The combined impact of implementing HPV immunisation and primary HPV screening in New Zealand: Transitional and long-term benefits, costs and resource utilisation implications.

BACKGROUND: In response to emergent evidence, many countries are transitioning from cytology-based to HPV screening. We evaluated the impact of an upcoming transition on health outcomes and resource utilisation in New Zealand. METHODS: An extensively validated model of HPV transmission, vaccination, natural history and cervical screening ('Policy1-Cervix') was utilised to simulate a transition from three-yearly cytology for women 20-69 years to five-yearly HPV screening with 16/18 genotyping for women 25-69 years, accounting for population growth and the impact of HPV immunisation. Cervical cancer rates, resources use (test volumes), costs, and test positivity rates from 2015 to 2035 were estimated. FINDINGS: By 2035, the transition to HPV screening will result in declines in cervical cancer incidence and mortality rates by 32% and 25%, respectively, compared to 2018. A potentially detectable 5% increase in cervical cancer incidence due to earlier detection is predicted for the year of transition. Annual numbers of women screened will fluctuate with the five-year screening interval. Cytology volumes will reduce by over 80% but colposcopy volumes will be similar to pre-transition rates, and program costs will be reduced by 16%. A 9% HPV test positivity rate is expected in the first round of HPV screening (2019-2023), with 2.7% of women referred for colposcopy. Transitioning from cytology to primary HPV cervical screening could avert 149 cancer cases and 45 deaths by 2035. CONCLUSION: Primary HPV screening and vaccination will reduce cervical cancer and resources use. A small transient apparent increase of invasive cancer rates due to earlier detection may be detectable at the population level, reflecting the introduction of a more sensitive screening test. These findings can be used to inform health services planning and public communications surrounding program implementation.

Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand.

BACKGROUND: New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20-69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). METHODS: A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. RESULTS: Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25-69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12-16% and to save 4-13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. CONCLUSION: Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ.

Pre-vaccination type-specific HPV prevalence in confirmed cervical high grade lesions in the Maori and non-Maori populations in New Zealand.

BACKGROUND: New Zealand initiated HPV vaccination in 2008, and has attained 3-dose coverage of ~50 % in 12-13 year old girls. Due to the success of program initiatives in Maori girls, higher coverage rates of ~60 % have been achieved in this group. We have previously reported a benchmark overall pre-vaccination prevalence of oncogenic HPV infection in high grade cervical lesions in New Zealand. The current extended analysis provides separate pre-vaccination benchmark prevalence for Maori and non-Maori women. METHODS: The National Cervical Screening Programme Register (NCSP-R) was used to identify any woman aged 20-69 years of age with an index high grade cytology report from 2009-2011. Extended recruitment was performed until 2012 in clinics with a high proportion of Maori women. Ethnicity status was based on self-reported information by participating women through phone contact supplemented by recordings on the study questionnaire (the NCSP-R was not used to extract ethnicity status). A total of 730 women consented to participate and had a valid HPV test result; 418 of these had histologically-confirmed cervical intraepithelial neoplasia (CIN) 2/3 lesions (149 Maori, 269 non-Maori). The prevalence of any cervical oncogenic HPV infection, HPV16, and HPV18 was calculated in women with CIN2/3. RESULTS: In confirmed CIN2/3, the prevalence of any oncogenic HPV, HPV16 and HPV18 was 96 % (95 % CI:91-99 %), 54 % (95 % CI:46-63 %), 11 % (95 % CI:7-18 %) in Maori and 96 % (95 % CI:93-98 %), 54 % (95 % CI:48-60 %), 11 % (95 % CI:7-15 %) in non-Maori women, respectively. Age-specific patterns of infection for HPV16/18 in confirmed CIN2/3 differed between the two groups (Pinteraction = 0.02), with a lower prevalence in younger vs. older Maori women (57 % in 20-29 years vs 75 % in 40-69 years) but a higher prevalence in younger vs. older non-Maori women (70 % in 20-29 years vs 49 % in 40-69 years); the difference in the age-specific patterns of infection for HPV16/18 was not significant either when considering confirmed CIN2 alone (p = 0.09) or CIN3 alone (p = 0.22). CONCLUSIONS: The overall prevalence of vaccine-included types in CIN2/3 was similar in Maori and non-Maori women, implying that the long-term effects of vaccination will be similar in the two groups.

Type-specific oncogenic human papillomavirus infection in high grade cervical disease in New Zealand.

BACKGROUND: The national Human Papillomavirus (HPV) Immunisation Programme in New Zealand was introduced in 2008, and involves routine vaccination of girls 12-13 years with a catch-up for females aged up to 19 years. The aims of this study were to measure the pre-vaccination prevalence of oncogenic HPV infection in women aged 20-69 years who were participating in the New Zealand National Cervical Screening Programme (NZ-NCSP) and who were: (1) referred with high grade cytology with a subsequent histologically-confirmed high grade cervical intraepithelial neoplasia (CIN2/3) or adenocarcinoma in situ (AIS); or (2) were in the wider group of women who had a cytological prediction of high grade squamous disease or glandular abnormality (ASC-H/ HSIL+/AGC/AIS). METHODS: Women aged 20-69 years appearing on the NZ-NCSP register between August 2009-February 2011 with a cytology record of ASC-H/HSIL+/AGC/AIS were invited to participate in the study. Liquid-based cytology specimens were tested for 37 HPV types using Linear Array genotyping. The prevalence of type-specific HPV infection was reported within women with histologically-confirmed CIN 2/3 and within the wider group with ASC-H/HSIL+/AGC/AIS cytology. Age-specific trends for the relative proportion of HPV 16/18 vs. other oncogenic types in CIN2/3 were assessed. RESULTS: A total of 594 women with ASC-H/HSIL+/AGC/AIS cytology and a valid HPV test were recruited; of these 356 (60%) had confirmed CIN2/3 and 6 (1%) had confirmed AIS or glandular dysplasia. Positivity rates for any oncogenic HPV infection and for HPV16 and/or 18 within confirmed CIN2/3-AIS were 95% (95%CI: 92-97%) and 60% (54-65%) respectively; in all women with ASC-H/HSIL+/AGC/AIS cytology it was 87% (84-89%) and 53% (49-57%), respectively. The most common reported HPV types in women with CIN 2/3 were 16 (51%), 52 (19%), 31 (17%), 33 (13%) and 18 (12%). A trend for higher rates of HPV 16/18 infection compared to other oncogenic types was observed in younger women (p=0.0006). CONCLUSIONS: The prevalence of HPV 16/18 in confirmed high grade disease in New Zealand is comparable to that observed in Australia and European countries. Test positivity rates for type 52 appear higher than in comparable studies in other developed countries. A greater proportion of high grade lesions in younger women appear to be associated with HPV 16/18 infection.

Monitoring the performance of New Zealand's National Cervical Screening Programme through data linkage.

AIM: To describe the method developed by the National Cervical Screening Programme (NCSP) for review of cases of cervical cancer; present results from the first 4 years of the review and compare these results with those of the earlier New Zealand Cervical Cancer Audit. METHODS: Linkage of cervical cancer registrations from the New Zealand Cancer Registry to smear histories from the NCSP Register via the National Health Index, for the 4-year period 2003-06. RESULTS: A total of 625 women were registered with cervical cancer from 2003-06, of whom 438 were eligible for linkage (women diagnosed with squamous or adenosquamous cervical cancer at <80 years of age). Of these 438 eligible cases, 348 were histologically invasive and 90 were microinvasive. Unlike histological stage, clinical FIGO stage was missing in approximately 50%. Linkage to screening history revealed that 202 of the 438 eligible women (46%) had never been enrolled in the NCSP; 137 (31%) were enrolled but had only been infrequently or irregularly screened; and 85 (20%) developed cancer despite regular screening (data were missing for 3 women). These results were similar to those found in the New Zealand Cervical Cancer Audit, covering the period 2000-2002. CONCLUSIONS: Ongoing linkage of cancer data to screening data can be used to monitor the performance of the NCSP. Our finding that 80% of potentially preventable cervical cancers involve women who are not enrolled in the Programme or who have been only infrequently and irregularly screened, confirms that improving Programme coverage (currently around 72%) remains a priority. Further investigation (phase 2) is required for the small number of women who develop cervical cancer despite regular screening (average of 21 per year, or approximately 20% of eligible cases), to distinguish interval cancers from possible Programme quality issues.