ABSTRACT
Objective:To evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with vaginal self-sampling in primary screening and combining cytology or viral load for HR-HPV positive as secondary screening strategies.Methods:The data referring to HR-HPV genotyping of self-collected sample with mass array matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April 2009 and April 2010. The data were reanalyzed to determine the sensitivity and specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN Ⅱ +), CIN of grade 3 or worse (CIN Ⅲ +) when HR-HPV genotyping combining with colposcopy as primary screening strategy based on varied HR-HPV subtype (strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV 16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52 positive; 1e: any HR-HPV positive). The data were also compared to determine the efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d, 2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c, 3d) of physician-collected sample as a triage with HR-HPV genotyping for self-sampling HR-HPV positives. Results:(1) The HR-HPV positive rate was 13.77% (1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV 16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556) and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results ≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1 031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱ +, CIN Ⅲ + which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the lowest specificity and positive predictive value (PPV). Meanwhile,the required colposcopy referral rates were much higher than other 13 sub-strategies (13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a had the highest specificities for CIN Ⅱ + and CIN Ⅲ + (97.92%, 97.69%, respectively), while 1d had the highest sensitivities for CIN Ⅱ + and CIN Ⅲ + (88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling HPV 16/18 positives for immediate colposcopy followed by triage physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for non-HPV 16/18 positives had significantly higher sensitivity and specificity for CIN Ⅱ, CIN Ⅲ +, as well as lower referral rates (strategy 2a and 3a). Additionally, based on these two secondary screening strategies, cumulatively using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for immediate colposcopy showed an enhanced sensitivity. Conclusions:Primary HR-HPV cervical cancer screening strategy based on self-sampling with triage of cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among sensitivity, specificity for CIN Ⅱ + and CIN Ⅲ + and the number of tests required, referral rates. The efficacy of HR-HPV genotyping combining cytology or viral load secondary screening strategies will have a spiral escalation when HPV 58, 31, 33, 52 are included.
ABSTRACT
Objective@#To determine the morbidity of cervical intraepithelial neoplasia 2+ (CIN2+ ) and CIN3+ of different human papillomavirus(HPV) subtype infection combined with different cytology status.@*Methods@#The Shenzhen Cervical Cancer Screening Trial Ⅰ & Ⅱ (SHENCCASTⅠ&Ⅱ) are population-based cross-sectional cervical cancer screening studis conducted in Shenzhen and surrounding area from 2008 to 2010. A total of 12 097 women who aged 25-59 years were included in the analysis. All of these women were detected by liquid-based cytology test and several high-risk HPV-DNA tests. The ones with HPV positive or atypical squamous cells of undetermined sign (ASC-US) were sequentially conducted by cervical biopsy vaginoscopy. Finally, 10 805 samples with complete data of hybrid capture 2(HC2), the polymerase chain reaction-based matrix-assisted laser desorption/ionization time-of-flight assay (MALDI-TOF), HPV genotyping detection, cytology and pathology results were analyzed.@*Results@#The top 6 infection rates of HR-HPV in CIN2+ and CIN3+ were HPV16, HPV52, HPV58, HPV33, HPV31, HPV18. The highest constituent ratio of cytology in CIN2+ and CIN3+ was high grade squamous intraepithelial lesion(HSIL). The morbidities of CIN2+ of patients infected with HPV16, HPV31, HPV58, HPV33, HPV18, HPV52 were 41.3%, 31.5%, 30.6%, 28.7%, 28.2%, 17.7%, respectively, while the morbidities of CIN3+ of those were 33.5%, 20.5%, 19.4%, 15.7%, 19.2%, 8.3%, respectively.The morbidities of CIN2+ in negative intraepithelial lesion or malignancy (NILM), ASC-US, low grade squamous intraepithelial lesion (LSIL), atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial lesion (HSIL), atypical glandular cell (AGC) samples were 0.4%, 6.9%, 11.1%, 36.4%, 82.0%, 16.7%, respectively, while the morbidities of CIN3+ of those were 0.2%, 3.1%, 4.2%, 22.7%, 64.8%, 0.0%, respectively. The morbidities of CIN2+ in NILM combined with HPV16, HPV18, HPV31, HPV33 infection were 12.6%, 13.3%, 15.8% and 11.5%, respectively, while the morbidities of CIN3+ of those were 10.3%, 11.1%, 7.9% and 7.7%, respectively.The morbidities of CIN2+ and CIN3+ in ASC-US combining with hrHPV infection were high, and the top 6 subtypes associated with high risk of CIN2+ were HPV31 (35.7%), HPV33 (26.9%), HPV16 (26.5%), HPV58 (22.4%), HPV52 (18.6%), HPV68 (15.4%), while those associated with high risk of CIN3+ were HPV16 (20.4%), HPV31 (14.3%), HPV33 (11.5%), HPV58 (8.6%), HPV68 (7.7%), HPV52 (5.8%).@*Conclusions@#Cytology combined with HPV genotyping detection can more effectively estimate the morbidity risks of CIN2+ and CIN3+ . Both high prevalence rates and high risks associated with CIN2+ and CIN3+ of HPV31, HPV33, HPV52 and HPV58 are observed. NILM and ASC-US status combined with these subtypes mentioned above are advised to be conducted by colposcopy.