Clustering patterns of type‐type combination in multiple genotypes infections of human papillomavirus in cervical adenocarcinoma

Abstract

Coinfections with multiple types of human papillomavirus (HPV) occur in cervical adenocarcinoma (ADC). However, it remains unclear the clustering patterns of multiple types in HPV coinfections and relevant factors in ADC. A total of 718 paraffin-embedded ADC specimens were collected in China and tested for HPV genotypes using SPF10-INNO-LIPA. The prevalence of HPV coinfections and clustering patterns by geographical regions, histological subtypes and ages were assessed. Type-specific attribution of HPV to ADC adjusted by HPV coinfections were calculated. The prevalence of HPV coinfections was found to be 8.4% in ADC cases with slight variation by geographic regions between 2.2% and 12.5%. The 88.3% of all HPV multiple infections in ADC were two types of HPV coinfections with predominant combination of HPV 16 and HPV 18. The attribution to ADC was 88.0% for HPV 16/18 targeted by bivalent and quadrivalent vaccine and 96.8% for HPV 16/ 18/31/33/45/52/58 targeted by nonavalent vaccine. Clustering patterns of multiple types were related with histological categories and age at diagnosis. In conclusion, HPV coinfections are uncommonly prevalent in ADC cases with slight variation by geographic regions and distinct clustering patterns of multiple types by histological subtypes and ages at diagnosis. The high attribution of carcinogenic HPV types to ADC predicts potential protection of HPV vaccine against ADC. K E Y W O R D S cervical adenocarcinoma, clustering patterns, human papillomavirus, multiple genotypes 1 | INTRODUCTION Cervical adenocarcinoma (ADC), a histological subtype of cervical cancer, composes approximately 10% to 20% of all cervical cancer cases. 1,2 In contrast with the declined incidence of squamous cell cancer in an era of ever-increasing coverage of cervical cancer screening and human papillomavirus (HPV) vaccine, ADC has become more common in the past decades, even in countries with organized screening. 3-6 The estimated global incidence of ADC was 1.6 cases per 100 000 women, and approximately 56 805 new cases developed worldwide in 2015. 2 Persistent infection with high-risk types of HPV has been established as an essential cause of cervical cancer. 7,8 Over 200 types of HPV out of more than 350 different papillomaviruses Li Dong and Tingyuan Li contributed equally to this work.

Current Updates on Cancer-Causing Types of Human Papillomaviruses (HPVs) in East, Southeast, and South Asia

“…The other most prevalent hrHPV genotypes include HPV31 (1.37–8.89%), HPV33 (0.74–9.1%), HPV35 (0.5–3.2%), HPV39 (0.7–13.33%), HPV45 (0.8–9.1%), HPV51 (0.3–18.8%), HPV52 (1.08–40.74%), HPV56 (0.2–9%), HPV58 (1.9–15.6%), HPV59 (0.6–4.4%), and HPV68 (0.4–11.11%) [ 56 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. The HPV detection rate was also found to increase as lesions progress from precancerous (low-grade squamous intraepithelial (LSIL) at 48.12–91.5% and high-grade squamous intraepithelial lesion (HSIL) at 75.6–99.5%) to cancerous (invasive cervical cancer (ICC) at 64.3–100%) [ 56 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. The detailed prevalence of hrHPV genotypes detected in different stages of cervical lesions by regions and countries is summarized in Table 1 .…”

“…The overall HPV-positive detection rate in normal women ranges from 7.2% (Malaysia) to 41.7% (Hong Kong). The HPV genotypes commonly detected in these regions are HPV16, 18,52,58,31,33,35,39,45,51,56,59,68,6,11,42,43, and 81 .…”

“…The hrHPV genotypes that are most frequently detected in cervical lesions are HPV16, 18,31,33,35,39,45,51,52,56,58,59, and 68 [61][62][63][64][65][66][67][68][69][70][71]. As previously mentioned, the HPVpositive rate has been found to increase as lesions progress from low grade (LSIL) (78.2-85.8%) and HSIL (75.6-100%)) to high grade (ICC (64.3-100%)) lesions.…”

LINC00963 May Be Associated with a Poor Prognosis in Patients with Cervical Cancer

“…Cervical cancer comprises 4 main types: cervical squamous cell carcinoma and adenocarcinoma, which account for approximately 95% of all cases, followed by adenosquamous carcinoma and adenoid basal cell carcinoma, which account for approximately 5% of all cases. The incidence of cervical and endocervical cancer (CESC) has increased markedly, becoming the most predominant subtype of cervical cancer detected among Chinese patients [ 2 ].…”

Genetic and Epigenetic Variations of HPV52 in Cervical Precancer

“…The distribution of these HR-HPVs varies geographically across continents, particularly HPV52 and HPV58, whose prevalence is notably higher in cases of invasive cervical cancer in Asia [ 5 , 6 ], though also frequently detected in Brazil, according to a recent report [ 7 ]. For example, HPV52 is the fourth most frequent HPV type detected in cervical cancer cases in China [ 8 ]. Many countries in Africa and Asia have yet to introduce the recently FDA-approved nonavalent HPV vaccine that includes HPV52 [ 9 ], and until the vaccine is implemented, these regions will continue to encounter a high burden of HPV52-related cervix cancer deaths [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”