Second Primary Cancers after in Situ and Invasive Cervical Cancer

To the Editor: Hemminki et al., 1 on the basis of the uniquely large Swedish Family-Cancer Database, reported an excess of tobacco-related neoplasms, invasive cervix, other female genital tract, anal and bladder cancers in women diagnosed with in situ and invasive cervical cancer. To provide further information on the issue, we up-dated to 1998 our report of incidence of invasive cervical cancer following carcinoma in situ of the cervix, 2 and included a companion analysis of second primary cancers following invasive cervical cancers. Briefly, data for the present report were abstracted from the Vaud Cancer Registry file, which includes incident cases of malignant neoplasms in the canton whose population, according to the 1990 census, was about 600 000 inhabitants. 2 Since 1974, a registration scheme, applying the same standardized rules as for incident malignancies, has been implemented for carcinoma in situ (CIS) of the uterine cervix. 2 After exclusion of all synchronous and other cancers (N = 11 after in situ neoplasm, ie 3 cancers of the breast, 2 of the cervix, 4 of the uterine corpus, 1 of the ovary, and 1 of unspecified genital organs; N = 6 after invasive cervical neoplasms, ie 1 cancer of the breast, 3 of the uterine corpus, and 2 of the ovary), the present updated series comprises a total of 2,681 histologically (at least through a biopsy) confirmed CIS, and 893 invasive cervical neoplasms. The age range was 18–92 years (median age 34 years) for CIS, and 21–98 (median age 60 years) for invasive cervical neoplasms. These cases were actively followed up to the end of 1998 (total number of 33,756 and 6,451 person-years of follow-up for CIS and invasive neoplasms, respectively), for the occurrence of cancer, migration, or death. Calculation of expected numbers was based on site-, age- and calendar year-specific incidence rates, multiplied by the observed number of person-years at risk (standardized incidence ratio, SIR), and the corresponding 95% confidence interval (CI), was based on the exact Poisson distribution. 3 Table 1 gives the number of invasive cancers in selected sites or groups of sites following in situ and invasive cervical cancers, in the overall dataset and in strata of <10 and ≥10 years since original diagnosis of cervical cancer. A total of 150 invasive cancers were observed after an in situ cervical cancer versus 145.8 expected, corresponding to a SIR of 1.03. An excess of cervical cancer was restricted to the 10 years since original diagnosis (SIR = 4.18), and an excess of tobacco-related neoplasms was observed only 10 or more years since original diagnosis (SIR = 1.70). The reduced incidence of breast cancer was similar in the two time periods considered. After invasive cervical cancer a total of 81 cancers were observed versus 62 expected, corresponding to a SIR of 1.31. An excess for other genital sites was larger in the first 10 years since diagnosis of cervical cancer, while an excess of tobacco-related neoplasms was similar in the two time periods considered. The SIR for colorectal cancer after in situ or invasive cervical cancer was 2.18 (95% CI = 0.7–5.1) after 10 or more years following invasive cancer. Table 1: Number of Observed (0) Cases and Standardized Incidence Ratios (SIRs, and Corresponding 95% Confidence Intervals [CI]) for Second Primary Cancer after in Situ and Invasive Cervical Cancers According to Time Since Diagnosis. Vaud, Switzerland, 1974–98This up-dated analysis of the Vaud dataset, including a total number of cases more than twice than previously reported, 2 confirms that the risk of invasive cervical cancer is greatly increased in the 10 years following a diagnosis of in situ cervical cancer, and that of other genital sites and anal cancer is increased following both in situ and invasive cervical cancer, pointing to the role of HPV as common aetiological factor on these neoplasms, 4–6 and stressing the importance of accurate monitoring in the few years following a diagnosis of cervical neoplasm. This study also confirms the existence of an excess of tobacco-related neoplasms following cervical neoplasms, thus supporting the hypothesis of a role of tobacco on cervical carcinogenesis. 7,8 The excess of colorectal and of bladder cancer is also consistent with an effect of radiotherapy on these radiosensitive sites near the cervix, 1,9 particularly 10 or more years since original diagnosis. The data were inadequate to quantify the risk of skin and immune-related (lymphoid) neoplasms following a diagnosis of cervical neoplasm. Acknowledgment The contributions of the Vaud Cancer Registry’s staff are gratefully acknowledged. Fabio Levi Van-Cong Te Lalao Randimbison Carlo La Vecchia