Abstract
Introduction
Vulvar cancer is a rare gynecological cancer affecting mostly older women. The aim of this population‐based study was to investigate the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019.
Material and methods
Data were retrieved from the mandatory Swedish Cancer Registry consisting of all women diagnosed with vulvar cancer between 1960 and 2019. Only women with a morphologically verified diagnosis of vulvar cancer were included. The individuals were then further matched with the Swedish Death Registry up until May 31, 2020.
Results
In total, 8499 women were included with the following morphologies: squamous cell carcinoma 7250 (85.8%), malignant melanoma 539 (6.4%), adenocarcinoma 401 (4.8%) and other: 259 (3.1%). More than 50% of vulvar cancer cases occurred in women aged between 65 and 84 years of age. The 5‐year age‐standardized net survival increased from 53.0% (95% confidence interval [CI] 48.9–57.5) in 1960 to 72.1% (95% CI 68.8–75.5) in 2019. The proportion of adenocarcinoma among all cases increased from 2.0% to 8.7% between the 1960s and 2010s and an increase in age‐standardized 5‐year net survival was found for adenocarcinoma.
Conclusions
The age‐standardized incidence of vulvar cancer cases in Sweden was stable between 1960 and 2019. During the study period, an increase in adenocarcinoma and a decrease in malignant melanoma cases was found. Five‐year net survival increased by 20 percent units during the study period. For squamous cell carcinoma, an increased age‐specific 5‐year net survival was observed for all age groups, apart for women aged ≥85.
Keywords: epidemiology, incidence, registry, survival, vulvar neoplasms
This Swedish population‐based study describes the incidence and net survival of vulvar cancer (1960–2019). The age‐standardized incidence of vulvar cancer cases in Sweden in this period was stable: age‐standardized incidence 1.88/100 000 women (1960) and 1.75/100 000 women (2019). During the study period, an increase in adenocarcinoma cases and a decrease in malignant melanoma cases was found. The 5‐year net survival increased by 20 percent units during the study period. For squamous cell carcinomas of the vulva, an increased age‐specific 5‐year net survival was observed for all age groups apart for women aged ≥85.
Abbreviations
- AC
adenocarcinoma
- HPV
human papilloma virus
- ICD
International Classification of Diseases
- MM
malignant melanoma
- SCC
squamous cell carcinoma
Key message.
This Swedish population‐based study describes the incidence and net survival of vulvar cancer from 1960 to 2019. The age‐standardized incidence was 1.88/100 000 women (1960) and 1.75/100 000 women (2019). Overall, there was an almost 20 percent unit increase in 5‐year net survival.
1. INTRODUCTION
Vulvar cancer is one of the rarer of the gynecological cancers and affects mostly older women. In Sweden ~150 women are diagnosed every year with vulvar cancer at a median age of about 75 years. 1 The most common histological type is squamous cell carcinoma, which accounts for 90%–95% of cases, 2 followed by malignant melanoma, which accounts for ~3%–10%. 3 The remaining few cases consist of even rarer tumors, eg sarcoma and basal cell carcinoma. 2 Adenocarcinomas of the vulva are rare and an American study observed an age‐adjusted incidence rate of vulvar adenocarcinoma of 0.3 per 1 000 000 women between 2001 and 2018. 4 Approximately 40% of vulvar cases are human papilloma virus (HPV)‐related, 5 , 6 mostly affecting younger women. 7 The non‐HPV‐related vulvar cancer is often associated with inflammatory conditions such as lichen sclerosus. 8
Treatment practices of vulvar cancer have advanced during the study period and the traditional en bloc vulvectomy with bilateral inguinofemoral lymphadenectomy has been abandoned for a more tailored treatment. 2 Unifocal tumors <4 cm in size with no suspicion of groin metastases, can now be treated with a tumor wide excision and sentinel node biopsy sampling of the groins according to national Swedish guidelines. 9 Adjuvant radiochemotherapy is advocated in situations of narrow tumor margins or groin metastases. 9
The incidence of vulvar cancer has risen in western countries such as England, 10 Australia, 11 USA and Canada, 12 Germany 13 and Denmark. 14 In Germany the incidence increased from 1.7/100 000 to 3.6/100 000 between 1999 and 2011. 13 The incidence in Denmark has been reported to be 3.6/100 000 women. 15 Bray et al. found the highest age‐standardized rates in Harare, Zimbabwe and in German registries of >3/100 000 and the lowest levels of <0.2/100 000 in, for example, Saudi Arabia, Iran and Martinique. 16 Several studies report that the increase has been greatest in younger women under 60 11 or under 70 years of age. 10 , 13 Bray et al. also observed increases in incidence in women <60 years of age. 16 The changes in the demography of vulvar cancer may be due to an increase in HPV‐related cancers. 17
Even though the incidence is increasing, studies of mortality have reported disparate findings. One British study observed decreased overall mortality since the 1990s, 10 whereas an Australian study found that mortality rates were stable in younger women (<60 years of age) but decreased in older women (>60 years of age). 11 A Norwegian study found increased 5‐year survival between 1961 and 2010 in women <80 years of age, but not in older women, 18 whereas a Dutch study on squamous cell carcinoma of the vulva found no change in survival rates from 1989 to 2010. 19 A previous Nordic study detected only small changes in incidence and overall survival in vulvar cancer from 1964 to 2003. 20
The aim of this population‐based study is to describe the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019.
2. MATERIAL AND METHODS
2.1. The Swedish Cancer Registry
The Swedish Cancer Registry was initiated in 1958. It is mandatory for all healthcare providers to report all premalignant, malignant and some benign tumors. Both clinicians and pathologist are required to report all cases independently to ensure the completeness of the registry. Six regional registries oversee the data collection and, once yearly, all data are transferred to the national registry. The coverage rate is >95%. 21 The data reported to the Swedish Cancer Registry are: personal identification number, gender, domicile, date of diagnosis, site of tumor, morphology, stage at diagnosis (since 2004), basis of diagnosis, reporting hospital and department.
The tumor site was coded according to the International Classification of Diseases (ICD)‐7 between 1958 and 1986, in ICD‐9 between 1987 and 1992, according to the ICD for Oncology (ICD‐0/2) between 1993 and 2004, and in ICD‐0/3 from 2005. The codes covering the whole study period have been translated to ICD‐7.
Data regarding morphology are available for the whole period as World Health Organization histology code WHO/HS/CANC/24.1. Since 1993, the morphology was also coded according to ICD‐0/2 up until 2004 and thereafter in ICD‐0/3.
Vulvar cancer stage according to the International Federation of Gynaecology and Obstetrics classification 22 has been registered since 2004. Stage was initially recorded according to the 1994 classification and, since its update, the 2009 classification.
2.2. Participants
All inhabitants of Sweden have a unique personal identification number that enables individual linkage through different registries. The cohort consists of all women diagnosed with vulvar cancer registered in 1960–2019. Only women with a morphological diagnosis of vulvar cancer were included. The individuals were then further matched with the Swedish Death Registry up until May 31, 2020. Regarding other cancer diagnoses, all preceding, concomitant and later registered neoplasms in the National Cancer Registry were identified. Only the first diagnosis of vulvar cancer was included. No exclusion was made for women with previous or subsequent diagnoses of other tumors, so as not to introduce a bias in the results. 23
Tumors were classified according to morphology: squamous cell carcinoma (SCC) C24: 146, malignant melanoma (MM) C24: 176, adenocarcinoma (AC) C24: 096 and other morphologies C24: 046; 056; 076; 116; 126; 196; 446; 506; 536; 666; 676; 686; 696; 706; 716; 726; 776; 796; 876; 896 and 996, see Table S1 for distribution of cases. Women were stratified according to age at diagnosis: 18–54, 55–64, 65–74, 75–84, ≥85 years of age and for the years when diagnosed: 1960–69, 1970–79, 1980–89, 1990–99, 2000–2009, and 2010–2019.
2.3. Net survival analyses
Survival time was calculated from date of diagnosis until date of death, date of emigration or May 31, 2020, whichever occurred first. The survival analyses calculated net survival. Expected survival, stratified by sex, attained age and attained year, was estimated from national mortality tables obtained from the Human Mortality Database (http://www.mortality.org) based on data from the National Board of Health Welfare. To adjust for age, weights from the International Cancer Survival Standards 1 24 were used to enable comparisons of patients diagnosed with cancer during different calendar periods. The age groups were 15–44, 45–54, 55–64, 65–74 and ≥75 years of age with the respective weights: 0.07, 0.12, 0.23, 0.29 and 0.29.
Statistical analyses were performed with STATA ver. 17.1 (StataCorp, College Station, TX, USA). Net survival analyses were performed with the user‐written strs command (https://pauldickman.com/software/strs/). For the modeling of net survival and multivariable analyses, the stpm2 command was used supporting non‐proportional hazards. 25 The fitted lines in the figures are made with “lowess smoothing” (local linear weighted smooth). Analysis of grouped data was performed using the Chi‐square test (https://www.socscistatistics.com/tests/chisquare/default2.aspx).
3. RESULTS
In total, 8616 women were diagnosed with vulvar cancer (C51) during 1960–2019. Of these, only morphological verified tumors were included (n = 8536). Of these, a few women had had several diagnoses of vulvar cancer: one diagnosis (n = 8366), two diagnoses (n = 79) and three diagnoses (n = 4), but only the first diagnosis was included, leaving 8449 women in this cohort.
The distribution of the different morphologies (by C24 coding) was as follows: SCC 7250 (85.8%), MM 539 (6.4%), AC 401 (4.8%) and other, 259 (3.1%). The descriptive data of number of vulvar cancer cases, subtypes, and age and stage at diagnosis are shown in Table 1. More than 50% of vulvar cancer cases occurred in women aged between 65 and 84 years of age.
TABLE 1.
Descriptive data of the patient cohort of women with vulvar cancer between 1960 and 2019 shown in 10‐year cohorts as well as for the whole study period.
| 1960–1969 | 1970–1979 | 1980–1989 | 1990–1999 | 2000–2009 | 2010–2019 | Total | |
|---|---|---|---|---|---|---|---|
| Age at diagnosis, median (IQR) | 68 (59–76) | 72 (63–79) | 73 (64–80) | 75 (65–82) | 75 (62–83) | 74 (64–83) | 73 (63–81) |
| Age at diagnosis, n (%) | |||||||
| 18–54 | 155 (14.8) | 144 (12.8) | 152 (11.7) | 212 (14.2) | 212 (14.2) | 190 (9.9) | 1066 (12.6) |
| 55–64 | 249 (23.8) | 164 (14.6) | 191 (14.7) | 159 (10.7) | 234 (14.9) | 289 (15.1) | 1286 (15.2) |
| 65–74 | 339 (32.4) | 354 (31.6) | 385 (29.6) | 338 (22.7) | 307 (19.5) | 483 (25.2) | 2206 (26.1) |
| 75–84 | 246 (23.5) | 348 (31.0) | 426 (32.7) | 534 (35.8) | 496 (31.6) | 538 (28.1) | 2588 (30.6) |
| 85+ | 59 (5.6) | 112 (10.0) | 148 (11.4) | 248 (16.6) | 321 (20.4) | 415 (21.7) | 1303 (15.4) |
| Total | 1048 (100.0) | 1122 (100.0) | 1302 (100.0) | 1491 (100.0) | 1571 (100.0) | 1915 (100.0) | 8449 (100.0) |
| Morphology, n (%) | |||||||
| Squamous cell carcinoma | 872 (83.2) | 975 (86.9) | 1154 (88.6) | 1294 (86.8) | 1340 (85.3) | 1615 (84.3) | 7250 (85.8) |
| Malignant melanoma | 96 (9.2) | 87 (7.8) | 85 (6.5) | 84 (5.6) | 91 (5.8) | 96 (5.0) | 539 (6.4) |
| Adenocarcinoma | 23 (2.2) | 16 (1.4) | 21 (1.6) | 65 (4.4) | 108 (6.9) | 168 (8.8) | 401 (4.8) |
| Other | 57 (5.4) | 44 (3.9) | 42 (3.2) | 48 (3.2) | 32 (2.0) | 36 (1.9) | 259 (3.1) |
| Total | 1048 (100.0) | 1122 (100.0) | 1302 (100.0) | 1491 (100.0) | 1571 (100.0) | 1915 (100.0) | 8449 (100.0) |
| FIGO stage, n (valid %, total %) | |||||||
| I | ‐ | ‐ | ‐ | ‐ | 251 (38.4, 16.0) | 879 (58.3, 46.1) | 1132 (52.3, 13.4) |
| II | ‐ | ‐ | ‐ | ‐ | 196 (30.0, 12.5) | 201 (13.3, 10.6) | 398 (18.4, 4.7) |
| III | ‐ | ‐ | ‐ | ‐ | 148 (22.6, 9.4) | 312 (20.7, 16.4) | 460 (21.2, 5.4) |
| IV | ‐ | ‐ | ‐ | ‐ | 59 (9.0, 3.8) | 116 (7.7, 6.1) | 175 (8.1, 2.1) |
| Total of valid cases | 0 | 0 | 0 | 0 | 654 (100.0, 41.6) | 1508 (100.0, 79.2) | 2153 (100.0, 25.6) |
| Missing cases | 1048 (100.0) | 1122 (100.0) | 1302 (100.0) | 1491 (100.0) | 917 (n/a, 58.4) | 397 (n/a, 20.8) | 6284 (n/a, 74.4) |
| Total cases | 1048 (100.0) | 1122 (100.0) | 1302 (100.0) | 1491 (100.0) | 1571 (n/a, 100.0) | 1905 (n/a, 100.0) | 8449 (n/a, 100.0) |
Abbreviation: IQR, interquartile range.
The age‐standardized incidence of vulvar cancer is shown in Figure 1. In Figure 1A, the overall age‐standardized incidence for all histological subtypes is shown, and in Figure 1B the age‐standardized incidence is shown for the different histological subtypes of SCC, MM, AC and other. In Figure 1C, the age‐standardized incidences for MM, AC and other subtypes are shown separately in a different scale. Overall, the age‐standardized incidence of vulvar cancer decreased somewhat from 1960 (1.88/100 000 women) to 2019 (1.75/100 000 women) (Figure 1A). The same pattern is observed for SCC, as this is the most common morphological diagnosis, constituting 85.8% of the vulvar cancer cases in this study. Overall, there has been a decrease in malignant melanoma and the group of other vulvar cancers, whereas the age‐standardized incidence of adenocarcinoma has increased (Figure 1C).
FIGURE 1.
Age‐standardized incidence of vulvar cancer (A) per year 1960–2019 including all cases, (B) per morphological subtypes 1960–2019 and (C) by subtype (squamous cell carcinoma excluded) 1960–2019. The fitted lines are made with “lowess smoothing” (local linear weighted smooth).
A subanalysis of adenocarcinoma cases regarding stage and age distribution found that there was no difference between early stage (stage I) and later stages (II–IV) when comparing 2005–2009 with 2010–2019: 9/16 vs 33/48 cases (P = 0.36) (Table S2A). Regarding age there was a change in the age‐distribution of age at diagnosis 18–54 years of age vs ≥85 when comparing 1960–1989 with 1990–2019: 20/24 vs 29/93 cases (P < 0.001) (Table S2B).
The age‐standardized 1‐, 5‐ and 10‐year net survival including all morphologies is shown in Figure 2. Overall, there has been a slight increase in 1‐, 5‐ and 10‐year net survival (Figure 2) with a statistically significant trend. The 5‐year age‐standardized net survival increased from 53.0% (95% confidence interval [CI] 48.9–57.5) in 1960 to 72.1% (95% CI 68.8–75.5) in 2019.
FIGURE 2.
Age‐standardized 1‐, 5‐ and 10‐year net survival including all morphologies of vulvar cancer between 1960 and 2019 in Swedish women.
In Figure 3 the age‐standardized 5‐year net survival in 1960–2015 according to morphology is shown. The largest increase in age‐standardized 5‐year net survival is seen for AC, but an increase was also found for SCC and MM. For the group of other vulvar cancer morphologies, the age‐standardized 5‐year net survival increased up until around 1990, but decreased thereafter (Figure 3).
FIGURE 3.
Age‐standardized 5‐year net survival 1960–2015 according to morphology of vulvar cancer in Swedish women.
In Figure 4 the age‐standardized 5‐year net survival according to stage between 2005 and 2019, including all morphologies, is shown. In general, the lower stages have a higher age‐standardized 5‐year net survival (Figure 4).
FIGURE 4.
Age‐standardized 5‐year net survival according to stage 2005–2015, including all morphologies of vulvar cancer in Swedish women.
In Figure 5 the age‐standardized net survival according to morphology is shown. The AC had the highest age‐standardized net survival followed by SCC, MM and other.
FIGURE 5.
Age‐standardized net survival according to morphology for vulvar cancer between 1960 and 2019 in Swedish women.
Figure 6 displays the age‐specific 1‐ and 5‐year net survival for vulvar cancers (including only SCC) between 1960 and 2019. For this analysis, only SCC histology was chosen, as these cases constitute 85.9% of the total cases included. For all age groups, the age‐specific 1‐ and 5‐year net survival increased between 1960 and 2019; the highest net survival was in the age‐group of 18–54 years and the lowest in the age‐group ≥85 years. For this group of the oldest women, the age‐specific 5‐year net survival was practically unchanged during the study period.
FIGURE 6.
Age‐specific (A) 1‐year net survival for vulvar cancer (only including squamous cell carcinoma) in 1960–2019, and (B) 5‐year net survival for vulvar cancer (only including squamous cell carcinoma) in 1960–2015.
4. DISCUSSION
This population‐based study of vulvar cancer cases from the national Swedish Cancer Registry found that the age‐standardized incidence has been relatively stable between 1960 and 2019 and there has been an overall increase in age‐standardized 5‐year net survival.
In this study, the age‐standardized vulvar cancer incidence was found to be quite stable from 1960 (1.88/100 000 women) to 2019 (1.75/100 000 women). This differs from the incidence found in other studies on the incidence of vulvar cancer from England. 10 Australia, 11 USA and Canada, 12 Germany 13 and Denmark, 14 where an increase in incidence was observed. The overall incidence reported in this study is lower than the reported incidence from nearby Denmark of 3.6/100 000 women. 15 Bray et al. investigated the recorded incidence rates of vulvar cancer and found a 30‐fold variation between countries and observed increasing incidence rates in some high‐income countries, eg Australia, Norway, UK and Slovakia. 16 In some studies, the increase in incidence in vulvar cancer has been proposed to be due to an increase in HPV‐related cancers, 17 as several studies report that the increase has been the greatest in younger women <60 11 , 16 or <70 years of age. 10 , 13
The reasons for observing a relatively stable incidence rate in Sweden and not an increase as observed in other countries are probably multifactorial. Sweden has a healthcare system predominately financed by taxes with the goal to provide equal and good healthcare to all citizens and this has been unchanged during the study period. 26 Whether any change has occurred in the proportion of HPV status of the studied vulvar tumors, cannot be divulged from the registry data, as this information is not available. However, HPV vaccination in Sweden has been a part of the national vaccination program for girls since 2010 27 and for boys since 2020, so any effect of this would probably only be seen for the last part of the study.
The overall age‐standardized 5‐year net survival significantly increased from 53% to 72% at the end of the study period. Earlier stages of the disease had a higher age‐standardized 5‐year survival. A Swedish study on data from the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2012 and 2016 observed that the 5‐year age‐standardized relative survival was 74% and the 5‐year relative survival was 84%, 60%, 54% and 35% for stages I, II, III and IV, respectively. 28 The same SQRGC study found that women at least 80 years old rarely had a complete staging procedure, which may have been due to comorbidity in combination with impaired physical performance. 28 Surgery was the primary treatment modality, but one‐third of stage II patients were treated with definitive radiotherapy. 28 In contrast, only one‐fifth of stage III patients were treated with definitive radiotherapy. 28
Other studies regarding survival have reported disparate findings. A Dutch study on squamous cell carcinoma of the vulva observing no change in survival rates from 1989 to 2010, 19 and a Korean study on vulvar cancer found no substantially improvement in overall 5‐year relative survival between 1999 and 2018. 29 A previous Nordic study on gynecological cancer, detected only small changes in overall survival in vulvar cancer from 1964 to 2003. 20 The survival was somewhat lower in Finland and higher in Norway and Iceland during the study period. 20 In Canada and USA, the 5‐year relative survival of SCC between 1973 and 2010 for USA and between 1992 and 2008 for Canada decreased for all age groups, with a more pronounced decrease among older women. 12 Furthermore, a study from Japan observed that women with vulvar cancer had become older during the study period between 2001 and 2010, and that women were more often diagnosed at later stages of the disease with a subsequent decrease in survival. 30 When comparing these results with an American cohort, the same findings were not observed in the American cohort, where no worsening in survival or changes in stage at diagnosis were observed. 30 Unfortunately, information on stage is only available for the later part of this study in 2000–2019. More women were diagnosed in stage I during the second part of this period from 2010 to 2019, compared with the first part of this period from 2000 to 2009 (58.3% vs 38.4% of women with a valid stage), so this could be one reason for the observed improved survival. Increased use of adjuvant radiochemotherapy may also be a reason for better survival. 31
Cancer survival in Europe has been studied within the EUROCARE study where the 5‐year relative survival for vulvar and vaginal cancer combined between 2000 and 2007, was between 50% and 60%. 32 Differences in survival between different countries may be due to differences in allocation of resources to healthcare, general health status of the population, socioeconomic differences and lifestyle factors, but overall, the advances in cancer management that has occurred seem to have resulted in a general improvement in survival for different cancer diagnoses. 32
A study from Norway found increased 5‐year survival between 1961 and 2010 in women <80 years of age but not in older women. 18 This is similar to the results of this study, where the age‐specific 1‐ and 5‐year net survival for SCC in women ≥85 was the lowest, and the 5‐year net survival remained practically unchanged during the study period, whereas an increase in age‐specific 1‐ and 5 year net survival was observed for the other age groups. In the study from Japan between 2001 and 2010, the number of vulvar cancer cases increased in women ≥80 years of age from 18.0% to 30.6% (P < 0.05) in Japanese women during the study period; this change was not seen in the US validation cohort (25.2% to 27.8%; P = 0.160). 30 Another study from USA in 2001–2018 observed an increase in vulvar SCC in women aged 70–79 years of age at diagnosis, but no change for women ≥80 years of age. 4 The SQRGC study on vulvar SCC observed that fewer women ≥80 years of age did not receive any cancer treatment due, for example, to comorbidity, poor performance status or patients’ wish. 28 For the women ≥80 years of age that received treatment, it was more common for only vulvar excision to be performed (51% vs 28%–34% in other age groups) and fewer of the older women had the sentinel node procedure performed (28% vs 51%; P = 0.003). 28 In that study, the 5‐year relative survival was 50.4% for women ≥80 years of age compared with 84.3% for women <60 years of age (P < 0.001). 28 There are several reasons why standard treatment may not be an option in the treatment of the older women. A Dutch study on vulvar cancer on women with a mean age of 79.7 years of age found that not only high age but also comorbidities, frailty, risk of malnutrition and cognitive impairment may lead to de‐escalated treatment as opposed to standard treatment. 33 However, the same study did not find that the de‐escalated treatment affected survival negatively in the studied group of women with vulvar cancer. 33
The most prevalent morphology in this study was SCC, which constituted almost 86% of cases, MM was the second largest group, followed by AC. A study from Korea between 1999 and 2018 found that SCC made up 51.4% of their vulvar cancer cases, followed by Paget's disease (21.3%) and basal cell carcinoma (8.6%). 29 This distribution is different from that observed in this study and from what has been observed in studies from the USA and Europe. Zhou et al. investigated age‐adjusted incidence rates of vulvar cancer in the USA between 2001 and 2018 and observed that 78.3% were SCC, 1.6% were AC and the remaining 20.0% consisted of other morphologies. 4 In a study from Japan between 2001 and 2010, SCC constituted 72.4% of cases, followed by Paget's disease (14.3%) and AC (5.6%). 30
During the study period a decrease in age‐standardized incidence of MM of the vulva was found, whereas an increase in the age‐standardized incidence of AC was observed. In the USA between 2001 and 2018 the SCC incidence rate increased yearly by 0.96%, AC declined by 1.60% yearly and other morphologies declined 1.31% yearly. 4 For the different morphologies included in this study, the age‐standardized net survival was the highest for AC followed by SCC, MM and other. Shifts in diagnostic criteria during the study period may have affected the incidence of different morphologies. Regarding the group of other vulvar cancers, the change in incidence may be an effect of the different morphologies included in this group. Advances in immunohistochemistry may also have improved and influenced the diagnostic accuracy. 34
An increased relative incidence of vulvar AC from 2.0% to 8.7% of all cases between the first and last time‐period, as well as an increase in age‐standardized 5‐year net survival between 1960 and 2015 for vulvar AC was observed. To the best of our knowledge this has not been reported previously. A subanalysis for AC regarding age and stage distributions did not find a significant change in stage distribution comparing stage I with stages II–IV, but more women aged ≥85 were diagnosed with AC during 1990–2019 than during 1960–1989 compared with women aged 18–54. Despite this increase, the 5‐year net survival increased. The increase in incidence of AC could be due to advances in immunochemistry influencing the diagnosis, as previously discussed, as the increase in AC is mirrored by a decrease in the other group. Case reports of HPV‐associated adenocarcinomas in the vulva have been described. 35 An increase in adenocarcinomas at other locations has been described, eg in the esophagus 36 and cervix, 37 so it could also be that the increase in adenocarcinomas is due to other factors.
This study includes a large number of participants with a long‐term follow‐up and is population‐based with national registry data with mandatory reporting from both clinicians and pathologists. Only morphologically verified cases were included in the study (99.1% of all reported cases). Incidence rates were age‐standardized to the World Standard population (World [WHO 2000–2025] Standard). 38 This makes it possible to compare the results with international data. However, there are no data on individual clinical characteristics apart from what is available in the registry (personal identification number, gender, domicile, date of diagnosis, site of tumor, morphology, stage at diagnosis (since 2004), basis of diagnosis, reporting hospital and department). There are no data regarding risk factors for disease or what treatment the participants have received. For SCC there is no information regarding HPV status. Stage was included in the registry since 2004, which limits the calculation of stage‐specific time trends to the later time periods of the study.
5. CONCLUSION
This population‐based study of vulvar cancer cases in Sweden observed a stable age‐standardized incidence in Sweden between 1960 and 2019. During the study period an increase in AC and a decrease in MM cases was found. Overall, there was an almost 20 percent unit increase in 5‐year net survival. For SCC, an increased age‐specific 5‐year net survival was observed for all age groups apart for women aged ≥85.
AUTHOR CONTRIBUTIONS
LM: Conceptualization, data interpretation, writing – original draft. AS: Conceptualization, data interpretation, writing – review and editing. EH: Conceptualization, methodology, formal analysis, data interpretation, writing – review and editing. PWD: Conceptualization, data acquisition, methodology, data interpretation, writing – review and editing. CB: Conceptualization, supervision, data interpretation, writing – review and editing. All authors approved the final version of the article.
CONFLICT OF INTEREST STATEMENT
The authors have stated explicitly that there are no conflicts of interest in connection with this article.
ETHICS STATEMENT
The study was approved by the Regional Ethical Review Board, Stockholm, Sweden (DNR 2017/641–31/1) on April 19, 2017. All results are presented at group level.
Supporting information
Table S1.
Table S2.
ACKNOWLEDGMENTS
We are grateful to the Swedish Cancer Registry for granting access to their database.
Moberg L, Sundqvist A, Holmberg E, Dickman PW, Borgfeldt C. Vulvar cancer incidence and net survival in Sweden 1960 to 2019: A population‐based national study. Acta Obstet Gynecol Scand. 2024;103:561‐571. doi: 10.1111/aogs.14747
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the Swedish Cancer Registry. Access to the data can be obtained according to the exception in General Data Protection Regulation that allows processing of sensitive personal data for research provided that an ethical permit exists. Raw data are available by applying to the Swedish National Board of Health and Welfare but are not publicly available.
REFERENCES
- 1. Statistical Database of Cancer: Socialstyrelsen (Swedish National Board of Health and Welfare), 2017. Accessed January 31, 2023. https://www.socialstyrelsen.se/en/statistics‐and‐data/statistics/statistical‐databases/
- 2. Alkatout I, Schubert M, Garbrecht N, et al. Vulvar cancer: epidemiology, clinical presentation, and management options. Int J Womens Health. 2015;7:305‐313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Sugiyama VE, Chan JK, Kapp DS. Management of melanomas of the female genital tract. Curr Opin Oncol. 2008;20:565‐569. [DOI] [PubMed] [Google Scholar]
- 4. Zhou WL, Yue YY. Trends in the incidence of vulvar and vaginal cancers with different histology by race, age, and region in the United States (2001–2018). Int J Public Health. 2022;67:1605021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Ngamkham J, Homcha‐Aim P, Boonmark K, Phansri T, Swangvaree SS. Preliminary study on human papillomavirus frequency and specific type‐distribution in vulva cancer from Thai women. Asian Pac J Cancer Prev. 2013;14:2355‐2359. [DOI] [PubMed] [Google Scholar]
- 6. De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta‐analysis. Int J Cancer. 2009;124:1626‐1636. [DOI] [PubMed] [Google Scholar]
- 7. Bigby SM, Eva LJ, Fong KL, Jones RW. The natural history of vulvar intraepithelial neoplasia, differentiated type: evidence for progression and diagnostic challenges. Int J Gynecol Pathol. 2016;35:574‐584. [DOI] [PubMed] [Google Scholar]
- 8. Halonen P, Jakobsson M, Heikinheimo O, Riska A, Gissler M, Pukkala E. Lichen sclerosus and risk of cancer. Int J Cancer. 2017;140:1998‐2002. [DOI] [PubMed] [Google Scholar]
- 9. National Guidelines for Vulvar Cancer in Sweden . Regional Cancer Centers. Published 2020, revised version 2023‐05‐02.
- 10. Lai J, Elleray R, Nordin A, et al. Vulval cancer incidence, mortality and survival in England: age‐related trends. BJOG. 2014;121:728‐738; discussion 739. [DOI] [PubMed] [Google Scholar]
- 11. Barlow EL, Kang YJ, Hacker NF, Canfell K. Changing trends in vulvar cancer incidence and mortality rates in Australia since 1982. Int J Gynecol Cancer. 2015;25:1683‐1689. [DOI] [PubMed] [Google Scholar]
- 12. Akhtar‐Danesh N, Elit L, Lytwyn A. Trends in incidence and survival of women with invasive vulvar cancer in the United States and Canada: a population‐based study. Gynecol Oncol. 2014;134:314‐318. [DOI] [PubMed] [Google Scholar]
- 13. Buttmann‐Schweiger N, Klug SJ, Luyten A, et al. Incidence patterns and temporal trends of invasive nonmelanotic vulvar tumors in Germany 1999–2011. A population‐based cancer registry analysis. PLoS One. 2015;10:e0128073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Baandrup L, Varbo A, Munk C, Johansen C, Frisch M, Kjaer SK. In situ and invasive squamous cell carcinoma of the vulva in Denmark 1978–2007 – a nationwide population‐based study. Gynecol Oncol. 2011;122:45‐49. [DOI] [PubMed] [Google Scholar]
- 15. Olsen J, Jørgensen TR, Kofoed K, Larsen HK. Incidence and cost of anal, penile, vaginal and vulvar cancer in Denmark. BMC Public Health. 2012;12:1082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Bray F, Laversanne M, Weiderpass E, Arbyn M. Geographic and temporal variations in the incidence of vulvar and vaginal cancers. Int J Cancer. 2020;147:2764‐2771. [DOI] [PubMed] [Google Scholar]
- 17. Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on the Status of Cancer, 1975–2009, featuring the burden and trends in human papillomavirus (HPV)‐associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013;105:175‐201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Meltzer‐Gunnes CJ, Småstuen MC, Kristensen GB, Tropé CG, Lie AK, Vistad I. Vulvar carcinoma in Norway: a 50‐year perspective on trends in incidence, treatment and survival. Gynecol Oncol. 2017;145:543‐548. [DOI] [PubMed] [Google Scholar]
- 19. Schuurman MS, van den Einden LC, Massuger LF, Kiemeney LA, van der Aa MA, de Hullu JA. Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer. 2013;49:3872‐3880. [DOI] [PubMed] [Google Scholar]
- 20. Klint A, Tryggvadóttir L, Bray F, et al. Trends in the survival of patients diagnosed with cancer in female genital organs in the Nordic countries 1964–2003 followed up to the end of 2006. Acta Oncol. 2010;49:632‐643. [DOI] [PubMed] [Google Scholar]
- 21. Barlow L, Westergren K, Holmberg L, Talbäck M. The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol. 2009;48:27‐33. [DOI] [PubMed] [Google Scholar]
- 22. Hacker NF, Barlow EL. Staging for vulvar cancer. Best Pract Res Clin Obstet Gynaecol. 2015;29:802‐811. [DOI] [PubMed] [Google Scholar]
- 23. Rosso S, De Angelis R, Ciccolallo L, et al. Multiple tumours in survival estimates. Eur J Cancer. 2009;45:1080‐1094. [DOI] [PubMed] [Google Scholar]
- 24. Corazziari I, Quinn M, Capocaccia R. Standard cancer patient population for age standardising survival ratios. Eur J Cancer. 2004;40:2307‐2316. [DOI] [PubMed] [Google Scholar]
- 25. Lambert PC, Royston P. Further development of flexible parametric models for survival analysis. Stata J. 2009;9:265‐290. [Google Scholar]
- 26. Janlöv NBS, Glenngård AH, Hanspers K, Anell A, Merkur S. Sweden Health System Review. Health Systems in Transition, Vol. 25 . European Observatory on Health Systems and Policies; 2023. [PubMed]
- 27. Wang J, Herweijer E, Nordqvist Kleppe S, et al. High coverage and adherence to dose intervals of the national school‐based HPV vaccination program in Sweden during 2012–2019. Prev Med Rep. 2023;35:102342. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Hellman K, Holmberg E, Bjurberg M, et al. Primary treatment and relative survival by stage and age in vulvar squamous cell carcinoma: a population‐based SweGCG study. Gynecol Oncol. 2020;159:663‐671. [DOI] [PubMed] [Google Scholar]
- 29. Shin DW, Bae J, Ha J, Lee WM, Jung KW. Trends in incidence and survival of patients with vulvar cancer in an Asian country: analysis of the Korean Central Cancer Registry 1999–2018. Gynecol Oncol. 2022;164:386‐392. [DOI] [PubMed] [Google Scholar]
- 30. Nishio S, Matsuo K, Shibata T, et al. Changes in the clinicopathological demographics of vulvar cancer in Japan: increasing oldest‐old, stage shifting, and decreasing cohort‐level survival. J Clin Med. 2019;8:2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Olawaiye AB, Cuello MA, Rogers LJ. Cancer of the vulva: 2021 update. Int J Gynaecol Obstet. 2021;155(Suppl 1):7‐18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. De Angelis R, Sant M, Coleman MP, et al. Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE‐5—a population‐based study. Lancet Oncol. 2014;15:23‐34. [DOI] [PubMed] [Google Scholar]
- 33. Gans EA, Portielje JEA, Dekkers OM, et al. Frailty and treatment decisions in older patients with vulvar cancer: a single‐center cohort study. J Geriatr Oncol. 2023;14:101442. [DOI] [PubMed] [Google Scholar]
- 34. Saikia B, Gupta K, Saikia UN. The modern histopathologist: in the changing face of time. Diagn Pathol. 2008;3:25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Voltaggio L, McCluggage WG, Iding JS, Martin B, Longacre TA, Ronnett BM. A novel group of HPV‐related adenocarcinomas of the lower anogenital tract (vagina, vulva, and anorectum) in women and men resembling HPV‐related endocervical adenocarcinomas. Mod Pathol. 2020;33:944‐952. [DOI] [PubMed] [Google Scholar]
- 36. McColl KEL. What is causing the rising incidence of esophageal adenocarcinoma in the west and will it also happen in the east? J Gastroenterol. 2019;54:669‐673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Sundqvist A, Moberg L, Dickman PW, Hogberg T, Borgfeldt C. Time trends for incidence and net survival of cervical cancer in Sweden 1960–2014 – a Nationwide population‐based study. Cancer Epidemiol Biomarkers Prev. 2022;31:1572‐1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Ahmad OB, Boschi Pinto C, Lopez AD. Age standardization of rates: a new WHO standard. GPE Discussion Paper Series. 2001;31:10‐12. [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1.
Table S2.
Data Availability Statement
The data that support the findings of this study are available from the Swedish Cancer Registry. Access to the data can be obtained according to the exception in General Data Protection Regulation that allows processing of sensitive personal data for research provided that an ethical permit exists. Raw data are available by applying to the Swedish National Board of Health and Welfare but are not publicly available.