–80 1981–84 1985–88 1989–92 1993–96 1997–2000 2001–04 Total (1977–2004) Incidence ( n=286 ) ( n=305 ) ( n=373 ) ( n=295 ) ( n=253 ) ( n=230 ) ( n=178 ) ( n=1,920 ) Squamous 9.50 10.19 11.13 7.89 5.88 5.10 3.99 7.40 ( n=1 ,466) (8.29–10.84) (8.96–11.53) (10.53–11.76) (6.90–8.98) (5.05–6.80) (4.35–5.95) (3.33–4.74) (7.02–7.79) Glandular 1.78 1.62 2.29 2.07 2.15 1.91 1.31 1.87 ( n=368 ) (1.29–2.40) (1.16–2.21) (1.76–2.94) (1.57–2.67) (1.66–2.74) (1.45–2.46) (0.94–1.77) (1.69–2.08) Other 0.73 0.35 0.43 0.18 0.20 0.21 0.12 0.29 ( n=61 ) (0.43–1.17) (0.16–0.66) (0.22–0.75) (0.07–0.39) (0.06–0.47) (0.08–0.43) (0.04–0.28) (0.22–0.37) Unknown 0.17 0.32 0.08 0.08 0.10 0.08 0.05 0.13 ( n=25 ) (0.05–0.44) (0.14–0.63) (0.01–0.29) (0.02–0.23) (0.02–0.29) (0.01–0.23) (0.01–0.18) (0.08–0.19) Total 12.18 12.48 13.9 10.22 8.33 7.30 5.47 9.69 ( n=1 ,920) (10.81–13.68) (11.12–13.96) (12.55–15.42) (9.09–11.46) (7.34–9.42) (6.39–8.31) (4.70–6.34) (9.26–10.13) Mortality ( n=121 ) ( n=105 ) ( n=94 ) ( n=109 ) ( n=78 ) ( n=63 ) ( n=74 ) ( n=644 ) Squamous 3.58 3.18 2.66 2.65 1.71 1.20 1.52 2.23 ( n=460 ) (2.86–4.43) (2.51–3.96) (2.09–3.35) (2.09–3.30) (1.29–2.23) (0.86–1.63) (1.13–2.00) (2.03–2.44) Glandular 0.46 0.70 0.67 0.67 0.58 0.44 0.47 0.57 ( n=118 ) (0.24–0.81) (0.41–1.10) (0.40–1.06) (0.41–1.03) (0.35–0.92) (0.25–0.72) (0.28–0.76) (0.47–0.68) Other 0.72 0.11 0.14 0.23 0.12 0.09 0.05 0.20 ( n=43 ) (0.42–1.15) (0.02–0.32) (0.04–0.36) (0.09–0.47) (0.03–0.31) (0.02–0.26) (0.02–0.12) (0.14–0.27) Unknown 0.32 0.22 0.00 0.10 0.03 0.09 0.03 0.10 ( n=23 ) (0.13–0.66) (0.08–0.48) (0.00–0.00) (0.02–0.29) (0.00–0.17) (0.02–0.23) (0.00–0.17) (0.06–0.15) Total 5.08 4.21 3.47 3.65 2.44 1.82 2.07 3.10 ( n=644 ) (4.22–6.07) (3.45–5.10) (2.81–4.25) (2.99–4.40) (1.93–3.05) (1.40–2.33) (1.62–2.59) (2.87–3.35) Note: (a) Data source: South Australian Cancer Registry. 1 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,00 South Australian females by calendar year period.* 2 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,000 South Australian females by age and calendar year period; all histological types combined. a Age (yrs) (n=cases/dths) 1977–80 1981–84 1985–88 1989–92 1993–96 1997–2000 2001–04 Total (1977–2004) Incidence ( n=286 ) ( n=305 ) ( n=373 ) ( n=295 ) ( n=253 ) ( n=230 ) ( n=178 ) ( n=1,920 ) Under 50 6.21 8.22 11.18 8.90 6.27 5.67 4.67 7.19 ( n=965 ) (5.03–7.58) (6.89–9.74) (9.70–12.82) (7.65–10.30) (5.25–7.44) (4.70–6.78) (3.79–5.69) (6.74–7.66) 50–69 25.95 22.45 19.53 13.39 12.00 10.70 6.68 15.31 ( n=607 ) (21.73–30.75) (18.55–26.93) (16.01–23.60) (10.55–16.76) (9.30–15.24) (8.24–13.66) (4.85–8.97) (14.12–16.58) 70+ 29.18 24.32 23.32 13.57 16.44 12.76 9.06 17.01 ( n=348 ) (22.10–37.81) (18.32–31.66) (17.84–29.96) (9.65–18.55) (12.35–21.45) (9.34–17.02) (6.34–12.54) (15.27–18.89) Mortality ( n=121 ) ( n=105 ) ( n=94 ) ( n=109 ) ( n=78 ) ( n=63 ) ( n=74 ) ( n=644 ) Under 50 0.99 1.24 1.19 1.88 0.86 0.56 0.92 1.08 ( n=141 ) (0.55–1.63) (0.75–1.94) (0.73–1.83) (1.32–2.58) (0.51–1.36) (0.29–0.97) (0.56–1.41) (0.91–1.27) 50–69 11.16 7.91 7.62 5.14 4.07 3.70 4.27 6.11 ( n=248 ) (8.49–14.39) (5.70–10.69) (5.49–10.30) (3.49–7.30) (2.58–6.11) (2.34–5.55) (2.84–6.17) (5.37–6.92) 70+ 24.05 19.51 12.45 14.28 11.28 7.70 6.32 12.42 ( n=255 ) (17.67–31.98) (14.18–26.19) (8.51–17.58) (10.24–19.37) (7.94–15.55) (5.12–11.13) (4.13–9.26) (10.94–14.04) Note: (a) Data source: South Australian Cancer Registry. Squamous cell carcinomas accounted for 76.4% of all lesions and showed the same secular trends as all histology types combined with a peak annual incidence in 1985–88, which was followed by a 64.2% reduction to 2001–04 (see Table 1 ). For females under 50 years of age, a 72.6% increase applied between 1977–80 and 1985–88, followed by a 61.8% decline, whereas progressive declines were evident throughout the study period in the older age groups (see Table 3 ). 3 Annual age‐standardised (Australia, 2001) incidence and mortality rates (95% confidence limits) for cervical cancer per 100,000 South Australian females by age and calendar year period; squamous cell carcinomas. a Age (yrs) (n=cases/dths) 1977–80 1981–84 1985–88 1989–92 1993–96 1997–2000 2001–04 Total (1977–2004) Incidence ( n=222 ) ( n=248 ) ( n=297 ) ( n=229 ) ( n=179 ) ( n=161 ) ( n=130 ) ( n=1,466 ) Under 50 5.07 6.62 8.75 7.10 4.51 3.97 3.34 5.50 ( n=737 ) (4.01–6.33) (5.42–7.99) (7.45–10.22) (5.99–8.36) (3.65–5.51) (3.17–4.92) (2.60–4.21) (5.11–5.91) 50–69 19.08 18.60 15.71 9.56 8.19 7.32 5.16 11.57 ( n=459 ) (15.49–23.26) (15.06–22.71) (12.56–19.40) (7.20–12.45) (6.00–10.93) (5.32–9.83) (3.57–7.21) (10.54–12.68) 70+ 23.52 19.97 19.81 10.37 11.55 9.14 6.53 13.21 ( n=270 ) (17.21–31.37) (14.37–26.36) (14.80–25.98) (7.00–14.81) (8.17–15.85) (6.29–12.83) (4.26–9.56) (11.68–14.88) Mortality ( n=85 ) ( n=78 ) ( n=73 ) ( n=78 ) ( n=55 ) ( n=41 ) ( n=50 ) ( n=460 ) Under 50 0.74 1.09 0.82 1.48 0.77 0.51 0.65 0.85 ( n=111 ) (0.37–1.32) (0.62–1.77) (0.45–1.37) (0.99–2.13) (0.44–1.24) (0.25–0.90) (0.35–1.09) (0.70–1.03) 50–69 8.20 5.06 5.93 3.26 2.13 2.23 3.47 4.14 ( n=167 ) (5.93–11.05) (3.33–7.36) (4.08–8.33) (1.96–5.10) (1.10–3.71) (1.22–3.74) (2.09–5.42) (3.56–4.78) 70+ 15.94 15.46 10.07 10.42 8.22 4.41 4.12 8.87 ( n=182 ) (10.83–22.62) (10.77–21.50) (6.58–14.76) (7.03–14.88) (5.41–11.96) (2.52–7.17) (2.40–6.59) (7.63–10.26) Note: (a) Data source: South Australian Cancer Registry. Glandular cancers (19.2% of the total) showed less pronounced secular trends than squamous lesions that were not statistically significant with the numbers available for analysis (see Table 1 ). Nonetheless, the peak annual rate per 100,000 was 2.29 (1.76–2.94) in 1985–98 for all ages combined due to a peak for females under 50 years, and the lowest rate was 1.31 (0.94–1.77) in 2001–04. Although based on small numbers, a downward trend was suggested for ‘other’ and unknown histology types (see Table 1 ). Due to a steeper downward trend in incidence of squamous than glandular lesions, the ratio of age‐standardised rates for these lesions declined for all ages combined from 5.4:1 in 1977–88 to 2.8:1 in 1993–2004, with an intermediary ratio of 3.8:1 in 1989–92. Similar secular trends applied for each age category, although in general the ratio was lowest at 3.7:1 in females under 50 years and highest at 5.6:1 in those aged 70 years or more. Mortality trends The annual mortality rate per 100,000 for all histology types combined decreased by 59.3% from 5.08 (4.22–6.07) in 1977–80 to 2.07 (1.62–2.59) in 2001–04 (see Table 1 and Figure 1 ). The decline was more pronounced at 73.7% for females aged 70 years or more than the 61.7% reduction recorded in 50–69 year olds, whereas there was not clear evidence of a reduction in younger women (see Table 2 ). Squamous cell cancers, which accounted for 71.4% of cervical cancer deaths, presented similar secular changes to the total, with a 57.5% reduction in age‐standardised mortality occurring between 1977–80 and 2001–04 for all ages combined (see Table 1 ). The largest decline was 74.2% for females aged 70 years or more, which compared with a corresponding 57.7% reduction for 50–69 year‐olds, and less evidence of a trend among younger women (see Table 3 ). Glandular lesions, which accounted for 18.3% of all deaths, did not show a progressive decline in annual mortality, whereas downward trends in deaths from ‘other’ and unknown histology types were suggested, despite small numbers (see Table 1 ). As for incidence data, the ratio of squamous to glandular cell standardised mortality reduced over time, from 5.1:1 in 1977–88 to 3.0:1 in 1993–2004, with an intermediary ratio of 4.0:1 in 1989–92. Again, similar secular trends applied for each age category. Epidemiological differences Multivariable logistic regression indicated that predictors of glandular as opposed to squamous cell cancers included an age at diagnosis of less than 70 years, residing in a higher socio‐economic area, and having a more recently diagnosed cancer (at least during the 1977–2000 period) (see Table 4 ). Age categories under 70 years were combined because including them separately did not increase model fit. Their predictive effects by histology type were observed during model development to be very similar. Meanwhile, the relative ratios (95% confidence limits) of glandular to squamous lesions were low at 0.43 (0.20–0.91) for females born in Southern Europe and 0.12 (0.02–0.86) for Aboriginal and Torres Strait Islander women. Place of residence was not predictive of histology type ( p >0.10 ), irrespective of whether it was expressed as statistical subdivision or more broadly as metropolitan or non‐metropolitan. 4 Relative ratios (95% confidence limits) of glandular cancers (adeno/adenosquamous cell carcinomas) to squamous cell carcinomas, by socio‐demographic characteristic and diagnostic period: invasive cervical cancers, South Australia, 1977–2004. a Multiple logistic regression Characteristic (n=cases) Relative ratio Age at diagnosis (years) Under 70 (reference) ( n=1 ,334) 1.00 70–79 ( n=212 ) 0.65 (0.43–0.96) 80+ ( n=104 ) 0.53 (0.30–0.94) Socio‐economic status Other (reference) ( n=1 ,295) 1.00 High ( n=355 ) 1.46 (1.10–1.93) Country of birth Other (reference) (n=1,572) 1.00 Southern Europe ( n=78 ) 0.43 (0.20–0.91) Race Other (reference) (n=1,620) 1.00 Aboriginal/Torres Strait Islander ( n=30 ) 0.12 (0.02–0.86) Diagnostic period 1977–88 (reference) ( n=874 ) 1.00 1989–92 ( n=244 ) 1.54 (1.08–2.20) 1993–96 ( n=213 ) 2.02 (1.41–2.89) 1997–2000 ( n=183 ) 2.22 (1.53–3.23) 2001–04 ( n=136 ) 1.61 (1.03–2.51) Note: (a) Excluding 10% of cases with missing information on race or country of birth. Survivals Survivals were 72.4% at five years from diagnosis, 69.4% at 10 years, 68.1% at 15 years, and 67.0% at 20 years. The older the age at diagnosis, the lower was the survival ( p <0.001 ), with five‐year figures reducing from 90.3% for those under 30 years to 31.8% for females aged 80 years or more. A survival difference also was evident by histology type ( p <0.001 ), with the highest five‐year survival of 74.4% applying to squamous cell cancers as compared with a corresponding 70.1% for glandular cancers, 45.5% for other histology types, and 59.1% for those of unknown type. Diagnostic period was another predictor of survival ( p <0.001 ), with cases diagnosed in 1985–2003 having a higher five‐year survival of 75.4% as compared with figures of 67.1% for 1981–84 and 65.4% for 1977–80. Multivariable proportions hazards regression confirmed that the relative risk of case fatality increased with older age at diagnosis and was higher for glandular and (more so) ‘other’ histology types than for squamous cell lesions (see Table 5 ). Aboriginal and Torres Strait Islander women had an elevated relative risk (95% confidence limits) of 2.14 (1.17–3.92) when compared with other women. A lower relative risk was evident for cases diagnosed more recently, at 0.74 (0.62–0.89) for 1985–2003 compared with 1977–84. Further analyses by calendar year within 1985–2003 did not reveal a difference in outcome ( p =0.35 ). Place of residence was not predictive of outcome ( p >0.10 ), irrespective of the classification used. 5 Relative risks (95% confidence limits) of case fatality from cervical cancer in South Australia by socio‐demographic characteristic, histology type and diagnostic period, 1977–2003. a Characteristic (n=cases) Relative risk Age at diagnosis (years) Under 40 (reference) ( n=539 ) 1.00 40–49 ( n=391 ) 2.04 (1.48–2.82) 50–59 ( n=266 ) 2.88 (2.08–3.99) 60–69 ( n=320 ) 4.24 (3.15–5.72) 70–79 ( n=217 ) 5.45 (3.98–7.47) 80+ ( n=117 ) 12.62 (8.98–17.72) Histology type Squamous cell carc. (reference) (n=1,436) 1.00 Glandular cell ( n=354 ) 1.34 (1.08–1.66) Other ( n=60 ) 2.54 (1.78–3.64) Race Other (reference) (n=1,820) 1.00 Aboriginal/Torres Strait Islander ( n=30 ) 2.14 (1.17–3.92) Diagnostic year 1977–84 (reference) ( n=579 ) 1.00 1985–2003 (n=1,271) 0.74 (0.62–0.89) Note: (a) Multivariable Cox proportional hazards regression (see text): Date of censoring of live cases – 31 December 2003. Discussion The reduction of 55% in incidence and 59% in mortality between 1977–80 and 2001–04, as indicated by the age‐standardised rates, is consistent with trends for Australia overall and for several economically developed countries. It seems likely that the more detailed trends reported now by histology type apply to Australia as a whole. The 80% increase in incidence between 1977–80 and 1985–88 in females less than 50 years of age is also consistent with trends reported in younger age groups in other Australian, New Zealand, North American, British and Eastern European populations. It has been suggested that this increase may reflect changes in sexual behaviour and HPV transmission, although an effect from changes in screening coverage or data ascertainment by the cancer registry cannot be discounted. By comparison, there was no sign of an increase in older age groups in this study. Irrespective of age, incidence rates declined between 1985–88 and 2001–04. Investigation of factors responsible for incidence declines would require data on age at first intercourse, numbers of sexual partners, other risk factors, and screening practices not routinely collected by cancer registries. Of necessity, our analyses have been restricted to the limited range of data items available through this source. The trends in incidence for all histology types combined were reflected in the data for squamous cell carcinomas. Glandular lesions were smaller in number, which complicated assessments of secular trends, especially by age. Nonetheless, although the difference in rates was not statistically significant ( p >0.05 ), the peak for glandular lesions was in 1985–88 and the lowest incidence in 2001–04, as for squamous cell cancers. National data also point to a relatively low incidence of glandular lesions in recent years, which may reflect an emerging benefit from screening. Although based on small numbers, a downward trend in incidence and mortality was suggested for ‘other’ and unknown histology types. While this may reflect true declines, it is also possible that improvements in coding have played a part. Due to larger reductions in incidence for squamous cell than glandular lesions, the ratio of age‐standardised incidence rates for the former to latter reduced from 5.4:1 in 1977–88 to 2.8:1 in 1993–2004, and a similar trend applied for mortality data. It is evident that glandular lesions have become proportionally more common. In particular, these lesions are proportionally more common in patients from the upper socio‐economic residential areas. By comparison, glandular lesions are less commonly encountered in patients over 70 years of age, Aboriginal or Torres Strait Islanders, and those patients born in Southern Europe. Opportunities to prevent glandular cancers through pre‐invasive detection may be more limited, reducing the proportional contribution of these cancers to total numbers of cervical cancers in less frequently screened sections of the community, such as women over 70 years of age, Aboriginal and Torres Strait Islanders, residents of lower socio‐economic areas, and potentially women born in Southern Europe. Hopefully HPV vaccination will have an important role in the prevention of glandular as well as squamous cancers. Approximately two‐thirds of women with cervical cancer survive their disease 20 years or more after diagnosis. Survivals are higher for younger women, those with squamous cell compared with other cancers, non‐Indigenous than Indigenous women, and women diagnosed in the 1985–2003 period compared with earlier years. Again, the poorer outcomes for glandular lesions highlight the importance of preventing them through vaccination or finding their pre‐invasive precursors through screening. Indigenous women have a death rate from cervical cancer about four to five times that of the non‐Indigenous population in Australia, which reflects their high incidence rates and low cancer case survivals. Opportunities to reduce this inequality through more active targeting of cervical cytology screening and, in the longer term, through vaccination need to be pursued actively. Acknowledgements Staff members of the South Australian Cancer Registry are thanked for the care taken over so many years in the collection of data used in this study.

Journal

Australian and New Zealand Journal of Public HealthWiley

Published: Apr 1, 2007

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