ABSTRACT
Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1-6 CpG-sites), hTERT (1-10 CpG-sites) and FAM19A4 (1-5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.
ABSTRACT
CONTEXT.: Detection of human papillomavirus (HPV) in formalin-fixed, paraffin-embedded (FFPE) tissues may identify the cause of lesions and has value for the development of new diagnostic assays and epidemiologic studies. Seegene Anyplex II assays are widely used for HPV screening, but their performance using FFPE samples has not been fully explored. OBJECTIVE.: To validate Anyplex II HPV HR Detection (Anyplex II, Seegene) using FFPE samples. DESIGN.: We used 248 stored DNA extracts from cervical cancer FFPE samples collected during 2005-2015 that tested HPV positive using the RHA kit HPV SPF10-LiPA25, v1 (SPF10, Labo Biomedical Products) HPV genotyping assay, manufacturer-validated for FFPE samples. RESULTS.: Of the selected 248 samples, 243 were used in our analysis. Consistent with SPF10 genotyping results, Anyplex II detected all 12 oncogenic types and had an overall HPV detection rate of 86.4% (210 of 243 samples). Anyplex II and SPF10 showed very high agreement for the detection of the 2 most important oncogenic genotypes: HPV 16 (219 of 226; 96.9%; 95% CI, 93.7-98.75) and HPV 18 (221 of 226; 97.8%; 95% CI, 94.9-99.3). CONCLUSIONS.: Overall results showed that both platforms produced comparable HPV genotyping results, indicating the suitability of Anyplex II for FFPE samples. The Anyplex II assay has the added convenience of being an efficient, single-well semiquantitative polymerase chain reaction assay. Further optimization of Anyplex II may enhance its performance using FFPE samples by improving the detection limit.
Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Human Papillomavirus Viruses , Papillomavirus Infections/diagnosis , Paraffin Embedding/methods , Papillomaviridae/genetics , Genotype , DNA, Viral/genetics , DNA, Viral/analysis , FormaldehydeABSTRACT
BACKGROUND: The transition of Australia's National Cervical Screening Program from cytology to a molecular test for human papillomavirus (HPV) (locally referred to as the 'Renewal'), including a longer five-year interval and older age at commencement, significantly impacted all sectors of program delivery. The Renewal had major implications for the roles and requirements of pathology laboratories providing services for the Program. This study aimed to understand the early impacts of the Renewal and its implementation on the pathology sector. METHODS: Semi-structured qualitative interviews were conducted with key stakeholders (N = 49) involved in the STakeholder Opinions of Renewal Implementation and Experiences Study (STORIES), 11-20 months after the program transition. A subset of interviews (N = 24) that discussed the pathology sector were analysed using inductive thematic analysis. RESULTS: Four overarching themes were identified: implementation enablers, challenges, missed opportunities, and possible improvements. Participants believed that the decision to transition to primary HPV screening was highly acceptable and evidence-based, but faced challenges due to impacts on laboratory infrastructure, resources, staffing, and finances. These challenges were compounded by unfamiliarity with new information technology (IT) systems and the new National Cancer Screening Register ('Register') not being fully functional by the date of the program transition. The limited availability of self-collection and lack of standardised fields in pathology forms were identified as missed opportunities to improve equity in the Program. To improve implementation processes, participants suggested increased pathology sector involvement in planning was needed, along with more timely and transparent communication from the Government, and clearer clinical management guidelines. CONCLUSION: The transition to primary HPV screening had a significant and multifaceted impact on the Australian pathology sector reflecting the magnitude and complexity of the Renewal. Strategies to support the pathology sector through effective change management, clear, timely, and transparent communication, as well as adequate funding sources will be critical for other countries planning to transition cervical screening programs.
Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Early Detection of Cancer , Papillomavirus Infections/diagnosis , Papillomavirus Infections/prevention & control , Australia , Mass ScreeningABSTRACT
Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced in 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2013-2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were 1.67% (95%CI:1.21-2.13%) by LA, 1.49% (95%CI:1.05-1.93%) by cobas, and 1.63% (95%CI:1.17-2.08%) for cobas and LA testing of non-16/18 cobas positives (cobas/LA). Age-standardised pre-vaccination oncogenic HPV prevalence was 15.70% (95%CI:13.79-17.60%) by LA; post-vaccination estimates were 9.06% (95%CI:8.02-10.09%) by LA, 8.47% (95%CI:7.47-9.47%) by cobas and cobas/LA. Standardised rate ratios between post-vs. pre-vaccination rates were significantly different for HPV16/18, non-16/18 HPV and oncogenic HPV: 0.34 (95%CI:0.23-0.50), 0.68 (95%CI:0.55-0.84) and 0.58 (95%CI:0.48-0.69), respectively. Additional strategies (LA for all cobas positives; combined cobas and LA results on all samples) had similar results. If a single method is applied consistently, it will provide important data on relative changes in HPV prevalence following vaccination.
Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Adult , Middle Aged , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Human papillomavirus 16 , Papillomavirus Infections/diagnosis , Early Detection of Cancer/methods , Human papillomavirus 18/genetics , Population SurveillanceABSTRACT
Abstract: The Australian Paediatric Surveillance Unit (APSU) has been conducting surveillance of rare communicable and non-communicable conditions in children since its inception in 1993. In this report, the results are described of surveillance of ten communicable diseases (and complications) for 2021, including the numbers of cases and incidence estimates; demographics; clinical features; and management and short-term outcomes. The included diseases are: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV); neonatal herpes simplex virus (HSV) infection; paediatric human immunodeficiency virus (HIV) infection; perinatal exposure to HIV; severe complications from influenza; juvenile-onset respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. In 2021, cases of JoRRP were reported to the APSU for the first time since 2017, indicating potential gaps in HPV vaccination. AFP surveillance by APSU again contributed to Australia achieving a minimum target incidence of one AFP case per 100,000 children aged < 15 years. There were no cases of children with severe complications of influenza. No cases of varicella or congenital rubella were reported; however, at-risk populations, especially young migrant and refugee women from countries without universal vaccination programs, need to be screened and prioritised for vaccination prior to pregnancy. Cases of perinatal exposure to HIV continue to increase; however, the rate of mother-to-child-transmission remains at low levels due to the use of effective intervention strategies. Case numbers of congenital CMV and neonatal HSV remain steady in the absence of vaccines, prompting the need for greater awareness and education, with recent calls for target screening of at-risk infants for congenital CMV.
Subject(s)
Chickenpox , Communicable Diseases , Cytomegalovirus Infections , HIV Infections , Influenza, Human , Rubella Syndrome, Congenital , Female , Humans , Infant , Infant, Newborn , Pregnancy , Australia/epidemiology , Chickenpox/epidemiology , Chickenpox/prevention & control , Communicable Diseases/epidemiology , HIV Infections/epidemiology , Infectious Disease Transmission, Vertical , Influenza, Human/epidemiologyABSTRACT
OBJECTIVES: Previously, based on 6 months of follow-up, we showed that HPV self-sampling improved participation in cervical screening compared to a reminder letter for Pap testing for never- and under-screened women. Here, we report follow-up and related screening outcomes for women who participated in the initial self-sampling over two screening rounds. SETTING: The randomised controlled trial was conducted in Australia. METHODS: Never- and under-screened women were randomly allocated to the HPV self-sampling or the reminder for Pap test arm and followed at 6 and 36 months since the kits were first mailed. RESULTS: The first round of HPV self-sampling kits were mailed from May-July 2014 to 12 572 women. After 36 months, 19% of never-screened and 9% of under-screened women returned a kit for HPV testing; 2.7% were HPV 16/18 and 5.8% non-16/18 HPV positive. Compliance with first round follow-up was 84% (95% CI: 77.1-89.5%). Non-compliant and cytology triage negative women were mailed another kit at 12 months. Compliance at 12-month follow-up was 59.3% (49.4 to 68.6%). Of 37 women with a 12-month repeat HPV, 70% were positive. Of women who tested negative for HPV in the first round (n = 1573), 25% attended regular screening in the next round and none had CIN2 + detected. The overall prevalence of CIN2 + was 8.5 per 1000 screened (4.8 to 13.9 per 1000). CONCLUSION: While self-sampling can successfully engage women, compliance with repeat testing may require monitoring. The clinician-supported self-collection pathway now in use in Australia will likely improve women's engagement with follow-up.
Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Australia/epidemiology , Early Detection of Cancer , Female , Follow-Up Studies , Human papillomavirus 16 , Human papillomavirus 18 , Humans , Mass Screening , Papillomaviridae , Papillomavirus Infections/epidemiology , Self Care , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Vaginal SmearsABSTRACT
BACKGROUND: Australia has had significant successes in the prevention of cervical cancer. However, there is considerable scope for improving screening participation. In December 2017, Australia shifted from cytology to a human papillomavirus-based screening program as part of the renewed National Cervical Screening Program. This provided the opportunity to introduce a clinician-supported self-collection cervical screening pathway, which allows screening participants aged 30 years or more and who are under-screened or never-screened to screen via a self-collected human papillomavirus test. OBJECTIVE: This study aimed to explore screening participant experiences of a clinician-supported self-collection cervical screening pathway. METHODS: Interviews (n = 45) were conducted with participants who had used the clinician-supported self-collection cervical screening pathway in the Australian National Cervical Screening Program between December 2017 and April 2019. Interviews were analyzed using template analysis. RESULTS: Under-screened and never-screened participants reported a variety of interrelated barriers to cervical screening due to the nature of the test. For these participants, self-collection was a preferable way to perform screening as it overcame various barriers, was easy to use and promoted a sense of empowerment. Participants reported that the role of their practitioner was influential in their decision to undertake cervical screening, and that the support and information provided was a key factor in their experiences of the self-collection pathway. CONCLUSION: Findings support the use of a clinician-supported model of care, as an alternative screening modality in Australia's National Cervical Screening Program. As more countries consider the move from a cytology to human papillomavirus-based cervical screening program, this model may assist in greater engagement of under-screened participants.
Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Adult , Australia , Early Detection of Cancer , Female , Humans , Mass Screening , Papillomaviridae , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms/prevention & controlSubject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Early Detection of Cancer , Female , Humans , Mass Screening , Papillomaviridae , Papillomavirus Infections/diagnosis , Self Care , Specimen Handling , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Vaginal SmearsABSTRACT
OBJECTIVES: To evaluate the implementation and acceptability of the self-collection cervical screening pathway since commencement of the renewed National Cervical Screening Program (rNCSP), from the perspectives of screening participants and primary care practitioners. DESIGN, SETTING, PARTICIPANTS: Qualitative study; individual semi-structured interviews with 45 screening participants and 18 primary care practitioners in Victoria who had engaged with the self-collection pathway during the first 17 months of the rNCSP (1 December 2017 - 30 April 2019). RESULTS: The self-collection pathway was highly acceptable as an alternative cervical screening pathway for most participating screening participants and practitioners. Some screening participants indicated that they would not have been screened had the pathway not been available. Acceptability was lower among those who had tested positive for HPV types not 16/18, a result that requires additional testing of a clinician-collected cervical sample. Use of the self-collection pathway is driven more by practitioners than their patients. Interpretations of the self-collection guidelines varied between practices. Barriers to expanding promotion of the pathway by practitioners included difficulties with identifying eligible participants. CONCLUSIONS: Increasing the accessibility of the self-collection pathway to under- and never screened women could reduce inequities in cervical cancer outcomes for those not participating in the main screening pathway. Practitioners should be provided resources to integrate self-collection into routine practice and to efficiently implement the entire self-collection pathway, in order to maximise its use and to optimise the experience for screening participants.
Subject(s)
Early Detection of Cancer/methods , Self-Testing , Uterine Cervical Neoplasms/diagnosis , Adult , Australia , Female , Humans , Qualitative ResearchABSTRACT
BACKGROUND: Initially, three-dose schedules were recommended for vaccines against human papillomavirus (HPV); subsequently recommendations have been updated to a schedule of two doses delivered at least six (minimum five) months apart for those aged <15 years at dose 1. We aimed to re-estimate effective HPV vaccination coverage in Australia, considering reduced-dose schedules and possible one-dose effectiveness. We also aimed to identify which of the three school visits was most commonly missed amongst two-dose only recipients, to inform optimal timing of visits. METHODS: National vaccination register data were used to estimate: i) vaccination coverage at December 2017, either with a complete course (three or two sufficiently-spaced doses (>151 days apart)), or at least one dose; ii) for each birth cohort offered vaccination, the percentage of the initially targeted cohort with a complete course, or at least one dose (reflecting uptake at the time the vaccine was offered); and iii) among two-dose only recipients, the percentage who missed each of three school visits. RESULTS: Including those with two sufficiently-spaced doses increased end-2017 coverage by 1.3-2.8% points in those vaccinated at school. Including those with at least one dose increased coverage further, by 6.5-9.5% points, mostly due to including those receiving multiple too-closely-spaced doses. One-dose coverage reached 90.9% and 86.9% in females and males respectively born in 2002. Among those vaccinated at school who received only two doses, it was much more common to miss the first (31.0% females; 32.5% males) or the third visit in the school year (54.6% females; 48.6% males) than the second (14.1% females; 18.8% males). CONCLUSIONS: Including those with two sufficiently-spaced doses has a very modest impact on HPV vaccine coverage in Australia. If receiving at least one dose offers substantial protection, these data suggest that the school-based program is now achieving close to 90% coverage on this measure.
Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Adult , Australia , Female , Humans , Male , Papillomavirus Infections/prevention & control , Vaccination , Vaccination Coverage , Young AdultSubject(s)
Multiple Sclerosis/complications , Opportunistic Infections/prevention & control , Practice Guidelines as Topic , Pregnancy Complications/prevention & control , Vaccination/standards , Australia , Female , Humans , Immunocompromised Host , Immunogenicity, Vaccine , Immunologic Factors/adverse effects , Male , Multiple Sclerosis/blood , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Opportunistic Infections/complications , Opportunistic Infections/immunology , Opportunistic Infections/microbiology , Pregnancy , Pregnancy Complications/immunology , Pregnancy Complications/microbiology , Seroconversion , Vaccination/adverse effects , Vaccines/administration & dosage , Vaccines/adverse effects , Vaccines/immunologyABSTRACT
The Australian Paediatric Surveillance Unit (APSU) has been prospectively collecting national data on rare childhood conditions since 1993, with monthly reporting of cases by paediatricians. In this report we describe annual results from studies for ten communicable diseases and complications of communicable diseases that were conducted using APSU surveillance in 2019 and place these in an historic context. Results are reported on acute flaccid paralysis, congenital cytomegalovirus infection, neonatal herpes simplex virus infection, perinatal exposure to HIV, paediatric HIV infection, severe complications of seasonal influenza, juvenile onset recurrent respiratory papillomatosis (JoRRP), congenital rubella syndrome, congenital varicella syndrome and neonatal varicella infection. APSU provides rich clinical data to complement data collected from other surveillance systems and to improve understanding and response to rare childhood infections.
Subject(s)
Communicable Diseases/epidemiology , Public Health Surveillance , Adolescent , Australia/epidemiology , Chickenpox/epidemiology , Child , Child, Preschool , Communicable Diseases/history , Congenital Abnormalities/epidemiology , Cytomegalovirus Infections/epidemiology , Female , HIV Infections/epidemiology , Herpes Simplex/epidemiology , History, 21st Century , Humans , Incidence , Infant , Infant, Newborn , Papillomavirus Infections/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Rare Diseases/epidemiology , Respiratory Tract Infections/epidemiology , Rubella Syndrome, Congenital/epidemiologySubject(s)
Mass Screening/statistics & numerical data , Medical Record Linkage , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Adult , Australia , Female , Humans , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines , Quality Assurance, Health Care , Uterine Cervical Neoplasms/virology , Vaginal Smears , Young AdultSubject(s)
Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Papillomavirus Vaccines/immunology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Australia/epidemiology , False Negative Reactions , Female , Humans , Papanicolaou Test , Papillomaviridae/genetics , Uterine Cervical Neoplasms/epidemiology , Vaccination , Vaginal SmearsSubject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Follow-Up Studies , Humans , Immunization Schedule , VaccinationABSTRACT
AIM: Prophylactic human papillomavirus (HPV) vaccines are highly effective at preventing pre-cancerous cervical lesions when given in a three-dose schedule. Some post-hoc trial data suggest that one dose prevents HPV infection. If one dose could prevent pre-cancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated. We assessed the effectiveness of quadrivalent HPV vaccine by number of doses against cervical intraepithelial neoplasia (CIN) 2 or 3/adenocarcinoma-in-situ (AIS)/cancer in Australia up to seven years post vaccination. METHODS: We linked registry data from all 8 jurisdictional cervical screening registers, with the national HPV vaccination register, death index and cancer registers for all Australian women aged 15 or under when eligible for vaccine who screened between April 2007 (when vaccination commenced) and 31 December 2014. We performed Cox proportional hazard regression, adjusted a priori for age, socioeconomic status, and area of residence, to estimate hazard ratios of histologically confirmed CIN2/CIN3/AIS/cancer. RESULTS: We included 250,648 women: 48,845 (19·5%) unvaccinated, 174,995 (69·8%) had received three doses, 18,190 (7·3%) two doses and 8,618 (3·4%) one dose. The adjusted hazard ratio was significantly lower for all dose groups compared to unvaccinated women (1 dose 0·65 (95%CI 0·52-0·81), 2 doses 0·61 (0·52-0·72) and 3 doses 0·59 (0·54-0·65).) With adjustment for age at vaccination amongst the vaccinated group, the adjusted hazard ratios for one dose and two dose recipients were comparable to three dose recipients (one dose 1.01 (95%CI 0.81-1.26), two doses 1.00 (0.85-1.17).) Multiple sensitivity analyses, including use of different dose assignment methods, produced consistent findings. Comparison with a historical cohort of age matched women showed that the result was not due to herd protection alone. CONCLUSIONS: One dose had comparable effectiveness as two or three doses in preventing high-grade disease in a high coverage setting. These findings support the hypothesis that one dose vaccination may be a viable strategy when working towards the global elimination of cervical cancer.
Subject(s)
Alphapapillomavirus/immunology , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/immunology , Adolescent , Adult , Australia/epidemiology , Female , Humans , Middle Aged , Outcome Assessment, Health Care , Proportional Hazards Models , Public Health Surveillance , Vaccination , Young Adult , Uterine Cervical Dysplasia/etiology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/prevention & controlABSTRACT
OBJECTIVE: To estimate human papillomavirus (HPV) vaccination coverage and course completion rates for Indigenous adolescents in four Australian states and territories. PARTICIPANTS, SETTING: Adolescents who were 12 years old in 2015 and received the quadrivalent HPV vaccine (three doses: 0, 2, 6 months) as part of the National HPV Vaccination Program in 2015 or 2016 in New South Wales, Queensland, the Northern Territory, or the Australian Capital Territory. MAIN OUTCOME MEASURES: Estimated HPV vaccination coverage by dose and by Indigenous status and sex, based on National HPV Vaccination Program Register data; vaccination course completion rates (proportion of dose 1 recipients who received dose 3) for 12-year-olds vaccinated during 2013-2016, by sex, jurisdiction, and Indigenous status. RESULTS: Dose 1 coverage exceeded 80% for all Indigenous status/jurisdiction/sex groups (range, 83.3-97.7%). Coverage was similar for Indigenous and non-Indigenous girls in Queensland (87.3% v 87.0%), lower for Indigenous girls in the ACT (88.7% v 97.7%) and the NT (91.1% v 97.0%), and higher in NSW (95.9% v 89.9%); it was similar for Indigenous and non-Indigenous boys in all jurisdictions except the NT (88.6% v 96.3%). Dose 3 coverage (range, 61.2-87.7%) was markedly lower for Indigenous than non-Indigenous 12-year-olds in all jurisdictions, except for girls in NSW (82.6% v 83.6%). CONCLUSION: HPV vaccine coverage is high, but course completion is generally lower for Indigenous adolescents. Strategies for improving completion rates for Indigenous Australians are needed to end the higher burden of cervical cancer among Indigenous than non-Indigenous women.
Subject(s)
Native Hawaiian or Other Pacific Islander/statistics & numerical data , Papillomavirus Vaccines/administration & dosage , Vaccination Coverage/statistics & numerical data , Adolescent , Australian Capital Territory/epidemiology , Child , Female , Humans , Immunization Programs/statistics & numerical data , Indigenous Peoples , Male , New South Wales/epidemiology , Northern Territory/epidemiology , Queensland/epidemiology , Uterine Cervical Neoplasms/prevention & controlABSTRACT
BACKGROUND: In 2007, Australia was one of the first countries to introduce a national human papillomavirus (HPV) vaccination programme, and it has since achieved high vaccination coverage across both sexes. In December, 2017, organised cervical screening in Australia transitioned from cytology-based screening every 2 years for women aged from 18-20 years to 69 years, to primary HPV testing every 5 years for women aged 25-69 years and exit testing for women aged 70-74 years. We aimed to identify the earliest years in which the annual age-standardised incidence of cervical cancer in Australia (which is currently seven cases per 100â000 women) could decrease below two annual thresholds that could be considered to be potential elimination thresholds: a rare cancer threshold (six new cases per 100â000 women) or a lower threshold (four new cases per 100â000 women), since Australia is likely to be one of the first countries to reach these benchmarks. METHODS: In this modelling study, we used Policy1-Cervix-an extensively validated dynamic model of HPV vaccination, natural history, and cervical screening-to estimate the age-standardised incidence of cervical cancer in Australia from 2015 to 2100. We incorporated age-specific coverage of the Australian National HPV Vaccination Program in girls, including the catch-up programme, and the inclusion of boys into the vaccine programme from 2013, and a change from the quadrivalent to the nonavalent vaccine from 2018. We also modelled the effects of the transition to primary HPV screening. We considered two scenarios for future screening recommendations regarding the cohorts who will be and who have been offered the nonavalent vaccine: either that HPV screening every 5 years continues, or that no screening would be offered to these women. FINDINGS: We estimate that, in Australia, the age-standardised annual incidence of cervical cancer will decrease to fewer than six new cases per 100â000 women by 2020 (range 2018-22), and to fewer than four new cases per 100â000 women by 2028 (2021-35). The precise year of attaining these rates is dependent on the population used for age-standardisation, HPV screening behaviour and test characteristics, the incremental effects of vaccination of men on herd immunity in women, and assumptions about the future frequency of benign hysterectomies. By 2066 (2054-77), the annual incidence of cervical cancer will decrease and remain at fewer than one case per 100â000 women if screening for HPV every 5 years continues for cohorts who have been offered the nonavalent vaccine, or fewer than three cases per 100â000 women if these cohorts are not screened. Cervical cancer mortality is estimated to decrease to less than an age-standardised annual rate of one death per 100â000 women by 2034 (2025-47), even if future screening is only offered to older cohorts that were not offered the nonavalent vaccine. INTERPRETATION: If high-coverage vaccination and screening is maintained, at an elimination threshold of four new cases per 100â000 women annually, cervical cancer could be considered to be eliminated as a public health problem in Australia within the next 20 years. However, screening and vaccination initiatives would need to be maintained thereafter to maintain very low cervical cancer incidence and mortality rates. FUNDING: National Health and Medical Research Council (Australia).
Subject(s)
Models, Statistical , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/therapeutic use , Uterine Cervical Neoplasms/epidemiology , Adolescent , Adult , Age Distribution , Aged , Australia/epidemiology , Female , Humans , Incidence , Middle Aged , Young AdultABSTRACT
Australia's transition to primary human papillomavirus (HPV) based cervical screening, has for the first time, provided a passive mechanism for monitoring the impact of vaccination on infection prevalence among women attending screening. We assessed oncogenic HPV prevalence by single year of age in the first 7⯠months of the program, using data collected from a large screening laboratory in Victoria, Australia, which is routinely screening using cobas 4800, cobas 6800 and Seegene assays. Among 116,052 primary screening samples from women aged 25-74, 9.25% (95%CI: 9.09-9.42%) had oncogenic HPV detected: 2.14% (95%CI: 2.05-2.22%) were 16/18 positive and 7.12% (95%CI: 6.97-7.27%) were positive for only non-16/18 HPV. Prevalence peaked at age 25-29 then decreased with age, but this was driven by non-16/18 types. HPV16/18 prevalence remained low and flat across ages, contrasting with pre-vaccination epidemiology when HPV16/18 peaked in young women. HPV-based screening can precisely monitor HPV prevalence.
Subject(s)
Age Factors , Cervix Uteri/virology , Mass Screening/statistics & numerical data , Papillomavirus Infections/epidemiology , Papillomavirus Vaccines/therapeutic use , Vaccination/statistics & numerical data , Adult , Aged , Australia/epidemiology , Early Detection of Cancer , Female , Genotype , Human papillomavirus 16 , Human papillomavirus 18 , Humans , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/prevention & control , Prevalence , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Dysplasia/prevention & control , Uterine Cervical Dysplasia/virologyABSTRACT
OBJECTIVE: Cervical cancer mortality has halved in Australia since the national cervical screening program began in 1991, but elevated mortality rates persist for Aboriginal and Torres Strait Islander women (referred to as Aboriginal women in this report). We investigated differences by Aboriginal status in abnormality rates predicted by cervical cytology and confirmed by histological diagnoses among screened women. METHODS: Using record linkage between cervical screening registry and public hospital records in South Australia, we obtained Aboriginal status of women aged 20-69 for 1993-2016 (this was not recorded by the registry). Differences in cytological abnormalities were investigated by Aboriginal status, using relative risk ratios from mixed effect multinomial logistic regression modelling. Odds ratios were calculated for histological high grade results for Aboriginal compared with non-Aboriginal women. RESULTS: Of 1,676,141 linkable cytology tests, 5.8% were abnormal. Abnormal results were more common for women who were younger, never married, and living in a major city or socioeconomically disadvantaged area. After adjusting for these factors and numbers of screening episodes, the relative risk of a low grade cytological abnormality compared with a normal test was 14% (95% confidence interval 5-24%) higher, and the relative risk of a high grade cytological abnormality was 61% (95% confidence interval 44-79%) higher, for Aboriginal women. The adjusted odds ratio of a histological high grade was 76% (95% confidence interval 46-113%) higher. CONCLUSIONS: Ensuring that screen-detected abnormalities are followed up in a timely way by culturally acceptable services is important for reducing differences in cervical cancer rates between Aboriginal and non-Aboriginal women.