Andrzej Nowakowski

HPV testing in Polish population-based cervical cancer screening programme (HIPPO project)—study protocol of a randomised healthcare policy trial

Abstract Background An Organised Cervical Cancer Screening Programme (OCCSP) was started in Poland in 2006/2007. Each woman aged 25 to 59 is eligible for a free Pap test every 3 years in OCCSP. Despite implementation of the OCCSP, the age-standardised cervical cancer (CC) incidence and mortality rates in 2019 were 7.3/100 000 and 3.9/100 000 respectively and were still higher than those in Western European countries with well-organised screening programmes. Apart from low coverage of the OCCSP, suboptimal performance of the screening test (conventional cytology) may be partially responsible for this situation. Several countries have already incorporated high risk Human Papillomavirus (hrHPV) testing in CC screening as a more sensitive tool reducing the risk of missing precancerous lesions and allowing for extension of screening intervals. The European Guidelines for Quality Assurance in Cervical Cancer Screening recommend pilot evaluation of a new screening test in country-specific conditions before its implementation. Methods The HIPPO project (HPV testing In Polish POpulation-based cervical cancer screening program) is a randomised health services study nested in the OCCSP in Poland. The project will randomise 33 000 women aged 30–59 years to cytology or hrHPV testing (ratio: 1:1) with age stratification. In the cytology arm women with repeated Atypical Squamous Cells of Undetermined Significance (ASC-US) or ≥ Low–Grade Squamous Intraepithelial Lesions (LSIL) are referred for colposcopy. In the other arm, hrHPV ( +) women with ≥ ASC-US reflex Liquid-Based Cytology (LBC) are referred for colposcopy. Primary endpoints include detection rates of histologically confirmed high grade intraepithelial lesions or worse (CIN2 +) in each arm. Discussion This pilot randomised healthcare study nested in the OCCSP in Poland will assess and compare the performance of hrHPV testing to current standard—cytology in order to make decisions on implementation of HPV-based screening in the country. Trial registration This randomised healthcare service study was prospectively registered at https://clinicaltrials.gov/ (identifier: NCT04111835, protocol ID 28/2019) on 19th of September 2019.

Lack of consensus in calculation of interval cancer rates for cervical cancer screening

AbstractIntroductionIn 2018, nondisclosure of results of retrospective audits of cytology in interval cancers precipitated a crisis in the Irish national cervical screening programme. In response, an Expert Reference Group was convened which recommended a collaborative approach to the development of a new key performance indicator, the interval cancer rate. The Expert Reference Group also recommended that the Irish programme should collaborate with international colleagues to reach consensus on (i) the definition of an interval cervical cancer, (ii) the methodology to calculate the interval cancer rate, and (iii) benchmarking with other international programs. This study was undertaken to determine if a consensus regarding the definition of an interval cervical cancer and the calculation of an interval cancer rate exists.Material and MethodsA web‐based questionnaire was sent to 18 population‐based cervical screening programs. Inclusion criteria involved (1) a national or regional population‐based cervical screening prograe; (2) a country or region with a population ≥population of Ireland; (3) programs located in Europe, Australia, or Canada; (4) programs that had responded to a previously published international survey on the disclosure of retrospective cytology reviews in cervical cancer cases.ResultsThe response rate was nine out of 18. Of nine respondents, six had an agreed definition of interval cervical cancer, and four of these calculated an interval cancer rate. Three programs neither calculated interval cancer rates nor had any guidelines related to this. Of the six with an agreed definition, all respondents defined the numerator as invasive cancers in the screening age group, with four including microinvasive disease. Respondents included cancers diagnosed 3–5 years after the last screening test had been taken. Three respondents also included cancers diagnosed in women up to 3.5 years after they exited the screening program. Countries use different denominators, including (i) per women years, (ii) per number of screens, and (iii) per total cancers in screened population.ConclusionsThere is variation in the parameters used in interval cancer rate calculation. To allow benchmarking of cervical screening program performance, there is a need for consensus on a standardized method of interval cancer definition and interval cancer rate calculation.

Cervical microbiota dysbiosis associated with high-risk Human Papillomavirus infection

High-risk Human Papillomavirus (HR-HPV) genotypes, specifically HPV16 and HPV18, pose a significant risk for the development of cervical intraepithelial neoplasia and cervical cancer. In the multifaceted cervical microenvironment, consisting of immune cells and diverse microbiota, Lactobacillus emerges as a pivotal factor, wielding significant influence in both stabilizing and disrupting the microbiome of the reproductive tract. To analyze the distinction between the cervical microbiota and Lactobacillus-dominant/non-dominant status of HR-HPV and non-infected healthy women, sixty-nine cervical swab samples were analyzed, included 44 with HR-HPV infection and healthy controls. All samples were recruited from Human Papillomavirus-based cervical cancer screening program and subjected to 16s rRNA sequencing analysis. Alpha and beta diversity analyses reveal no significant differences in the cervical microbiota of HR-HPV-infected women, including 16 and 18 HPV genotypes, and those with squamous intraepithelial lesion (SIL), compared to a control group. In this study we identified significantly lower abundance of Lactobacillus mucosae in women with HR-HPV infection compared to the control group. Furthermore, changes in bacterial diversity were noted in Lactobacillus non-dominant (LND) samples compared to Lactobacillus-dominant (LD) in both HR-HPV-infected and control groups. LND samples in HR-HPV-infected women exhibited a cervical dysbiotic state, characterized by Lactobacillus deficiency. In turn, the LD HR-HPV group showed an overrepresentation of Lactobacillus helveticus. In summary, our study highlighted the distinctive roles of L. mucosae and L. helveticus in HR-HPV infections, signaling a need for further research to demonstrate potential clinical implications of cervical microbiota dysbiosis.

HPV Testing In Polish POpulation-based Cervical Cancer Screening Program.

The HIPPO PROJECT is a randomized healthcare study nested in the OCCSP in Poland. This project will assess the performance of the new screening test (HR HPV test) before its implementation in Poland.