Vulval cancer incidence, mortality and survival in England: age-related trends

Authors

  • J Lai,

    Corresponding author
    1. Public Health England (PHE) Knowledge and Intelligence Team (East Midlands) (formerly Trent Cancer Registry), Sheffield, UK
    • Correspondence: J Lai, Public Health England (PHE) Knowledge and Intelligence Team (East Midlands) (formerly Trent Cancer Registry), 5 Old Fulwood Road, Sheffield S10 3TG, UK. Email jenniferlai@nhs.net

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  • R Elleray,

    1. Public Health England (PHE) Knowledge and Intelligence Team (East Midlands) (formerly Trent Cancer Registry), Sheffield, UK
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  • A Nordin,

    1. East Kent Hospitals University NHS Foundation Trust, Margate, UK
    2. Gynaecological Site Specific Clinical Reference Group (SSCRG), National Cancer Intelligence Network (NCIN), London, UK
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  • L Hirschowitz,

    1. Gynaecological Site Specific Clinical Reference Group (SSCRG), National Cancer Intelligence Network (NCIN), London, UK
    2. Birmingham Women's NHS Trust, Birmingham, UK
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  • B Rous,

    1. National Cancer Registration Service (Eastern) (formerly Eastern Cancer Registry and Information Centre, ECRIC), Cambridge, UK
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  • C Gildea,

    1. Public Health England (PHE) Knowledge and Intelligence Team (East Midlands) (formerly Trent Cancer Registry), Sheffield, UK
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  • J Poole

    1. Public Health England (PHE) Knowledge and Intelligence Team (East Midlands) (formerly Trent Cancer Registry), Sheffield, UK
    2. Gynaecological Site Specific Clinical Reference Group (SSCRG), National Cancer Intelligence Network (NCIN), London, UK
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Abstract

Objective

To explore the trends and age characteristics of vulval cancer incidence, mortality, survival and stage of disease.

Design

Retrospective population-based observational study based on cancer registry and Office for National Statistics data.

Setting

England.

Population

All women diagnosed with vulval cancer, defined by the site of the tumour (ICD-10 code C51).

Methods

Including all C51 cases, Poisson regression was used to test for trends in incidence and mortality rates, and generalised linear modelling was used to test for trends in relative survival. Excluding women with melanomas, basal cell carcinomas and Paget disease, stage was investigated as a percentage of staged data by age.

Main outcome measures

Age-standardised incidence and mortality rates, relative survival rates and stage of disease at diagnosis.

Results

From 1990, there was a statistically significant increase in overall incidence (P = 0.018) and decrease in mortality (P < 0.001). In addition, there were statistically significant increases in overall survival (1-year, P < 0.001; 5-year, P < 0.001). However, from 1990, incidence increased in women aged 20–39 years (P = 0.002), 40–49 and 50–59 years (both P < 0.001) and 60–69 years (P = 0.030) and decreased in women aged 80 years and above (P < 0.001). There were statistically significant decreases in mortality in women aged ≥60 years (P < 0.001), and statistically significant increases in 1-year survival in women aged ≥40 years (P ≤ 0.047) and in 5-year survival in women aged 40–49 and ≥60 years (P ≤ 0.011). Stage patterns by age highlight diagnosis at an earlier stage in younger women and more advanced stage diagnosis in older women.

Conclusion

Survival from vulval cancer has improved and mortality has decreased since 1990. The overall incidence of disease has increased as a result of more new diagnoses in the under 70-year age group.

Introduction

Globally, vulval cancer is a rare gynaecological malignancy. It is estimated that there were 26 800 new cases worldwide in 2002; this represents 3% of all gynaecological cancers.[1] In 2002, incidence rates for vulval cancer ranged from less than 0.3 per 100 000 females in Asia to 1.6 per 100 000 females in North America and Europe.[2] Although based on historical data (1993–97), one study demonstrated a higher incidence in Scotland compared with several other countries (Estonia, USA, Switzerland, China).[3] In England, the Office for National Statistics (ONS) reports that, for 2010, there were 967 new cases and over 300 deaths from vulval cancer.[4] Three-quarters of vulval cancers were diagnosed in women aged 60 years and above.[4]

Vulval cancer has a profound effect on the lives of women diagnosed with the disease. In addition to disease-related mortality risk, survivors often suffer significant morbidity, with a negative impact on their quality of life.[5] Disease- and treatment-related morbidity include lower-limb lymphoedema,[6, 7] sexual dysfunction,[5, 8] groin discomfort[5] and pruritus.[9] Further epidemiological and clinical research is required to identify methods of reducing morbidity and mortality in women with this disease.

Vulval cancer incidence rates have increased in England[10, 11] and worldwide.[12-14] Research has indicated that changes in incidence differ according to age.[14] Excluding regional trends that have been reported by Robinson et al.[10] and Somoye et al.,[11] literature on the trends of vulval cancer in England and the UK is limited. Much of the attention from research has been directed towards the top three gynaecological cancers (ovarian, uterine and cervical), and less attention has focused on vulval cancers which are the next most common gynaecological cancer.[4] Therefore, the objective of this article is to investigate whether there have been age-related changes in the trends of vulval cancer incidence, mortality and relative survival. Differences in the three metrics may be associated with the stage of disease. Thus, in addition, this article examines the stage distribution of vulval cancers by age.

Methods

Definition of vulval cancer and data sources

Cases of vulval cancer were defined with the ICD10 code C51. The incidence, mortality and survival data were obtained from a source that did not separate cases according to tumour morphology, and so all cases with a site code of C51 were included. Data on incidence, mortality and relative survival for England were obtained from the UK Cancer Information Service (UKCIS).

UKCIS obtains information on new cancer cases from Regional Cancer Registries which collect data relating to each new diagnosis of cancer that occurs in their resident populations. Cancer registrations are submitted to ONS for validation and followed up for the vital status of each patient. Data on cancer registrations are compiled into the National Cancer Data Repository (NCDR), and these data are then submitted to UKCIS.

UKCIS obtains mortality data from ONS. Mortality data relate to all deaths registered in which vulval cancer is mentioned as an underlying cause of death. Data are reported according to the calendar year in which the death was registered and not the year death occurred.

Differences in incidence, mortality and survival by age may be associated with the stage of disease. Therefore, stage data were obtained from the NCDR which allowed the identification of cases with different tumour types. Basal cell carcinomas (BCCs), melanomas and Paget disease were removed, as these were primarily skin cancers staged differently from vulval carcinomas. The recording of clinically assigned vulval cancer stage by registries in England during the study period was incomplete. However, the Eastern Cancer Registry and Information Centre (ECRIC) derived the TNM (version 6) classification for 82% of cases (excluding BCCs, melanomas and Paget disease) between 2005 and 2009 from pathology and imaging data feeds, patient notes and direct correspondence from clinicians. These ECRIC data for patients resident in the east of England reflect 10% of the total number of cases (excluding BCCs, melanomas and Paget disease) registered nationally.

Age-standardised incidence and mortality rates

Age-specific rates were applied to a European standard population to calculate directly the age-standardised incidence and mortality rates, expressed as a rate per 100 000 female population; 95% confidence intervals (95% CIs) for the incidence and mortality rates were calculated based on the gamma distribution. This method is most appropriate when rates are based on small counts and does not produce CIs that fall below zero.[15]

Relative survival

Relative survival was calculated using the actuarial method[16]: this method was used in studies such as the EUROCARE cancer epidemiology research project[17, 18] and by the International Cancer Benchmarking Partnership.[19] Relative survival was calculated as a ratio of the observed survival rate in the cancer population over the expected survival rate, if the cohort of patients had the same overall mortality rate as the background population. Expected mortality rates were calculated using annual national life tables to provide the age- and sex-specific mortality profile of the background population for each year of diagnosis. Vulval cancer cases were actively followed up to the end of 2010 for their last known vital status. Cases defined as Death Certificate Only (DCO) were not included in the calculation of relative survival. Relative survival is expressed as a percentage, with a value less than 100 indicating lower than expected survival compared with the general population.

Analysis

Preliminary inspections of the trends were conducted using rolling averages to smooth year-on-year variations. For trends across all ages, 3-year rolling averages were used for incidence (1990–92 to 2007–09), mortality (1990–92 to 2008–10) and relative survival (1-year from 1990–92 to 2007–09, 5-year from 1990–92 to 2003–05). For the age-specific analysis, the age groups were defined as follows: 20–39, 40–49, 50–59, 60–69, 70–79 and 80 years and above. By age group, 3- and 5-year rolling averages were used to examine trends for incidence (1990–92 to 2007–09) and mortality (1990–94 to 2006–10), respectively. For relative survival by age group, 5-year rolling averages were used (1-year from 1990–94 to 2006–10, 5-year from 1990–94 to 2001–05).

Poisson regression models were used to test for trends in incidence and mortality over time. For overall trends, changes in the annual number of cases (or deaths) from 1990 to 2009 (or 2010) were tested adjusting for age (5-year). In addition, annual age-specific trends in the number of cases (or deaths) were tested. For each Poisson model, annual female population estimates were included as an exposure. Cases diagnosed in women aged less than 20 years were removed because of the very small numbers.

To investigate changes in overall and age-specific relative survival over time, the annual rate was modelled using a binomial family generalised linear model, with a logit link function and robust variance estimates. Weights, based on the annual number of women with cancer, were included in each trend model. In two of the age-specific models, the 1-year relative survival estimate for one diagnosis year or more was found to be over 100% (five years for age group 20–39 years varying from 100.05 to 100.07%; 1 year for age group 40–49 years of 100.18%). To allow the model assumptions to be satisfied, these survival estimates were censored at 100%.

Two-tailed statistical significance was set at 5% (P ≤ 0.05). Analyses testing for trends were carried out using Stata Statistical Software: Release 12.[20]

Stage was examined as a percentage of total staged cases by age group and for all ages, and displayed as a bar graph to indicate potential differences by age. Cases in which stage data were unrecorded were included in the ‘missing’ category presented as a percentage of the total cases (staged and missing) for all ages and for each age group.

Results

Overall trends

Overall trends show statistically significant changes in age-standardised vulval cancer incidence (Table 1) and mortality (Table 2). Incidence rates statistically significantly increased (P = 0.018) by 18% from 2.13 per 100 000 female population in 1990–92 to 2.51 in 2007–09. Between 1990–92 and 2008–10, rates of mortality from vulval cancer statistically significantly decreased (P < 0.001) by 25% from 0.85 to 0.64 per 100 000. Between 1990–92 and 2007–09, 1-year relative survival showed a statistically significant improvement (P < 0.001) from 76.3 to 85.2% (Table 3). Between 1990–92 and 2003–05, 5-year survival also statistically significantly improved (P = 0.001) from 61.8% to 69.9% (Table 3).

Table 1. Overall age-standardised and age-specific incidence rates and 95% confidence intervals (CIs), 1990–92 to 2007–09
PeriodAll ages20–39 years40–49 years50–59 years60–69 years70–79 years80+ years
RateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCI
  1. LCI, UCI, lower and upper limits for 95% CIs.

1990–19922.132.042.220.470.380.581.180.971.422.231.912.605.024.535.5611.911.012.824.823.226.4
1991–19932.071.982.160.460.380.571.140.931.362.061.752.414.894.395.4111.610.812.524.623.026.2
1992–19942.112.022.210.400.320.491.180.971.412.221.902.585.044.545.5911.911.112.824.723.126.3
1993–19952.132.042.230.410.330.511.221.011.462.171.862.525.374.845.9311.811.012.724.222.725.8
1994–19962.172.082.270.440.350.531.401.171.652.291.962.645.334.805.8911.810.912.724.222.725.8
1995–19972.172.072.260.370.300.461.521.281.782.332.012.685.364.835.9211.610.812.524.022.525.5
1996–19982.222.122.310.400.320.491.711.451.982.402.082.755.344.815.9012.011.112.923.522.125.1
1997–19992.232.142.330.440.360.541.841.582.132.612.282.975.124.605.6711.911.112.822.821.424.4
1998–20002.242.152.340.480.400.581.801.542.082.732.403.095.104.595.6511.810.912.722.621.124.1
1999–20012.302.212.400.490.400.592.041.762.342.952.613.325.314.795.8711.710.912.621.820.423.3
2000–20022.312.212.410.500.410.601.951.682.242.882.553.255.635.096.2111.610.812.521.420.122.9
2001–20032.402.302.500.500.410.602.091.812.392.992.653.356.065.506.6612.111.213.021.219.922.7
2002–20042.322.232.420.450.370.551.921.662.202.932.603.306.035.486.6211.210.412.121.920.623.4
2003–20052.342.242.440.420.340.512.031.772.323.252.893.635.925.376.5011.110.211.921.420.022.8
2004–20062.322.222.420.490.400.592.141.872.433.383.023.775.555.036.1110.69.811.520.319.021.7
2005–20072.402.312.500.580.480.682.241.962.533.593.223.995.595.076.1411.210.312.019.918.621.3
2006–20082.492.392.590.570.470.682.322.042.613.593.224.006.005.476.5611.410.612.321.219.922.6
2007–20092.512.412.610.570.470.682.362.082.663.693.314.095.965.446.5111.210.412.122.220.923.7
Test for trend P = 0.018 P = 0.002 P < 0.001 P < 0.001 P = 0.030 P = 0.095 P < 0.001
Table 2. Overall age-standardised mortality rates and 95% confidence intervals (CIs), 1990–92 to 2008–10
PeriodRateLCIUCI
  1. LCI, UCI, lower and upper limits for 95% CIs.

1990–19920.850.800.91
1991–19930.810.760.87
1992–19940.750.700.81
1993–19950.730.680.78
1994–19960.710.660.76
1995–19970.700.650.75
1996–19980.660.620.71
1997–19990.660.610.71
1998–20000.650.600.70
1999–20010.680.640.74
2000–20020.680.630.73
2001–20030.680.630.73
2002–20040.670.630.72
2003–20050.650.600.69
2004–20060.630.580.67
2005–20070.590.540.63
2006–20080.610.560.65
2007–20090.600.560.65
2008–20100.640.590.68
Test for trend P < 0.001
Table 3. Overall 1- and 5-year relative survival and 95% confidence intervals (CIs), 1990–92 to 2003–05/2007–09
PeriodOne-yearFive-year
RateLCIUCIRateLCIUCI
  1. LCI, UCI, lower and upper limits for 95% CIs.

1990–199276.374.378.361.859.064.7
1991–199376.374.278.361.758.864.6
1992–199475.773.777.860.757.863.6
1993–199578.676.680.663.260.466.1
1994–199679.277.381.264.261.467.1
1995–199780.478.482.365.762.968.5
1996–199880.578.682.465.762.968.5
1997–199982.280.484.068.065.270.7
1998–200082.580.784.468.665.971.4
1999–200182.981.184.770.868.173.5
2000–200282.981.184.769.066.471.7
2001–200382.881.184.669.867.272.4
2002–200482.680.884.368.165.470.7
2003–200583.181.484.969.967.372.6
2004–200684.282.586.0
2005–200784.883.186.4
2006–200884.983.386.6
2007–200985.283.586.8
Test for trend P < 0.001 P < 0.001

Age-related trends

Age-related incidence

Over the last 20 years, the incidence of vulval cancer has increased with increasing age, and peaked in women aged 80 years and above; 58% of new cases that occurred between 2007 and 2009 were diagnosed in women aged 70 years and above.

Trends from 1990–92 to 2007–09 showed statistically significant increases in the rate of new cases diagnosed in women aged 20–39 (P = 0.002), 40–49, 50–59 (P < 0.001) and 60–69 years (P = 0.030) (Table 1). During this time period, the incidence rate in women aged 40–49 years doubled from 1.18 to 2.36 per 100 000 female population, and in women aged 50–59 years increased by 65% from 2.23 to 3.69 per 100 000 female population. During this time, there were smaller increases in incidence in both women aged 20–39 (0.47–0.57 per 100 000) and 60–69 years (5.02–5.96 per 100 000). The incidence rate for women aged 80 years and above statistically significantly (P < 0.001) decreased by 10% (24.8–22.2 per 100 000); however, incidence rates have fluctuated in recent years.

Age-related mortality

Similar to incidence, since the early 1990s, mortality rates have increased with age and peaked in women aged 80 years and above (Table 4). Between 2006 and 2010, 82% of deaths attributed to vulval cancer occurred in women aged 70 years and above.

Table 4. Age-specific mortality rates and 95% confidence intervals (CIs), 1990–94 to 2006–10
Period20–39 years40–49 years50–59 years60–69 years70–79 years80+ years
RateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCI
  1. LCI, UCI, lower and upper limits for 95% CIs.

1990–19940.030.010.050.120.070.180.590.460.741.561.351.805.074.645.5215.414.516.5
1991–19950.030.010.050.120.070.190.500.380.641.601.381.844.904.485.3514.813.915.8
1992–19960.030.010.050.140.090.210.490.370.621.511.301.744.454.054.8714.313.415.3
1993–19970.020.010.040.130.080.200.400.300.521.561.351.804.383.984.8013.712.814.7
1994–19980.020.010.040.110.060.170.340.240.441.471.261.714.424.024.8413.412.614.3
1995–19990.020.010.040.120.070.180.390.290.511.461.251.694.303.914.7113.012.113.8
1996–20000.020.010.030.140.080.200.440.340.561.321.121.544.273.884.6812.411.613.3
1997–20010.030.010.050.120.070.190.490.380.621.391.181.624.303.914.7212.111.313.0
1998–20020.030.020.050.170.110.240.510.400.641.341.141.564.163.774.5612.111.312.9
1999–20030.040.020.060.210.140.290.550.440.681.351.141.573.963.584.3612.111.312.9
2000–20040.040.020.060.220.150.300.590.480.721.341.141.563.883.514.2812.411.613.3
2001–20050.040.020.070.220.150.300.570.460.701.291.091.503.813.444.2112.111.313.0
2002–20060.040.020.060.190.130.270.530.420.661.201.011.413.663.294.0512.011.212.8
2003–20070.040.020.070.160.100.230.490.390.611.201.011.403.653.284.0511.811.012.6
2004–20080.040.020.060.180.120.250.510.400.631.170.991.373.623.254.0111.710.912.5
2005–20090.040.020.060.150.090.210.470.370.591.171.001.373.523.163.9111.110.411.9
2006–20100.050.020.070.150.100.210.520.410.641.231.041.423.533.173.9111.610.912.4
Test for trend P = 0.111 P = 0.247 P = 0.816 P < 0.001 P < 0.001 P < 0.001

Although based on small numbers, from 1990–94 to 2006–10, mortality rates increased slightly in both women aged 20–39 (0.03–0.05 per 100 000) and 40–49 years (0.12–0.15 per 100 000). Mortality rates statistically significantly decreased for women aged 60–69 (by 21%; 1.56–1.23 per 100 000), 70–79 (by 30%; 5.07–3.53 per 100 000) and 80 years and above (by 25%; 15.4–11.6 per 100 000) (P < 0.001) (Table 4).

Age-related relative survival

For women diagnosed in 2005–09, 1-year survival was at least 95.2% in women aged under 60 years. One-year survival then decreased with age to 72.2% in women aged 80 years and above (Table 5). For women diagnosed in 2001–05, 5-year survival was over 78.5% in those aged under 60 years (Table 6). Five-year survival then decreased to 56.2% in women aged 80 years and above.

Table 5. Age-specific 1-year relative surival and 95% confidence intervals (CIs), 1990–94 to 2005–09
Period20–39 years40–49 years50–59 years60–69 years70–79 years80+ years
RateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCI
  1. LCI, UCI, lower and upper limits for 95% CIs.

1990–199493.389.297.494.791.398.189.185.293.082.178.985.476.573.879.365.862.768.8
1991–199595.592.198.994.090.497.689.785.893.683.480.286.678.575.881.267.264.270.2
1992–199697.294.3100.095.191.998.291.688.295.182.879.586.078.676.081.365.962.968.9
1993–199798.696.6100.796.193.498.893.990.996.984.181.087.279.576.982.267.064.070.0
1994–199898.095.7100.495.692.898.394.591.797.385.082.088.180.778.183.269.066.072.0
1995–199998.195.8100.496.093.598.593.690.896.486.583.589.580.878.283.470.867.973.8
1996–200097.595.0100.096.193.898.593.190.396.085.982.988.980.678.083.170.567.573.5
1997–200197.094.399.796.494.298.692.489.695.286.283.289.182.580.085.071.868.774.8
1998–200296.293.499.194.591.997.292.289.494.986.883.989.783.481.085.971.868.874.8
1999–200396.293.399.195.192.697.691.288.394.086.483.589.382.980.485.471.768.774.8
2000–200496.493.699.395.192.697.690.887.993.687.084.289.783.180.685.671.768.774.7
2001–200595.992.999.095.593.297.891.889.194.487.885.190.583.480.885.971.768.774.7
2002–200696.693.899.496.294.198.392.690.195.189.486.891.982.880.285.371.268.274.2
2003–200797.294.799.797.495.799.193.290.895.588.585.991.182.980.485.571.768.774.7
2004–200896.793.999.497.696.099.294.492.396.589.186.691.684.481.986.971.868.974.7
2005–200996.093.198.897.395.698.995.293.397.189.987.592.384.582.087.072.269.275.1
Test for trend P = 0.433 P = 0.047 P = 0.009 P < 0.001 P < 0.001 P = 0.001
Table 6. Age-specific 5-year relative surival and 95% confidence intervals (CIs), 1990–94 to 2001–05
Period20–39 years40–49 years50–59 years60–69 years70–79 years80+ years
RateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCIRateLCIUCI
  1. LCI, UCI, lower and upper limits for 95% CIs.

1990–199486.280.491.981.675.787.575.369.780.962.958.667.357.353.661.049.845.054.5
1991–199587.982.593.280.774.686.874.869.080.565.060.769.459.555.763.250.345.655.0
1992–199689.584.294.884.178.789.576.871.382.264.560.168.859.555.763.249.745.054.3
1993–199792.387.797.086.381.591.277.872.483.166.261.970.559.455.763.149.244.653.9
1994–199893.689.597.787.182.591.678.873.784.066.962.671.160.456.764.150.445.755.1
1995–199994.490.698.389.585.593.577.572.682.467.162.871.462.859.166.554.149.358.9
1996–200091.486.996.089.685.793.477.272.482.066.061.670.461.958.265.655.150.260.0
1997–200191.887.496.289.685.993.477.472.881.967.363.071.664.060.367.658.053.063.0
1998–200290.586.194.988.384.492.176.672.281.167.763.471.965.261.568.956.751.761.7
1999–200389.284.593.988.284.492.075.871.480.267.463.271.665.461.769.158.653.563.6
2000–200488.983.993.887.984.191.778.474.282.668.664.572.664.260.568.055.951.060.8
2001–200590.385.794.989.285.792.778.574.582.570.966.974.963.760.067.556.251.361.1
Test for trend P = 0.332 P = 0.001 P = 0.431 P < 0.001 P = 0.007 P = 0.011

Since 1990, 1-year relative survival has increased in all age groups (Table 5), with statistically significant increases in women aged 40–49 (P = 0.047), 50–59 (P = 0.009), 60–69, 70–79 (both P < 0.001) and 80 years and above (P = 0.001). Five-year relative survival statistically significantly increased in women aged 40–49 (P = 0.001), 60–69 (P < 0.001), 70–79 (P = 0.007) and 80 years and above (P = 0.011) (Table 6).

Age-related stage of disease

From ECRIC, TNM stage data (excluding BCCs, melanomas and Paget disease) were missing for 18% (n = 69) of all cases (n = 394) from 2005 to 2009 (Figure 1). The proportion missing was highest for women aged 20–39 and 70–79 years (both 26%) and lowest for women aged 60–69 years (17%).

Figure 1.

Vulval cancers (excluding basal cell carcinomas, melanomas and Paget disease) diagnosed between 2005 and 2009, by age group, Eastern Cancer Registry and Information Centre (ECRIC) area (TNM 2000 stage).

Overall, 43% of all staged cases registered by ECRIC were stage I, whereas only 8% of cases were stage IV. The proportion of stage I cancers decreased with increasing age from 71% for women aged 20–39 years to 32% for women aged 80 years and above. The proportions of stage III and IV cancer were generally higher in women aged 50 years and above and lower in younger age groups (Figure 1).

Discussion

Main findings

The results show that the overall incidence and survival have increased significantly and mortality has decreased significantly over the 20-year period. However, there were important differences between age groups.

Incidence rates were lower in younger than in older women; however, over time, incidence rates increased significantly in women aged 20–69 years and decreased significantly in women aged 80 years and above. Therefore, the overall increase in incidence was the result of an increasing incidence among younger women.

Mortality rates remained particularly low in younger women relative to older women. However, mortality trends over the last 20 years have only decreased significantly in women aged 60 years and above. Generally, 1- and 5-year survival rates improved for all age groups, although not significantly for women aged 20–39 and 50–59 years (5-year survival only). For the most recent period, survival among women under 60 years was higher than survival in older women. Higher proportions of cases with advanced disease were identified in older women.

Strengths and weaknesses of this study

To our knowledge, this is the first article to document vulval cancer trends using population-based data from England. The use of national, population-based data means that the results are representative of the English population. Cancer registry data are subject to robust quality assurance and are therefore expected to portray accurate trends in the population.

For the stage analysis, data were obtained for one registry and were only completed for 82% of cases. The use of data based on a sample of the population has been applied in many studies (e.g. Robinson et al.[10] and Hampl et al.[21]). However, one disadvantage with using a sample is that this may not be representative of the whole population; therefore, we cannot accurately determine whether older women present with later stages of disease. These findings may only indicate trends at a population level.

For comparability, BCCs, melanomas and Paget disease were removed from the stage analysis. However, it was not possible to remove these from the incidence, mortality and survival analysis because of data source limitations. The outcomes reported here combine different tumour types which have different prognoses[22, 23] and risk factors.

The use of population-based data theoretically infers that registrations are complete for almost all cancers that occurred in England between 1990 and 2009–10. Supporting this hypothesis, for England in 2010, 97% of all cancers were registered;[4] thus, all but a small percentage of cancer registrations are recorded.

Relative survival is calculated excluding DCO cases; these often have a poorer prognosis and therefore the exclusion of these cases may inflate survival estimates. However, inflated survival as a result of the DCO exclusion has become less problematic as DCO trends decline. Survival from vulval cancer has increased in spite of the possible inflated survival estimates affecting earlier periods, and so survival trends are unlikely to be affected by DCO exclusion.

Interpretation

We have reported incidence, mortality and survival trends of all vulval cancer tumour types; however, the majority of the relevant literature discusses risk factors associated with squamous carcinomas. Therefore, we discuss our findings in parallel with studies that base their sample on squamous carcinomas. As the majority of vulval cancers are squamous carcinomas, it is likely that trends are related to the risk factors of squamous carcinoma.

Exploring the factors that may explain the trends falls outside the scope of this article. However, our findings are discussed in the light of the current literature relating vulval cancer trends with potential explanatory factors.

Overall trends

Increasing trends in incidence mirror trends in the USA[12, 24] and Germany.[14] One UK study reported no change in vulval cancer incidence and mortality.[11] However, these trends were based on older regional data (1960–1999) from the south-east of England. Increasing incidence, decreasing mortality and improvements in survival may be associated with improved diagnosis of cases and the centralisation of cancer care in England[25] from 2000 onwards.[26]

Trends in younger women

Increases in vulval cancer incidence in younger women have been recognised in a number of studies.[14, 27] Differences in the incidence across age groups may be explained by different causal factors in younger than in older women.[27-29] Research has shown that classical vulval intraepithelial neoplasia (VIN),[29, 30] a precursor, and human papilloma virus (HPV) infection,[13, 14, 31-33] a risk factor, are associated with the development of vulval cancer in younger women.

HPV infection is associated with 40–70% of vulval cancers.[34, 35] As a main risk factor for classical VIN,[21, 32, 36] high-risk HPV is associated with more than 90% of cases of VIN.[14, 34] HPV may contribute to increasing VIN rates alongside vulval cancer incidence.[37, 38] Therefore, it is plausible to suggest that increasing vulval cancer incidence may be specifically attributed to rising HPV infection.

Supporting the hypothesis that the increase in vulval cancers among younger women is HPV related, increases have also been observed in other HPV-related cancers, such as head and neck and anal cancers.[35] One report documents a slight, but significant, increase in cervical cancers[39]; however, because of the NHS Cervical Screening Programme, the upward trend is less pronounced. Notwithstanding, increases are most evident among the younger generations, reinforcing the hypothesis that changes in sexual practices among the younger populations are a major contributor to increases in HPV infection and associated cancers.[10] The HPV vaccination programme introduced in the UK in 2008 may have a dual impact on reducing vulval cancer in addition to cervical cancer.

As found in another study,[28] better survival may reflect diagnosis at an earlier stage. Supporting the hypothesis that different aetiological processes affect younger and older women, evidence suggests that younger women with HPV-related cancers have a better survival than women with non-HPV-related cancers. This difference has been found with oropharyngeal[40-42] as well as vulval[43] cancers.

Trends in older women

Lichen sclerosus,[29] lichen planus and differentiated VIN are risk factors for the development of squamous carcinoma in older women. Therefore, decreasing trends in older women may reflect better clinical diagnosis or treatment of the risk factors, such as lichen sclerosus or lichen planus, although further evidence is required to confirm this. Anecdotal evidence suggests that improvements in histological diagnosis have led to increased detection of differentiated VIN; this may influence decreases in invasive disease in older women. Further investigations are required to confirm this hypothesis.

Mortality and survival trends concur with previous studies which report a higher risk of death[38, 44] and lower survival in older women.[28] A number of factors affect a patient's chance of survival and mortality. Older women are at increased likelihood of co-morbidity and, in the case of skin[45] and breast[46] cancers, co-morbidity is positively associated with mortality. As shown for breast,[47, 48] oesophageal and gastric[49] cancers, older women are less likely to undergo active/aggressive treatments. Routes to diagnosis may also influence mortality and survival. Evidence suggests that vulval cancer survival is worse for women (particularly older women) diagnosed via emergency presentation.[50]

Age-related patterns in stage may also reflect poorer survival and increased mortality. In comparison with other studies,[27, 28] we found a higher proportion of older women presenting with advanced stage disease. As more advanced stages of cancer tend to be less amenable to treatment, it follows that mortality is positively associated with stage.[38, 44] Non-HPV-related vulval cancers may have a worse prognosis than HPV-related disease,[43] which may explain the poorer survival rates in older women.

Conclusion

This retrospective population-based study has shown that the incidence of vulval cancer has increased significantly in women aged 20–69 years and has stabilised or decreased in older women in England. Trends in vulval cancer mortality have decreased and survival has improved, particularly in older women. However, comparing the most recent data between age groups, older women still have higher proportions of advanced stage disease, potentially resulting in higher mortality and lower survival. Clinical evidence suggests that there are differing aetiological factors between age groups. We anticipate that the HPV vaccine will reduce the incidence of vulval cancer in younger women over the coming decades. Further research is required to investigate the risk factors and to improve earlier detection of vulval cancers in older women.

Disclosure of interests

The authors have no competing interests to disclose.

Contribution to authorship

JP conceived the idea for the study. RE designed and coordinated the study. JL researched the literature, implemented the data analysis, drafted the initial paper and implemented further revisions to the paper. As part of the writing process, RE contributed to further revisions to the paper, together with JP, AN, LH and BR. JP and CG contributed to the statistical analysis of the trends. All authors approved the final version for submission.

Details of ethics approval

Data sourced from the UK Cancer Information Service (UKCIS) is not provided on a patient-level basis. Although data sourced from the National Cancer Data Repository (NCDR) contains patient identifiable information, cancer registries have legal support to collect data relating to cancer under Section 251 of the NHS Act 394 2006 (and formerly under Section 60 of the Health and Social Care Act 2001). Therefore, ethics approval was not obtained.

Funding

Funding was obtained from the National Cancer Intelligence Network (NCIN) as part of an annual work programme undertaken by the former Trent Cancer Registry; this team is now part of the Public Health England Knowledge and Intelligence Team (East Midlands).

Acknowledgements

We would like to acknowledge the registries in England for the ascertainment, coding and quality assurance of the data.

Mini commentary on ‘Vulval cancer incidence, mortality and survival in England: age-related trends’

CW Helm

St Louis University School of Medicine, St Louis, MO, USA

Vulval cancer (VC) is less common than cancer of the uterus, ovary and cervix, but this is no comfort to those suffering from a disease that can cause death and have a devastating impact on the quality of life. This article reports a retrospective analysis of the incidence, survival and mortality of women diagnosed with VC, and explores trends and age characteristics by examining data from English national and regional registries for the two decades from 1990. The authors report a significant increase in the incidence of VC in women aged 20–69 years and, although there has been a stabilisation or decrease in older women, those aged 70 years or older still have the highest rates. Mortality from VC has decreased significantly for women aged 60 years or older and there have been encouraging improvements in 1- and 5-year relative survivals. Although presenting stimulating information, this report has inevitable drawbacks related to the analysis of registry data. The predominant histological type of VC, squamous cell carcinoma (SCC), could not be identified separately, and therefore the data for incidence, survival and mortality also include the unrelated and very different histologies of basal cell carcinoma, melanoma and Paget's disease. In addition, the staging information available limits the conclusions.

A rising incidence of any cancer is a major concern. The increase in VC in younger women in England concurs with reports from other countries, and was anticipated following the sharply increased incidence of precursor lesions reported in the 1990s (Sturgeon et al. Am J Obstet Gynecol 1992;166:1482–5) If there is a positive outlook, it is that SCC is strongly associated with oncogenic human papillomavirus infection (HR HPV) and widespread vaccination of adolescents against HR HPV should eventually reduce the incidence of HR HPV-related vulvar intraepithelial neoplasia and SCC. This effect would probably be enhanced with new generation vaccines against multiple HR HPV genotypes. As for current sufferers, it appears that VC in young women is not only being diagnosed and treated at an earlier stage but, when HPV-related, may have a better prognosis than non-HPV-related VC which most commonly occurs in older women (Regauer and Reich, Gynecol Oncol 2013;doi: 10.1016/j.ygyno.2013.05.041).

Older women still carry the greatest burden of VC, but the positive news is that the incidence in this age group may be declining whilst survival is improving. Further improvement will depend on concerted efforts in multiple areas, including greater awareness by older women and their doctors, earlier detection, better treatment and continued research. The prevention and treatment of VC and its precursors represent a highly specialist area, and it is likely that women in England will continue to benefit from changes made to the cancer programme in the UK, including centralisation (Yap et al. J Obstet Gynaecol 2011;31:754–8).

This report should help to stimulate continued focus on VC and the allocation of appropriate resources directed towards its prevention and treatment. We have come a long way since the time when the overall 5-year survival for VC was around 10% (Folsome, JAMA 1940;114:1499–1504), but there is still a long way to go.

Disclosure of interests

I have no relevant conflict of interest.

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