Human papillomavirus load and genotype analysis improves the prediction of invasive cervical cancer

Abstract

Human papillomavirus (HPV)-based cervical screening is a globally recommended health policy. Different HPV types have different risk for cervical cancer. For optimal HPV screening, the sensitivity and specificity for each HPV type at different viral loads should be known in a screening setting. HPV test results in about 1 million cervical samples analyzed during 2006 to 2014 were compared for 319 women who had developed invasive cervical cancer up to 8.5 years later and for 1911 matched control women. Detection including low viral loads resulted in markedly increased sensitivity for cervical cancer only for HPV types 16 and 18. Testing for HPV types 31, 33, 45 and 52 also increased the sensitivity for prediction of cervical cancer, but for these viruses, detection of low viral load did not further increase sensitivity. HPV types 35, 39, 51, 56, 58, 59, 66 and 68 only predicted occasional additional cervical cancer cases.Testing for HPV16/18 at low viral load plus testing for HPV31, 33, 45 and 52 at >3000 copies/μL predicted 86.5% of cancers occurring within a year after testing, similar to the 89.4% that were predicted by testing for 14 HPV types. By contrast, the type and viral load-restricted testing greatly increased specificity: 6.3% of healthy women tested positive as compared to 11.7% of healthy women testing positive for the 14 HPV types commonly screened for today. Adequate HPV screening sensitivity, with considerable increase in specificity, can be obtained by testing only for HPV16/18/31/33/45/52, with detection of low viral load required only for HPV16/18.

Divergent effects of switching from cytology to HPV-based screening in the Nordic countries

“… 32 Triage algorithms utilizing genotyping and viral load could also reduce overdiagnosis as genotypes differ in their likelihood to progress to invasive cancer. 33 Partial genotyping was implemented in Norway from 1 July 2018 onwards, where only women tested positive for genotypes 16 or 18 with low-grade abnormal cytology were referred to diagnostic confirmation. The Swedish screening programme has taken a step further and will implement extended genotyping in the routine programme by classifying HPV genotypes to high risk (HPV types 16, 18 and 45), medium risk (HPV types 31, 33, 52 and 58) and low risk (other hrHPV types) and apply different management pathways based on this grouping.…”

Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells

“…We ranked cervical cancer risk according to the following hierarchy: HPV16, 18, 45, 31, 33, 52, 35, 39, 51, 56, 58, 59, 68. 18,19 Oncogenic HPV types that rarely cause cervical cancer in Europe 20,21 (35/39/51/56/58/59/68) were grouped as low-risk oncogenic HPV types. The presence of nononcogenic HPV types (11/30/42/66/ 67/70/74/81/82/83/90) was observed in a number of cases.…”

Alternative cytology triage strategies for primary HPV screening

“…HPV screening also enables self-sampling, which may increase screening coverage [13]. The downside of primary HPV screening is its lower specificity compared to primary cytology screening [2] which causes higher colposcopy referral rates and detection of non-progressive CIN lesions [14,15]. Pre-cancer treatments can cause adverse effects for the examined individuals, including pain, bleeding, discharge and psychological distress, and an increased risk of adverse obstetric outcomes [16].…”