Clinical relevance of partial HPV16/18 genotyping in stratifying HPV-positive women attending routine cervical cancer screening: a population-based cohort study.

OBJECTIVE: To evaluate partial HPV16/18 genotyping as a possible biomarker to select women attending HPV-based cervical cancer screening at higher risk to be referred to colposcopy. DESIGN: Population-based cohort study. SETTING: Organised cervical cancer screening programmes (Italy). POPULATION: Women with high-risk HPV infection (period: 2015-2019). METHODS: We analysed the association between partial HPV16/18 genotyping, cytology triage and histologically confirmed diagnosis of high-grade cervical intraepithelial neoplasia (CIN3+ ) lesions. MAIN OUTCOME MEASURES: Detection rate (DR) and positive predictive value (PPV) for histologically confirmed CIN3+ (any episode in the 2 years after baseline); sensitivity for CIN3+ and number of colposcopies needed for lesion detection. RESULTS: The study included 145 437 women screened with HPV testing by the clinically validated COBAS 4800 HPV assay (Roche). Overall, 9601 (6.6%) women were HPV+ at baseline; HPV16 and HPV18 were present in 1865 and 594 samples, respectively. The cumulative (baseline plus 1-year repeat) cytology positivity was 42.8% and high-grade cytology was significantly higher (P < 0.0001) among women with HPV16 infection at baseline (15.2%). The cumulative CIN3+ DR for women with HPV16, HPV18 and other HPV-type infections was 9.8%, 3.4% and 1.8%, respectively. CONCLUSIONS: Partial HPV16 genotyping may play a role in triage, whereas HPV18 seems to behave much more similarly to the other HPV types and does not provide additional stratification. HPV16 genotyping combined with high-grade cytology can be envisaged as a triage biomarker in cervical screening to maximise CIN3+ detection while minimising colposcopy at baseline or 1-year repeat. TWEETABLE ABSTRACT: HPV16 genotyping combined with high-grade cytology can be used as triage biomarker for CIN3+ in HPV-positive women.

Age-related changes in the diagnostic assessment of women with severe cervical lesions.

OBJECTIVES: To evaluate the effect of age on the diagnostic assessment of women with severe cervical intraepithelial neoplasia (CIN). METHODS: This retrospective observational study included 338 consecutive women with a diagnosis of CIN3 on cone specimen. Patients were divided into three groups according to age: < 35 years (Group A), 35-49 years (Group B), and ≥ 50 years (Group C). Clinical and colposcopic variables were compared, and human papillomavirus (HPV) genotype distribution was measured. RESULTS: The most common HPV genotype was HPV-16 (63.65%), followed by HPV-33 (7%), HPV-18 (6.2%), and HPV-31 (5.4%). The rate of the following high-grade lesion predictors was lower in Group C than in Groups A and B: HPV-16 infections (55.9% vs. 75% vs. 70.9%, respectively, p = 0.022); high-grade colposcopic impression (29.4% vs. 51.8% vs. 51.7%, respectively, p < 0.0001); and high-grade cytological changes (30.9% vs. 56.2% vs. 45.4%, respectively, p = 0.025). An endocervical lesion location was more frequent in Group C than in Groups A and B (55.6% vs. 6.8% vs. 11.8%, respectively, p < 0.0001). CONCLUSION: Women aged 50 years and older with CIN3 showed a significant reduction of high-grade lesion predictors along with physiological confounding cervical changes (transformation zone type 3 and endocervical lesion location). The diagnostic work-up of cervical lesions in older women should provide their potential consideration as a special population.

Molecular diagnostics of pulmonary metastasis from cervical cancer.

High-risk human papillomaviruses (HPV) are largely implicated in the carcinogenesis of cervical carcinomas. Their role in lung carcinomas, however, is still unclear. We describe the case of 44-year-old female chain-smoker with previous HPV-related cervical cancer and a new distant tumour in the lung after many years. The histologic distinction between metastatic squamous cell carcinoma of the cervix and another primary squamous cell tumour of the lung can be difficult and has important clinical implications. The aim of our study was to investigate whether HPV was present in both the patient's cervical cancer and her subsequent primary lung cancer in order to appropriately plan therapy. We tested both the paraffin-embedded tissue of the cervical cancer and the lung cancer for HPV DNA using the Qiagen HPV Sign Genotyping Test, which detected HPV16-DNA in both tumours. The Qiagen HPV Sign Genotyping Test is a reliable method to detect HPV-DNA in tissue and cytological materials, thus making it possible to distinguish metastatic cervical carcinoma from a new primary tumour in different sites.