Gerard Wain

Westmead Hospital, Sydney, New South Wales, Australia

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Publications (37)112.84 Total impact

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    ABSTRACT: Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. Experimental design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents.
    No preview · Article · Oct 2014 · Clinical Cancer Research
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    ABSTRACT: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.
    Full-text · Article · Jul 2013 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: Objectives To obtain health-related quality of life valuations (ie, utilities) for human papillomavirus (HPV)-related cancer health states of vulval, vaginal, penile, anal and oropharyngeal cancers for use in modelling cost-effectiveness of prophylactic HPV vaccination. Methods Written case descriptions of each HPV-associated cancer describing the ‘average’ patient surviving after the initial cancer diagnosis and treatment were developed in consultation with oncology clinicians. A general overview, standard gamble questionnaire for each health state and a quiz was conducted in 120 participants recruited from the general population. Results In the included population sample (n=99), the average age was 43 years (range = 18–70 years) with 54% men, 44% never married/43% married, 76% education beyond year 12 and 39% employed full-time. The utility values for the five health states were 0.57 (95% CI 0.52 to 0.62) for anal cancer, 0.58 (0.53 to 0.63) for oropharyngeal cancer, 0.59 (0.54 to 0.64) for vaginal cancer, 0.65 (0.60 to 0.70) for vulval cancer and 0.79 (0.74 to 0.84) for penile cancer. Participants demonstrated a very good understanding of the symptoms, diagnosis and treatment of these cancers with a mean score of 9 (SD=1.1) on a 10-item quiz. Conclusions This study provides utility estimates for the specific HPV-related cancers of vulval, vaginal, penile, anal and oropharyngeal cancers valued by a general population sample using standard gamble. The results demonstrate considerable quality of life impact associated with surviving these cancers that will be important to incorporate into modelling cost-effectiveness of prophylactic HPV vaccination in different populations.
    Full-text · Article · May 2012 · Sexually transmitted infections
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    J Perz · J M Ussher · P Butow · G Wain
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    ABSTRACT: PERZ J., USSHER J.M., BUTOW P. & WAIN G. (2011) European Journal of Cancer Care20, 610–619 Gender differences in cancer carer psychological distress: an analysis of moderators and mediators Women cancer carers report higher rates of distress than men; however, there is little understanding of the mechanisms underlying these gender differences. The aim of this study was to examine the potential mediating roles of burden of care, unmet needs, self-silencing, self-efficacy and optimism, and the potential moderating influence of social support, cancer stage, patient gender, time spent caring and other responsibilities, on gender differences in carer distress. Of 329 informal cancer carers (245 women, 119 men), women reported significantly more anxiety, burden of care and unmet needs than men. In the mediation analysis, gender differences in anxiety were fully explained by both the independent contribution and combination of: Disrupted Schedule, Health Problems and Emotional and Spiritual Unmet Needs. Women cared for both men and women patients, across a broad range of relationships, whereas men predominantly cared for their female partner. There was no gender difference in number of hours spent caring or in companionship, amount of support received, and additional responsibilities for children, housework or studies, and none of these factors acted as moderators of gender differences in anxiety. It is concluded that women's gendered role is associated with unmet needs and burden of care, resulting in greater anxiety.
    Full-text · Article · May 2011 · European Journal of Cancer Care
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    ABSTRACT: Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute to the development of ovarian cancer.
    Full-text · Article · Mar 2011 · PLoS ONE
  • Gerard Wain
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    ABSTRACT: Australia was the first country in the world to introduce a governmentfunded, population-based mass vaccination program against HPV, using the quadrivalent vaccine. The program has been very successful in terms of high coverage and participation, community awareness and acceptance. The health outcomes and cost-effectiveness associated with the quadrivalent vaccine make a strong case for maintaining the quadrivalent vaccine as the vaccine of choice for this program.
    No preview · Article · Sep 2010 · Sexual Health
  • Gerard Wain
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    ABSTRACT: Prophylactic HPV vaccines have demonstrated high efficacy against a range of HPV related diseases. They have been widely adopted as population health interventions in many jurisdictions and their routine use has been endorsed by the WHO. The development of these vaccines comes after an increased understanding of the natural history and epidemiology of HPV infection and disease in both males and females. Persistent HPV infection with oncogenic types induces malignant transformation in a range of epithelia including the cervix, anogenital regions, the penis and a number of head and neck sites. In relation to HPV disease prevention in the post-reproductive years, most infections occur soon after commencement of sexual activity but new infections do occur throughout the age spectrum. This reduces the likely impact of prophylactic vaccines in this population. The major impact on HPV related disease in this age group will come from advances in screening and early detection of HPV and neoplastic precursors. The most appropriate prevention for any individual man or women in this age group will be an individualised combination of vaccination, screening and early detection depending on the individual's own circumstances.
    No preview · Article · Mar 2010 · Maturitas
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    ABSTRACT: To evaluate the outcome in patients with uterine papillary serous carcinoma (UPSC). A retrospective review of women treated for UPSC between 1995 and 2006 in Westmead Hospital, Sydney. The patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy and surgical staging. The majority of the patients had platinum-based adjuvant chemotherapy and radiotherapy. Sites of initial recurrence were documented. Overall survival (OS) and progression free survival (PFS) were estimated using Kaplan-Meier method. Univariate and multivariate analysis was performed using Cox regression analysis to test the effects of multiple prognostic factors on survival. Two-year and five-year OS was 65% and 43%. The median OS was 39 months. Two-year and five-year PFS was 60% and 35%. Macroscopic residual disease at the completion of surgery was the only significant prognostic factor associated with worse OS on both univariate and multivariate analysis (P < 0.001). The median OS was only 11 months if patients had macroscopic residual disease, and all patients died within 18 months despite adjuvant therapies. Twenty-one patients relapsed. The site(s) of initial recurrence were: vagina (five patients), pelvic lymph nodes (four patients), abdomen (11 patients), para-aortic lymph nodes (six patients), inguinal lymph nodes (two patients) and distant metastases in seven patients. Only one of 16 patients who received vaginal brachytherapy failed in the vagina, but three of seven patients who received external beam pelvic radiotherapy failed in the vagina. We recommend optimal cytoreduction surgery with the aim of leaving no macroscopic disease at the end of the operation. Vaginal brachytherapy should be considered as a component of adjuvant radiotherapy. Abdominal failure was the commonest mode of failure in our cohort of patients.
    Full-text · Article · Aug 2009 · Australian and New Zealand Journal of Obstetrics and Gynaecology
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    ABSTRACT: The standard of care for ovarian cancer includes platinum-based chemotherapy. It is not possible, however, to predict clinical platinum sensitivity or to design rational strategies to overcome resistance. We used a novel approach to identify altered gene expression associated with high sensitivity to cisplatin, to define novel targets to sensitize tumor cells to platins and ultimately improve the effectiveness of this widely used class of chemotherapeutics. Using differential display PCR, we identified genes differentially expressed in a mutagenized cell line with unusual sensitivity to cisplatin. The most highly differentially expressed gene was selected, and its role in determining cisplatin sensitivity was validated by gene transfection and small interfering RNA (siRNA) approaches, by association of expression levels with cisplatin sensitivity in cell lines, and by association of tumor expression levels with survival in a retrospective cohort of 71 patients with serous ovarian adenocarcinoma. The most highly differently expressed gene identified was ANKRD1, ankyrin repeat domain 1 (cardiac muscle). ANKRD1 mRNA levels were correlated with platinum sensitivity in cell lines, and most significantly, decreasing ANKRD1 using siRNA increased cisplatin sensitivity >2-fold. ANKRD1 was expressed in the majority of ovarian adenocarcinomas tested (62/71, 87%), and higher tumor levels of ANKRD1 were found in patients with worse outcome (overall survival, P=0.013). These findings suggest that ANKRD1, a gene not previously associated with ovarian cancer or with response to chemotherapy, is associated with treatment outcome, and decreasing ANKRD1 expression, or function, is a potential strategy to sensitize tumors to platinum-based drugs.
    Preview · Article · Nov 2008 · Clinical Cancer Research
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    Gerard V Wain
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    ABSTRACT: Cervical cancer prevention relies on two different age-specific technologies, and consumers should not be misled about the role of HPV vaccines.
    Preview · Article · Jun 2008 · The Medical journal of Australia
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    ABSTRACT: To explore views on the ideal structure and process of support groups for cancer patients. From 184 cancer support groups identified in NSW, Australia, 50 were randomly selected within strata of five variations in group structure: homogenous versus heterogenous participants; urban versus rural; community versus hospital setting, leader with cancer experience or not; and with professional training or not. Four hundred and seventy-six group members completed a questionnaire. Participants valued being with others like them, gaining information about cancer and having an effective leader. Groups were seen to be currently failing people from culturally and linguistically diverse backgrounds, and links with oncology health professionals were inadequate. Few clear preferences for structure were expressed, except for the non-exclusion of those with a poor prognosis. Patients tended to prefer the structure of their own group, but patients longer since diagnosis, those with better informal support and carers preferred to meet in the community setting, while men with prostate cancer preferred a medical setting. Some suggestions for group structure and process can be made on the basis of these findings; however, individual variation suggests that a needs analysis should be made by individual groups.
    No preview · Article · Nov 2007 · Psycho-Oncology
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    ABSTRACT: The cost-effectiveness of adding a human papillomavirus (HPV) vaccine to the Australian National Cervical Screening Program compared to screening alone was examined. A Markov model of the natural history of HPV infection that incorporates screening and vaccination was developed. A vaccine that prevents 100% of HPV 16/18-associated disease, with a lifetime duration of efficacy and 80% coverage offered through a school program to girls aged 12 years, in conjunction with current screening was compared with screening alone using cost (in Australian dollars) per life-year (LY) saved and quality-adjusted life-year (QALY) saved. Sensitivity analyses included determining the cost-effectiveness of offering a catch-up vaccination program to 14-26-year-olds and accounting for the benefits of herd immunity. Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of $51 103 per LY and $18 735 per QALY, assuming a cost per vaccine dose of $115. Results were sensitive to assumptions about the duration of vaccine efficacy, including the need for a booster ($68 158 per LY and $24 988 per QALY) to produce lifetime immunity. Accounting for herd immunity resulted in a more attractive ICER ($36 343 per LY and $13 316 per QALY) for girls only. The cost per LY of vaccinating boys and girls was $92 052 and the cost per QALY was $33 644. The cost per LY of implementing a catch-up vaccination program ranged from $45 652 ($16 727 per QALY) for extending vaccination to 14-year-olds to $78 702 ($34 536 per QALY) for 26-year-olds. These results suggest that adding an HPV vaccine to Australia's current screening regimen is a potentially cost-effective way to reduce cervical cancer and the clinical interventions that are currently associated with its prevention via screening alone.
    No preview · Article · Oct 2007 · Sexual Health
  • K Hodgkinson · P Butow · K M Hobbs · G E Hunt · S K Lo · G Wain
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    ABSTRACT: Partners of cancer patients typically provide the majority of patients' emotional and physical care. Partners may be profoundly affected by the cancer and may experience ongoing supportive care needs across the survivorship continuum. Research has been restricted by a lack of psychometrically evaluated measures and in this study, a self-report measure of partners' needs was developed and empirically evaluated. Questionnaire items generated from a qualitative study were constructed into a 47- item unmet need measure (Cancer Survivors' Partners Unmet Needs measure, CaSPUN). The psychometric properties of the CaSPUN were evaluated in 212 partners of patients who had been diagnosed with cancer 1-11 years earlier and were currently disease-free. The CaSPUN was modified to include 35 unmet need items, 6 positive change items and an open ended item. The CaSPUN demonstrates a high level of acceptability, internal consistency and construct validity, although test-retest reliability was moderate. Factor analysis identified five discrete factors: (1) Relationships, (2) Information, (3) Partner Issues, (4) Comprehensive Care and (5) Emotional Support. The CaSPUN permits the identification of long-term supportive care needs in generic populations of cancer survivors' partners and will assist with the formulation of recommendations regarding required supportive care services.
    No preview · Article · Sep 2007 · Psycho-Oncology
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    ABSTRACT: Many cancer survivors experience ongoing morbidity over the survivorship continuum and their supportive care needs have yet to be comprehensively assessed. This study aimed to develop and empirically evaluate a self-report measure of cancer survivors' supportive care needs. In Phase I, questionnaire items were generated based upon previous qualitative research that identified both unique and shared needs in survivors and their partners; items were constructed into the Cancer Survivors' Unmet Needs measure (CaSUN). In Phase 2, the CaSUN was completed by 353 cancer survivors who had been diagnosed with cancer between 1 and 15 years earlier and were currently disease-free. After modification, the CaSUN included 35 unmet need items, 6 positive change items and an open-ended question. Good acceptability, internal consistency and validity were demonstrated, although test-retest reliability was low. Maximum likelihood factor analysis identified five discrete factors: Existential Survivorship, Comprehensive Care, Information, Quality of Life and Relationships. Preliminary data indicates that the CaSUN meets the majority of psychometric criteria for assessment measures, although its low test-retest reliability awaits further investigation. The CaSUN will facilitate the evaluation of supportive care services and generation of service delivery recommendations for cancer survivors.
    No preview · Article · Sep 2007 · Psycho-Oncology
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    ABSTRACT: A significant proportion of breast cancer patients experience psychosocial morbidity after treatment, although their longer-term outcomes and supportive care service needs have not been comprehensively documented. The aim of this study was to identify longer-term outcomes and supportive care needs in disease-free breast cancer survivors. One hundred seventeen patients who had been diagnosed with breast cancer 2-10 years earlier completed questionnaires to assess psychosocial outcomes including supportive care needs, psychological distress, and quality of life (QoL). QoL and depression scores were consistent with community rates although anxiety scores were higher. Approximately two thirds of survivors reported at least one unmet need, most frequently concerning existential survivorship issues, thereby highlighting the unique needs of survivors. Years since diagnosis was not correlated with need levels. Survivors classified as clinically anxious reported over three times as many unmet needs and survivors classified as depressed reported over two and a half times as many unmet needs. Positive outcomes were frequently reported. The findings have direct clinical relevance: irrespective of years since diagnosis, comprehensive and extended supportive care services are required to identify breast cancer survivors in need of supportive care interventions and remediate high levels of anxiety.
    No preview · Article · Jun 2007 · Supportive Care Cancer
  • K Hodgkinson · P Butow · G E Hunt · R Wyse · K M Hobbs · G Wain
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    ABSTRACT: Partners of cancer patients may experience significant distress at the time of treatment and many may experience persistent difficulties, although little research has examined their longer term psychosocial outcomes or supportive care needs. One hundred and fifty-four cancer survivors who were 1-11 years post diagnosis and disease-free and their partners completed mailed questionnaires. A positive relationship was found between psychological distress and supportive care needs both within and between partner and survivor samples. Partners reported high levels of anxiety and supportive care needs, most frequently concerning relationships and the impact of the cancer illness. Partners within couples reported both shared and unique needs, although agreement on ratings of shared needs was low. Needs did not diminish over time although partners demonstrated psychological resilience and reported positive outcomes. Predictors of distress and unmet needs were explored: physical QOL, relationship satisfaction, and total needs contributed to variability in partners' distress; relationship satisfaction and total needs were associated with survivors' distress. Distress and relationship satisfaction were associated with partners' unmet needs; only distress was associated with survivors' unmet needs. Partners are not merely providers of support, but need support themselves many years after a cancer diagnosis and in the context of apparently cured disease. The quality of the dyadic relationship may be critical in determining both partner and survivor distress and needs, and may prove a useful target for psychosocial interventions.
    No preview · Article · May 2007 · Supportive Care Cancer
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    ABSTRACT: To assess the long-term psychosocial outcomes and supportive care needs of gynecologic cancer survivors. Women who had received care in a tertiary-based gynecologic cancer center 1-8 years earlier and who were disease-free were invited to complete a mailed self-report questionnaire to assess psychosocial outcomes and supportive care needs. In total, 199 survivors participated in the study. Survivors reported normal quality of life and relationship adjustment although functioning was at the lower end of the range; over two-thirds (68%) reported positive outcomes. However, nearly one-third (29%) reported clinical levels of anxiety and the most frequently endorsed need concerned fear of disease recurrence (24%). About one-fifth (19%) reported symptoms that indicated posttraumatic stress disorder (PTSD) and this rose to close to one-third (29%) for survivors of advanced stage disease. Nearly 90% of survivors reported supportive care needs and the diagnosis of anxiety or PTSD resulted in a four-fold increase in unmet needs. Needs most frequently concerned "existential survivorship" (e.g., spiritual beliefs, decision making, the meaning of life) and "comprehensive cancer care" (e.g., team care, communication, local health care services). Years since diagnosis was not related to distress or need levels. All members of the care team need to be aware that significant psychosocial morbidity may occur many years after the successful treatment of a gynecologic malignancy and may be associated with elevated supportive care needs. Comprehensive and extended supportive care services are required to address anxiety and trauma responses and investigate strategies to meet ongoing needs in order to improve long-term psychosocial outcomes.
    No preview · Article · Mar 2007 · Gynecologic Oncology
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    ABSTRACT: Cancer patients and their partners experience elevated distress and unmet supportive care needs at the time of treatment, however, their ongoing needs have not been adequately described. This qualitative study explores the needs of disease-free cancer survivors and their partners using semi-structured telephone interviews. A convenience sample of 25 key informants' identified needs in the domains of information, health care, physical functioning, relationships, emotions, socio-economic issues, expectations and life perspective; and the positive outcomes are widely reported. The identification of unique needs of survivors and partners supports the development of supportive care measures to specifically assess ongoing care need in these populations.
    No preview · Article · Feb 2007 · Journal of Psychosocial Oncology
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    Gerard V Wain

    Preview · Article · Dec 2006 · The Medical journal of Australia
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    ABSTRACT: To examine time trends in cervical cancer incidence and mortality in NSW women aged yen20 years in relation to important health service initiatives and programs. Data on cervical cancer incidence and mortality were obtained from the NSW Central Cancer Registry for 1972-2001, and corresponding annual populations obtained from the Australian Bureau of Statistics. Direct age-standardised rates in the yen20 year population were calculated using the 2001 NSW census population as standard. Proportional reductions in incidence and mortality since 1972-1974 were also calculated and related to key health service factors and to published NSW 5-year cervical cancer relative survival for similar periods. Declines in cervical cancer incidence (-10%) and mortality (-20%), and increased degree-of-spread specific survival following the introduction of universal health care in 1975 suggest effects of greater access to Pap screening, earlier access to diagnosis and treatment services, and improved effectiveness of treatment. Incidence plateaued during the 1980s, but mortality fell further (-7%) due to an increased proportion of localised cancers (without change to degree-of-spread specific survival). The 1980s mortality reduction was a consequence of earlier diagnosis and/or secondary prevention, not improved treatment effectiveness or reduced incidence. A marked and sustained incidence decline to 2001 (-35%) occurred after the introduction of the NSW Cervical Screening Program in 1992. This was followed 3 years later by a sustained mortality decline (-20%). During the 1990s survival across all degrees of spread remained unchanged and the mortality reduction was due entirely to reduction in incidence. The substantial reduction of cervical cancer incidence and mortality in NSW over the last 3 decades is associated with important health service interventions that relate to control of cervical cancer, particularly the implementation of a population-based organised cervical screening program.
    No preview · Article · May 2006 · Cancer Causes and Control

Publication Stats

1k Citations
112.84 Total Impact Points

Institutions

  • 1996-2014
    • Westmead Hospital
      • Westmead Centre for Gynecological Cancer
      Sydney, New South Wales, Australia
  • 2003-2005
    • University of Sydney
      • Discipline in Obstetrics and Gynaecology
      Sydney, New South Wales, Australia