Outcomes for women without conventional treatment for stage 1A (microinvasive) carcinoma of the cervix.

BACKGROUND: An unethical clinical study that entailed withholding treatment from women diagnosed with cervical intraepithelial neoplasia 3 (CIN3) was conducted at National Women's Hospital, Auckland, New Zealand. Women with microinvasive carcinoma of the cervix also had treatment withheld. AIMS: To describe the management and outcomes for women with microinvasive carcinoma for many of whom conventional treatment was withheld. MATERIALS AND METHODS: Retrospective cohort study of women with a diagnosis of stage 1A cervical carcinoma at National Women's Hospital. Medical records, cytology and histopathology were reviewed and data linked with cancer and death registries up to December 2000. RESULTS: Between 1955 and 1976, 62 women were initially diagnosed with stage 1A cervical cancer and 20 were diagnosed during follow up (to 1995). Sixty of the 82 women had initial management characterised as 'probably non-curative'; 20 of these received only a small diagnostic excision. Women in the latter group were more likely to: (i) subsequently have positive cytology (P < 0.0005), (ii) have untreated positive cytology (P = 0.02), and (iii) undergo multiple biopsies after initial management (P = 0.001). Of the women who received only a small diagnostic excision, eight of 20 developed invasive carcinoma of the cervix (≥ stage 1B) or vaginal vault, compared to two of 22 women who received initial treatment characterised as 'probably curative'. CONCLUSIONS: Women with microinvasive carcinoma were included in a natural history study of CIN3; they underwent numerous procedures designed to observe rather than treat their condition, and had a substantial risk of invasive cancer.

Prevalence of KISS1 Receptor mutations in a series of 603 patients with normosmic congenital hypogonadotrophic hypogonadism and characterization of novel mutations: a single-centre study.

STUDY QUESTION: What is the exact prevalence of Kisspeptin Receptor (KISS1R) mutations in the population of patients with normosmic congenital hypogonadotrophic hypogonadism (nCHH) by comparison with other genes, involved in gonadotrophin-releasing hormone (GnRH) release or action? SUMMARY ANSWER: KISS1R mutants are responsible for the nCHH phenotype in only a small minority of cases and were less prevalent than GnRH Receptor (GNRHR) mutations. WHAT IS KNOWN ALREADY: The respective prevalence of each of the genetic causes of nCHH is unclear. Large series of patients are very rare and suffer from heterogeneity of the population of CHH studied. STUDY DESIGN, SIZE, DURATION: Patients with nCHH were consecutively enrolled in a single French referral centre and were gradually tested for KISS1R between January 2006 and April 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 603 patients with nCHH (399 men and 204 women) were diagnosed at the Bicêtre Hospital and underwent KISS1R analysis. The GNRHR, tachykinin receptor 3 (TACR3), gonadotrophin-releasing hormone 1 (GNRH1), tachykinin 3 (TAC3) and KISS1 genes were also sequenced. Functional characterization of KISS1R mutations included a study of signal transduction using a reporter gene (serum response element-luciferase (SRE-Luc) involved in the mitogen-activated protein (MAP) kinase pathway. MAIN RESULTS AND THE ROLE OF CHANCE: We detected 15 KISS1R variants (10 novel), in 12 of the 603 patients (2.0%, 95% CI [0.9-3.1]. KISS1R mutations were less prevalent than GNRHR (4.7%) and TACR3 (2.6%) mutations but more prevalent than GNRH1 (1.5%), TAC3 (1.0%) and KISS1 (0%) mutations. KISS1R mutants were present in the biallelic state in 8 of the 12 patients concerned. Among 5 men with biallelic KISS1R mutations, 4 had either micropenis or cryptorchidism. In vitro analysis of the 5 new variants present in the biallelic state (C95W, Y103*, C115W, P176R and A287E) showed a loss of function. LIMITATIONS, REASONS FOR CAUTION: The prevalence of TACR3, GNRH1, TAC3 and KISS1 mutations was calculated from a smaller number of nCHH patients than KISS1R and GNRHR. This should prompt caution concerning the reported prevalence of mutations in these four genes. WIDER IMPLICATIONS OF THE FINDINGS: We show that KISS1R mutants are responsible for the nCHH phenotype in only a small minority of cases. Together, the genes analysed here were mutated in fewer than 15% of patients, suggesting a role of other genes in nCHH. The presence of cryptorchidism and/or micropenis in the majority of men with biallelic KISS1R mutations strongly suggests that this gene is essential for prenatal GnRH secretion. STUDY FUNDING, COMPETING INTERESTS: This work was supported in part by grants from Paris-Sud University (Bonus Qualité Recherche, and Attractivité grants) to J.B., French Ministry of Health, Hospital Clinical Research Program on Rare Diseases. Assistance Publique Hôpitaux de Paris, Programme Hospitalier de Recherche Clinique (PHRC # P081212 HYPOPROTEO) to J.Y. C.P. was supported by student fellowships 'Année Recherche' from Agence Régionale de Santé Provence Alpes Côtes d'Azur. The authors have nothing to disclose.

The Rationalization of Unethical Research: Revisionist Accounts of the Tuskegee Syphilis Study and the New Zealand "Unfortunate Experiment".

Two studies, widely condemned in the 1970s and 1980s-the Tuskegee study of men with untreated syphilis and the New Zealand study of women with untreated carcinoma in situ of the cervix-received new defenses in the 21st century. We noted remarkable similarities in both the studies and their defenses. Here we evaluate the scientific, political, and moral claims of the defenders. The scientific claims are largely based on incomplete or misinterpreted evidence and exaggeration of the uncertainties of science. The defenders' political arguments mistakenly claim that identity politics clouded the original critiques; in fact such politics opened the eyes of the public to exploitation. The moral defenses demonstrate an overreliance on codes of conduct and have implications for research ethics today.

A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use.

The magnitude of the suspected increase in risk of acute interstitial nephritis among proton pump inhibitor users is uncertain. Here, we conducted a nested case-control study using routinely collected national health and drug dispensing data in New Zealand to estimate the relative and absolute risks of acute interstitial nephritis resulting in hospitalization or death in users of proton pump inhibitors. The cohort included 572,661 patients without a history of interstitial nephritis or other renal diseases who started a new episode of proton pump inhibitor use between 2005 and 2009. Cases had a first diagnosis after cohort entry of acute interstitial nephritis confirmed by hospital discharge letter or death record, and renal histology (definite, 46 patients), or discharge letter or death record only (probable, 26 patients). Ten controls, matched by birth year and sex, were randomly selected for each case. In the case-control analysis based on definite cases and their controls, the unadjusted matched odds ratio (95% confidence interval) for current versus past use of proton pump inhibitors was 5.16 (2.21-12.05). The estimate was similar when all cases (definite and probable) and their corresponding controls were analyzed, and when potential confounders were added to the models. The crude incidence rates and confidence intervals per 100,000 person-years were 11.98 (9.11-15.47) and 1.68 (0.91-2.86) for current and past use, respectively. Thus, current use of a proton pump inhibitor was associated with a significantly increased risk of acute interstitial nephritis, relative to past use.

HSV-2 incidence by sex over four age periods to age 38 in a birth cohort.

OBJECTIVES: To examine herpes simplex virus type 2 (HSV-2) incidence over four periods to age 38 in a birth cohort, and to compare risks for men and women, taking into account sexual behaviour. METHODS: At ages 21, 26, 32 and 38, participants in the Dunedin Multidisciplinary Health and Development Study were invited to provide serum for HSV-2 serology, and information on sexual behaviour. HSV-2 incidence rates were calculated for four age periods, and comparisons made by sex and period, taking into account number of sexual partners. RESULTS: By age 38, 17.3% of men and 26.8% of women had ever been seropositive for HSV-2. Incidence peaked for women from age 21 to 26 (19.1 per 1000 person-years) and men from age 26 to 32 (14.1 per 1000 person-years); it fell markedly for both from age 32 to 38 (5.1 and 6.8 per 1000 person-years for men and women, respectively). Overall risk was significantly higher for women: adjusted incidence rate ratio 1.9 (95% CI 1.4 to 2.7); the sex difference was most marked from age 21 to 26 (3.4, 95% CI 1.9 to 6.3). CONCLUSIONS: Our findings are consistent with a greater biological susceptibility to HSV-2 among women, and with the increasing risk to the early/mid-20s for women and late 20s/early 30s for men, being driven by an increasing pool of prevalent infection. The reduced risk in the mid-30s is consistent with declining infectivity of long-term prevalent infections.

Stability and change in same-sex attraction, experience, and identity by sex and age in a New Zealand birth cohort.

Gaps remain in knowledge of changes in sexual orientation past adolescence and early adulthood. A longitudinal study of a New Zealand birth cohort was used to examine differences by age and sex in change in sexual attraction between 21 (1993/1994) and 38 years (2010/2011), sexual experiences between 26 and 38 years, and sexual identity between 32 and 38 years. Any same-sex attraction was significantly more common among women than men at all ages. Among women, any same-sex attraction increased up to age 26 (from 8.8 to 16.6 %), then decreased slightly by age 38 (12.0 %); among men, prevalence was significantly higher at age 38 (6.5 %) than 21 (4.2 %), but not in the intermediate assessments. It is likely that the social environment becoming more tolerant was responsible for some of the changes. Same-sex attraction was much more common than same-sex experiences or a same-sex identity, especially among women, with no major sex differences in these latter dimensions. Women exhibited much greater change in sexual attraction between assessments than men; for change in experiences and identity, sex differences were less marked and not statistically confirmed. Changes in the respective dimensions appeared more likely among those initially with mixed attraction and experiences, and among those initially identifying as bisexual, but this did not account for the sex difference in likelihood of change. These results provide contemporary information about the extent and variation of reported sexual attraction, experiences, and identity that we show continues across early and mid-adulthood.

The relationship between multiple sex partners and anxiety, depression, and substance dependence disorders: a cohort study.

Changes in sexual behavior have resulted in longer periods of multiple serial or concurrent relationships. This study investigated the effects of multiple heterosexual partners on mental health, specifically, whether higher numbers of partners were linked to later anxiety, depression, and substance dependency. Data from the Dunedin Multidisciplinary Health and Development Study, a prospective, longitudinal study of a birth cohort born in 1972-1973 in Dunedin, New Zealand were used. The relationship between numbers of sex partners over three age periods (18-20, 21-25, and 26-32 years) and diagnoses of anxiety, depression, and substance dependence disorder at 21, 26, and 32 years were examined, using logistic regression. Interaction by gender was examined. Adjustment was made for prior mental health status. There was no significant association between number of sex partners and later anxiety and depression. Increasing numbers of sex partners were associated with increasing risk of substance dependence disorder at all three ages. The association was stronger for women and remained after adjusting for prior disorder. For women reporting 2.5 or more partners per year, compared to 0-1 partners, the adjusted odd ratios (and 95 % CIs) were 9.6 (4.4-20.9), 7.3 (2.5-21.3), and 17.5 (3.5-88.1) at 21, 26, and 32 years, respectively. Analyses using new cases of these disorders showed similar patterns. This study established a strong association between number of sex partners and later substance disorder, especially for women, which persisted beyond prior substance use and mental health problems more generally. The reasons for this association deserve investigation.

The destination of Pacific Island health professional graduates from a New Zealand university.

BACKGROUND: There is a shortage of health professionals in Pacific Island states and territories, and a need in New Zealand for Pacific health professionals to serve Pacific communities. METHODS: A cross-sectional postal survey was conducted to investigate retention of Pacific graduates. All graduates of Pacific ethnicity or nationality from the University of Otago in the years 1994 to 2004 in medicine, dentistry, pharmacy, physiotherapy and medical laboratory science were included. RESULTS: The response rate was 59% (75 out of 128). Only 7% of respondents were working in the Pacific Islands (12% of non-residents and 4% of New Zealand residents), though the proportion in the whole cohort could be up to 20%. One third intended to work in Pacific communities in New Zealand or the Pacific Islands in the future. Factors that would favour such an intention were an adequate income, job availability, and good working conditions. CONCLUSIONS: Retention of graduates in the Pacific Islands is poor and measures to improve retention are needed.

Traumatic and non-traumatic spinal cord impairment in New Zealand: incidence and characteristics of people admitted to spinal units.

This paper estimates the incidence (all ages) of spinal cord neurological impairment (SCI; traumatic and non-traumatic) in New Zealand and describes pre-SCI characteristics and early post-SCI outcomes for participants (16-64 years) in this longitudinal study. Demographic and clinical data on all people admitted to New Zealand's two spinal units (mid-2007 to mid-2009) were included for the estimate of incidence. Participants in this longitudinal study were asked at first interview about pre-SCI socio-demographic, health and behavioural characteristics, and about post-SCI symptoms, general health status (EQ-5D) and disability (WHODAS 12-item). Age-adjusted incidence rates (95% CI) for European, Maori, Pacific and 'Other' ethnicities were 29 (24-34), 46 (30-64), 70 (40-100) and 16 (9-22) per million, respectively. Interviews with 118 (73%) participants (16-64 years), occurred 6.5 months post-SCI. Most reported bother with symptoms, and problems with health status and disability. Compared with Europeans, the incidence of SCI is high among Maori and particularly high among Pacific people. Six months after SCI, proximate to discharge from the spinal units, considerable symptomatic, general health and disability burden was borne by people with SCI.

Consistency and reliability of self-reported lifetime number of heterosexual partners by gender and age in a cohort study.

BACKGROUND: The reported number of sexual partners is a variable used extensively in sexual health research. However, the reliability and consistency of this measure, and the statistical assessment of these attributes, are not well understood. METHODS: Using data at ages 21, 26, and 32 years from a New Zealand birth cohort, we compared responses on the lifetime number of heterosexual sex partners to assess reliability and consistency. Differences by gender and age were considered, and the effect of number of sexual partners. A variety of analytical methods were used to explore statistical challenges of these data including variance estimation, fractional polynomial transformations, and quantile regression. RESULTS: We found some level of discrepancy between reports of the number of sexual partners when assessed at different times is common, driven by those reporting a high number of partners who were disproportionately men. Men reported a higher lifetime number of partners than women at each age, and there were statistically significant differences by gender in (a) consistency between reports at different ages, and (b) reliability of reports as measured by both the Intraclass Correlation Coefficient and the Kappa statistic. CONCLUSIONS: When considering reliability, multiple statistical approaches are necessary or conclusions can be misleading. Variance components should be examined when considering the Intraclass Correlation Coefficient. When modelling, robust methods like fractional polynomials and quantile regression should be employed to accommodate nonlinearity. Sensitivity analyses excluding participants whose partner number is in the upper 5% to 25% are informative, as these were shown to have the highest discrepancies.

Perceived "out of control" sexual behavior in a cohort of young adults from the Dunedin Multidisciplinary Health and Development Study.

Out of control sexual behavior, also known as compulsive sexual behavior or sexual addiction, has not been studied in a representative sample of the general population. At age 32 years, 940 (93%) of 1,015 members of the birth cohort of the Dunedin Multidisciplinary Health and Development Study responded to a series of questions about sexual behavior, administered by computer. We enquired about sexual fantasies, urges or behavior that participants regarded as out of control during the previous year, and defined such experiences as out of control sexual experiences (OCSE). Nearly 13% of men and 7% of women reported OCSE in the past year. Women who reported such experiences were more likely than other women to have reported (elsewhere in the interview) having had high numbers of opposite sex partners, concurrent sexual relationships, or sex with a partner met on the internet, as well as a higher likelihood of same-sex attraction or behavior. Among men reporting OCSE, there was an association with having paid for heterosexual sex and with same-sex attraction and behavior. Few believed that OCSE had interfered with their lives (3.8% of all men and 1.7% of all women in the cohort). Only 0.8% of men and 0.6% of women reported that their actual sexual behavior had interfered with their lives. OCSE were also analyzed in relation to certain personality traits and to childhood sexual abuse (CSA). Some evidence of a link with impulsivity (women only) and negative affectivity was found. CSA was associated with OCSE among men. In conclusion, this population-based study has provided the first empirical estimations of the occurrence of OCSE and its relationship to a range of sexual behaviors in a representative sample.

A longitudinal study of the life histories of people with spinal cord injury.

BACKGROUND: Approximately 70-80 New Zealanders have spinal cord impairment (SCI) due to injury (2/3) or disease (1/3) each year. They had been socialized as non-disabled people. Following paralysis, interrelationships between body, self and society change. Little is known of the impact of these changes on life histories, life chances and life choices of people with SCI. This has negative implications for the design of rehabilitation and disability support services in New Zealand. Furthermore, the trajectory of disability is affected by previous socioeconomic conditions. How specific supports following SCI (eg, rehabilitation and compensation funded by the Accident Compensation Corporation; ACC) can change this trajectory is unknown. OBJECTIVES: To explore the interrelationships of body, self and society for people with SCI and how these have shaped life chances, life choices and subjectivity. To investigate how entitlement to rehabilitation and compensation through ACC affects socioeconomic and health outcomes. SETTING: New Zealand. DESIGN: A prospective cohort study; mixed methods. PARTICIPANTS: 112 people with SCI admitted for the first time to one of New Zealand's two spinal units without serious cognitive injury. DATA: Structured interviews with all participants (n=112); qualitative interviews with a selected subgroup (n=20); clinical data collected at the time of admission. Exposures include: demographics, comorbidity, previous health and socioeconomic status, SCI resulting from illness or injury, income support, health and social services. OUTCOME MEASURES: Socioeconomic status, health, participation and life satisfaction. ANALYSIS: Descriptive statistics; differences tested by paired t tests or McNemar tests; multiple regression and mixed models. Qualitative analysis will be interpretive.

Consequences in women of participating in a study of the natural history of cervical intraepithelial neoplasia 3.

BACKGROUND: A retrospective cohort study was performed in 1063 women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (previously termed carcinoma in situ- CIS) in the National Women's Hospital, Auckland, New Zealand. The study describes the clinical management and outcomes for women with CIN3 diagnosed in the decade of 1965-1974, when treatment with curative intent was withheld in an unethical clinical study of the natural history of CIS. A comparison is made with women who were diagnosed earlier (1955-1964) and later (1975-1976). AIMS: The aim of the study is to record the medical encounters, frequency and management of cytological abnormalities and the occurrence of invasive cancers. The medical records, cytology and histopathology were reviewed and data linked with cancer and death registers. RESULTS: Women diagnosed with CIN3 in 1965-1974 (n = 422), compared with those diagnosed earlier (n = 385) or later (n = 256): (i) were less likely to have initial treatment with curative intent (51% vs 95 and 85%, respectively); (ii) had more follow-up biopsies (P < 0.0005); (iii) were more likely to have positive cytology during follow-up (P < 0.005) and positive smears that were not followed within six months by a treatment with curative intent (P < 0.005); and (iv) experienced a higher risk of cancer of the cervix or vaginal vault (RR = 3.3 compared with the first period, 95% CI: 1.7-5.3). Among women diagnosed in 1965-1974, those initially managed by punch or wedge biopsy alone had a cancer risk ten times (95% CI: 3.9-25.7) higher than women initially treated with curative intent. CONCLUSIONS: During the 'clinical study' (1965-1974), women underwent numerous interventions that were aimed to observe rather than treat their condition, and their risk of cancer was substantially increased.

Utility of a mainstreamed genetic testing pathway in breast and ovarian cancer patients during the COVID-19 pandemic.

INTRODUCTION: Mainstreamed genetic testing (MGT) obviates the need for a cancer genetics consultation, since trained oncologists (O) and gynaecologists (G) provide counseling, prescribe testing and deliver results. We report results from our MGT program and emphasize its utility during the COVID-19 lockdown, when cancer genetics clinics had suspended their activity. METHODS: An MGT pathway for breast and ovarian cancer (BC/OC) patients was established in Jan-2018 between the Assistance Publique - Hôpitaux de Paris.Sorbonne Université Cancer Genetics team and the Oncology/Gynecology departments at one teaching and two regional hospitals. Trained O + G evaluated patients with the Manchester Scoring System. A 12-point threshold was recommended for testing. Next-generation sequencing of BRCA1, BRCA2, PALB2, RAD51C and RAD51D was performed. Results were delivered to the patient by O/G. Pathogenic variants (PV) carriers were referred to the genetics clinic. Results are reported for the 2nd-Jan-2018 to 1st-June-2020 period. That includes the eight-week COVID-19 lockdown and three-week de-confinement phase 1. RESULTS: Results were available for 231/234 patients. Twenty-eight (12.1%) carried a PV. Of the 27 patients tested during the COVID-19 period, three carried a PV, two in BRCA1 and one in RAD51C. The clinical impact was immediate for the two BRCA1 BC cases undergoing neo-adjuvant chemotherapy, since double mastectomy and salpingo-oophorectomy will now be performed using two-step strategies. CONCLUSIONS: MGT guaranteed care continuity in BC/OC patients during the critical phases of the COVID-19 pandemic, with immediate implications for PV carriers. More broadly, we report for the first time the successful implementation of MGT in France.

Male circumcision and serologically determined human papillomavirus infection in a birth cohort.

Circumcision has been reported to protect against infection with human papillomavirus (HPV) in men, but results have been inconsistent. We followed males in a birth cohort born in Dunedin, New Zealand, in 1972 and 1973 from age 3 to 32 years. Seropositivity at age 32 years for the oncogenic types HPV-16 and 18, and the nononcogenic types 6 and 11, was studied in relation to maternal reports of circumcision status at age 3 for 450 men. Seropositivity to any of these types was associated with lifetime number of sexual partners (P = 0.03), and lower moral-religious emphasis of the family of origin (P < 0.001). Circumcision was not found to be protective, with the adjusted odds ratio (95% confidence interval) for HPV6/11/16/18 seropositivity among the circumcised compared with the uncircumcised being 1.4 (0.89-2.2).

Longitudinal study of self-reported sexually transmitted infection incidence by gender and age up to age thirty-two years.

OBJECTIVES: To examine how incidence of self-reported sexually transmitted infections (STIs) varies by gender and age, and the factors that influence this. METHODS: A longitudinal study of a cohort born in Dunedin, New Zealand in 1972/1973. They were questioned about STIs and sexual behavior at age 21, 26, and 32 years (1993-2005). Incidence rates were calculated over 3 age periods and compared using Poisson regression. RESULTS: Of the 1037 members of the original cohort, 92% or more of survivors completed the computer questionnaire at each age. Incidence rates of STIs from first coitus to age 21, age 21 to 26, and age 26 to 32, were 2.0, 3.2, and 2.0 per 100 person-years, respectively for men and 4.4, 3.0, and 1.4 per 100 person-years, respectively for women. After adjustment for sexual behavior, rates for men were elevated from age 21 to 26 compared with first coitus to 21 years of age [incidence rate ratio (IRR) = 1.9, 95% confidence interval (CI) 1.3 to 2.8), but not from age 26 to 32 (IRR = 1.1, 95% CI 0.70-1.9). For women, adjusted rates decreased with age; from 21 to 26 compared with first coitus to 21 (IRR = 0.79, 95% CI 0.56-1.1) and further from 26 to 32 (IRR = 0.39, 95% CI 0.27-0.57). CONCLUSIONS: These unique data, comprising repeated assessment of reported behaviors and STIs in the same population, show that the period before age 21 is a time of special risk for STIs for women and of lower risk for men. The low risk among women aged 26 to 32 years after adjustment for sexual behavior warrants further investigation.

Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study.

BACKGROUND: The invasive potential of cervical intraepithelial neoplasia 3 (CIN3; also termed stage 0 carcinoma) has been poorly defined. At the National Women's Hospital, Auckland, New Zealand, treatment of CIN3 was withheld from a substantial number of women between 1965 and 1974 as part of an unethical clinical study. The resulting variation in management allows comparison of the long-term risk of invasive cancer of the cervix in women whose lesion was minimally disturbed with those who had adequate initial treatment followed by conventional management. We aimed to estimate the long-term risk of invasive cancer in these two groups of women. A judicial inquiry referred for independent clinical review in 1988 all women for whom there remained doubt about the adequacy of their management. METHODS: Between February, 2001, and December, 2004, medical records, cytology, and histopathology were reviewed for all women with CIN3 diagnosed between 1955 and 1976, whose treatment was reviewed by judicial inquiry and whose medical records could be located, and linkages were done with cancer and death registers and electoral rolls. To take into account the probability that the CIN3 lesion had been completely removed, we classified adequacy of treatment by type of procedure, presence of CIN3 at the excision margin, and subsequent cytology. The primary outcome was cumulative incidence of invasive cancer of the cervix or vaginal vault. Follow-up continued until death or Dec 31, 2000, whichever came first. Analyses accounted for procedures during follow-up. FINDINGS: 1229 women whose treatment was reviewed by the judicial inquiry in 1987-88 were included. Of these, 48 records (4%) could not be located and 47 women (4%) did not meet the inclusion criteria. At histopathological review, a further 71 (6% of 1134) women were excluded because the review diagnosis was not CIN3. We identified outcomes in the remaining 1063 (86% of 1229) women diagnosed with CIN3 at the hospital in 1955-76. In 143 women managed only by punch or wedge biopsy, cumulative incidence of invasive cancer of the cervix or vaginal vault was 31.3% (95% CI 22.7-42.3) at 30 years, and 50.3% (37.3-64.9) in the subset of 92 such women who had persistent disease within 24 months. However, cancer risk at 30 years was only 0.7% (0.3-1.9) in 593 women whose initial treatment was deemed adequate or probably adequate, and whose treatment for recurrent disease was conventional. INTERPRETATION: This study provides the most valid direct estimates yet available of the rate of progression from CIN3 to invasive cancer. Women with untreated CIN3 are at high risk of cervical cancer, whereas the risk is very low in women treated conventionally throughout.

Circumcision and risk of sexually transmitted infections in a birth cohort.

OBJECTIVE: To determine the impact of early childhood circumcision on sexually transmitted infection (STI) acquisition to age 32 years. STUDY DESIGN: The circumcision status of a cohort of children born in 1972 and 1973 in Dunedin, New Zealand was sought at age 3 years. Information about STIs was obtained at ages 21, 26, and 32 years. The incidence rates of STI acquisition were calculated, taking into account timing of first sex, and comparisons were made between the circumcised men and uncircumcised men. Adjustments were made for potential socioeconomic and sexual behavior confounding factors where appropriate. RESULTS: Of the 499 men studied, 201 (40.3%) had been circumcised by age 3 years. The circumcised and uncircumcised groups differed little in socioeconomic characteristics and sexual behavior. Overall, up to age 32 years, the incidence rates for all STIs were not statistically significantly different-23.4 and 24.4 per 1000 person-years for the uncircumcised and circumcised men, respectively. This was not affected by adjusting for any of the socioeconomic or sexual behavior characteristics. CONCLUSIONS: These findings are consistent with recent population-based cross-sectional studies in developed countries, which found that early childhood circumcision does not markedly reduce the risk of the common STIs in the general population in such countries.