Survival of male breast cancer patients: a population-based study in Osaka, Japan

BACKGROUND: Little information is available on the survival of male breast cancer patients because the disease is extremely rare in men. Recent studies indicated there were no gender-differences in the 5-year survival if patients' age and stage were matched. However, this problem has rarely been studied in Japan. METHODS: Using the Osaka Cancer Registry's data, the 5-year survival was analyzed based on the reported 19,869 cases who lived in Osaka Prefecture excluding Osaka City and were diagnosed in 1975-1997, or who resided in Osaka City and were diagnosed in 1993-1997, because reliable follow-up information was available for them. RESULTS: Breast cancer in males accounted for 0.49% of all cases during 1975-1997. The 5-year relative survivals were 71.1% in men and 81.6% in women. The survival in males decreased over older groups due to a lower proportion of localized stage, but not in females. The survival of males in the regional stage was significantly lower than that of females (49.1 versus 73.7%, P<0.05). Survival of males has increased since 1980-1984, while it has been stable in females. Compared with the survival of patients diagnosed in 1975-1979, male patients diagnosed in 1995-1997 had a noticeably lower risk of death after adjusting for age and cancer stage. CONCLUSIONS: The results suggest male breast cancer patients at the regional stage had a worse 5-year survival rate compared to females. However, this gender-related difference seems to have disappeared with the increased survival of males during the 1990s. Further population-based studies are required with a greater number of male patients diagnosed after 1990.     

Primary human papillomavirus DNA screening for cervical cancer prevention: Can the screening interval be safely extended?

Cytological screening has substantially decreased the cervical cancer incidence, but even better protection may be achieved by primary high‐risk human papillomavirus (hrHPV) screening. In the Netherlands, five‐yearly cytological screening for women aged 30–60 years will be replaced by primary hrHPV screening in 2016. The new screening guidelines involve an extension of the screening interval from 5 to 10 years for hrHPV‐negative women aged 40 or 50 years. We investigated the impact of this program change on the lifetime cancer risks in women without an hrHPV infection at age 30, 35, 40, 45 or 50 years. The time to cancer was estimated using 14‐year follow‐up data from a population‐based screening intervention trial and the nationwide database of histopathology reports. The new screening guidelines are expected to lead to a reduced cervical cancer risk for all age groups. The average risk reduction was 34% and was smallest (25%) among women aged 35 years. The impact of hrHPV screening on the cancer risk was sensitive to the duration from cervical intraepithelial neoplasia grade 2/3 (CIN2/3) to cancer; a small increase in the cancer risk was estimated for women aged 35 or 40 years in case a substantial proportion of CIN2/3 showed fast progression to cancer. Our results indicate that primary hrHPV screening with a ten‐yearly interval for hrHPV‐negative women of age 40 and beyond will lead to a further reduction in lifetime cancer risk compared to five‐yearly cytology, provided that precancerous lesions progress slowly to cancer.     

Does lowering the screening age for cervical cancer in The Netherlands make sense?

Recommendations for the age to initiate cervical cancer screening should be directed towards maximum detection of early cervical cancer. However, the screening programme should do more good than harm. The aim of this analysis was to determine whether the target age for cervical cancer screening should be lowered in view of apparent increases in new cases of invasive cancer below age 30 and in age group 30-44 years in The Netherlands. Therefore, all cervical cancer cases diagnosed between January 1, 1989 and December 31, 2003 were selected from the nationwide population-based Netherlands Cancer Registry. For age group 25-39 years, incidence data were also available for 2004 and 2005. To describe trends, the estimated annual percentage of change and joinpoint analysis were used. Between ages 25 and 28 years, the absolute number of new cases of cervical cancer annually has varied between 0 and 9 per age. Significantly decreasing trends in incidence were observed for age groups 35-39 and 45-49 (p < 0.0001 and p = 0.01, respectively). The annual number of deaths fluctuated with a decreasing trend for age groups 30-34 and 35-39 years (p = 0.01 and p = 0.03, respectively). Because the incidence and mortality rates for cervical cancer among women younger than 30 are low and not increasing, lowering the age for cervical cancer screening is not useful at this time. Although the number of years of life gained is high for every case of cervical cancer prevented, the disadvantages of lowering the screening age would be very large and even become disproportionate compared to the potential advantages.     

A Case-Control Study of the Effectiveness of Cervical Cancer Screening in Osaka, Japan

In the small town of Nose in Osaka, Japan, a population-based screening program for cervical cancer by Papanicolaou smear has been conducted since 1965. In order to evaluate the effectiveness of screening in terms of the reduction of the mortality and the incidence of invasive cervical cancer, two types of case-control studies were carried out. In the first study, the case series consisted of all women who died of cervical cancer under 80 years of age at the time of diagnosis in 1965-1987 (N = 15). For each case, 10 controls were chosen from living residents, matched by year of birth. It showed that the odds ratio (OR) of dying of cervical cancer for screened versus non-screened women was 0.22 (95%CI = 0.03-1.95). In the second study, the case series consisted of all women who were diagnosed as having invasive cancer under 80 years of age at the time of diagnosis in the same period (N = 28). For each case, 10 controls were chosen from living residents without invasive cancer, matched by year of birth and according to whether or not they were screened at the year of the diagnosis of the matched case. It showed that the OR of getting invasive cancer for screened versus non-screened women was 0,41 (95%CI = 0.13-1.29). From these results, it was estimated that 78% of cervical cancer mortality and 59% of invasive cervical cancer incidence among non-screened women could be prevented by cervical cancer screening.     

Frequency of cervical intraepithelial neoplasia treatment in a well-screened population

Treatment of cervical intraepithelial neoplasia (CIN) detectable at screening has helped reduce the incidence of cervical cancer, but has also led to overtreatment. The estimates of overtreatment have often focused on a particular grade of CIN or age group. The aim of this paper was to provide a nationwide population-based estimate of the frequency of CIN treatment per prevented cervical cancer case in a well-screened population. We retrieved the data from the Danish National Population, Patient, Health Insurance, Pathology, and Cancer Registers, and calculated annual age-standardized CIN treatment rates. We estimated the frequency of CIN treatment per prevented cervical cancer case by comparing the cumulative life-time risk of CIN treatment from 1996 onward, with the difference in the cumulative life-time risks of cervical cancer in the prescreening and the screening periods. Since 1996, more than 5,000 CIN treatments were undertaken annually in the population of about 2.2 million women aged 15-84 years, and at present 5.2 CIN treatments are undertaken per 1,000 women aged 20-49. About six women have undergone CIN treatment for each prevented cervical cancer. The frequency of CIN treatment increased after 2004 and at present almost eight women are treated per prevented cervical cancer case. Screening, though effective in reducing the incidence of cervical cancer, leads also to a considerable burden of CIN treatment. Future trends in CIN treatment should be closely monitored.     

Cervical screening participation and risk among Swedish-born and immigrant women in Sweden

Cervical cancer is one of the most common cancers among women worldwide, although cervical screening has reduced the incidence in many high-income countries. Low screening uptake among immigrant women may reflect differences in risk of cervical cancer. We investigated the degree of participation in cervical screening among immigrant and Swedish-born women and their concurrent risk of cervical cancer based on individual information on Pap smears taken both from organized and opportunistic screening. Mean degree of participation in cervical screening was estimated for women between 23 and 60 years from 1993 to 2005, stratified by birth region and age at migration. In Poisson regression models, we estimated relative risks (RRs), incidence rates and incidence rate ratios of cervical cancer for women adhering or not to the cervical screening program. We also assessed effect of adherence to screening on the risk of cervical cancer among immigrant groups compared to Swedish-born women. The degree of participation was 62% and 49% among Swedish-born and immigrant women, respectively, with large variations between immigrant groups. Participation was lowest among those immigrating at older ages. Swedish-born and immigrant women who where nonadherent to the cervical screening program had a fivefold excess risk of cervical cancer compared to adherent women. After adjustment for screening adherence, excess RRs of cervical cancer were statistically significant only for women from Norway and the Baltic States. Participation to screening is lower among immigrant than Swedish-born women, and adherence to the recommended screening intervals strongly prevents cervical cancer.     

No increased risk for cervical cancer after a broader definition of a negative Pap smear

The definition of minimal relevant Pap smear abnormality is crucial for balancing the beneficial effects of screening (prevented mortality) with negative side-effects (the high positivity rate). After inflammation ceased to be defined as a borderline abnormal smear outcome in The Netherlands in 1996, the proportion of these smears dropped from 10% to less than 2%. Because this may have caused a loss in smear sensitivity, we analysed the changes in the incidence of cervical cancer after a negative Pap smear. All negative smears made at ages 30-64 in 1990-1995 (n = 1,546,252) and 1998-2006 (n = 3,552,716), registered in the national registry of histo- and cytopathology (PALGA), were followed for up to 9 years. During follow-up of the 1990-1995 smears, 377 women developed cervical cancer within 5,232,959 woman-years at risk, while during the follow-up of the 1998-2006 smears, 619 women developed cervical cancer within 11,210,675 woman-years at risk. The cumulative incidence after the definition change was not significantly higher than before: e.g. at 6 years, the cumulative incidence for smears made in 1990-1995 was 46 per 100,000 (95% CI: 41-52), and for smears in 1998-2006 was 48 per 100,000 (95% CI: 43-54), p = 0.59. The hazard ratio for 1998-2006 compared to 1990-1995 adjusted for age, number of previous negative smears and history of abnormalities was 0.90 (95% CI: 0.78-1.03). In The Netherlands, a setting with high-quality cytological screening, treating smears with only signs of inflammation as negative leads to a considerably lower positivity rate without increasing the risk for cervical cancer after a negative smear.     

Age‐specific prevalence of HPV16/18 genotypes in cervical cancer: A systematic review and meta‐analysis

The prevalence of HPV16/18 in cervical cancer has been reported to decline with age in some papers. However, whether this decline in proportion of cancers positive for HPV16/18 is consistently observed across studies remains to be elucidated. Thus, the aim of this study was to identify papers reporting data on age‐specific prevalence of HPV16/18 in cervical cancer and to summarize the results. We employed MEDLINE and Embase for a systematic literature search and thereby identified a total of 644 papers published in the period 1999–2015, of which 15 papers, reporting cross‐sectional data, were included for review (11,526 cervical cancers). The prevalence of HPV16/18 in cervical cancer declined significantly with age (ρ = ?0.83, p = 0.04) from 74.8% (95% CI 67.6–80.8) in women aged 30–39 years to 56.8% (95% CI 43.9–68.8) in women aged ≥70 years. As the HPV16/18 positive cancers are prevented in fully vaccinated cohorts, the age‐specific epidemiology of cervical cancer is anticipated to change, with a shift in peak incidence rate to older ages. It will be important for integrated vaccination and screening strategies to consider predicted change in the age‐specific epidemiology of cervical cancer.     

Cervical cancer in the Netherlands 1989-1998: Decrease of squamous cell carcinoma in older women, increase of adenocarcinoma in younger women

Cervical cancer is a preventable disease, occurring in relatively young women. In the Netherlands, population-based cervical screening aims at women aged 30-60 years. We performed a population-based study of the incidence of invasive cervical cancer in the Netherlands to evaluate trends, with emphasis on age at time of diagnosis. Histologic diagnosis was retrieved from the Netherlands Cancer Registry for all women residing in the Netherlands with invasive cervical cancer between January 1, 1989, and December 31, 1998. In this 10-year period, the incidence rate of squamous cell carcinoma decreased significantly from 7.1/100,000 to 6.1/100,000 (p < 0.001), with the greatest decrease in women aged 60-74 (-5.5%). While the overall incidence rate of adenocarcinoma remained stable, it increased in women aged 15-29 (+15.8%) and in women aged 30-44 (+2.5%), though the number of cases was small. For squamous cell carcinoma, the incidence of stage II at diagnosis decreased most (-2.7%). There was no change in stage at diagnosis for adenocarcinoma. Most cases of cervical cancer, 60.5%, were detected between ages 30 and 60 years, i.e., the Dutch screening age interval. Cervical cancer in women below age 30 contributed 5.0% to the total incidence, with 3.0% occurring between ages 27 and 29. Thus, screening for cervical cancer in the Netherlands is associated with a decrease in the incidence of squamous cell carcinoma and adenocarcinoma incidence appears to be increasing in younger women.     

Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?

While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population‐based case–control study to examine whether cervical screening leads to early diagnosis and down‐staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age‐matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non‐attenders. The overall OR comparing women up to date with screening with non‐attenders was 0.46 (95% CI: 0.39–0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15–0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46–1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52–3.62) compared to non‐attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05–0.13); however, the odds doubled 3–5 years after a negative test (OR: 2.30, 95% CI: 1.67–3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas.