Multiple Human Papillomavirus Infections with High Viral Loads Are Associated with Cervical Lesions but Do Not Differentiate Grades of Cervical Abnormalities

Abstract

Multiple human papillomavirus (HPV) genotypes often coexist within cervical epithelia and are frequently detected together in smears of different grades of cervical neoplasia. Describing the association between multiple infections and cervical disease is important in generating hypotheses regarding its pathogenesis. We analyzed the prevalence of multiple HPV infections and their attribution to cervical disease in a screening population of 999 consecutive BD SurePath liquid-based cervical cytology samples enriched with atypical squamous cells of undetermined significance (ASCUS) (n ‫؍‬ 100), low-grade squamous intraepithelial lesions (LSIL) (n ‫؍‬ 100), and high-grade squamous intraepithelial lesions (HSIL) (n ‫؍‬ 97). HPV genotyping was performed only on cytology specimens using a broad-spectrum GP5 ؉ /6 ؉ -PCR/multiplex HPV genotyping (BSGP5 ؉ /6 ؉ -PCR/MPG) assay that detects and quantifies 51 HPV genotypes and 3 subtypes. Using a recently defined high viral load cutoff, the quantitative data were scored as high or low viral load. In the 36-month follow-up, 79 histologically confirmed cervical intraepithelial neoplasia grade 2 or greater (CIN2؉) cases were identified. In the screening population, there was a trend of having more multiple infections at a younger age. Multiple HPV infections were common. Multiple HPV types were most prevalent in LSIL (75.9% of HPV positives), followed by HSIL (65.5%), ASCUS (64.6%), and negative for intraepithelial lesion or malignancy (NILM) (36.8%). On average, 3.2 and 2.5 HPV types were detected per LSIL and HSIL sample, respectively. Multiple HPV types with high viral loads were most prevalent in LSIL (62.6% of high viral load positives), followed by HSIL (51.9%), ASCUS (40.7%), and NILM (19.3%). Patients with multiple high viral loads showed a 4-to 6-fold-higher risk of having cervical precancerous cytological lesions than did patients with single high viral loads. Compared to NILM, multiple infections, especially with multiple high viral loads, were significantly associated with cytological precancerous lesions. However, the presence of multiple infections did not distinguish low-grade from high-grade cytological lesions. Human papillomaviruses (HPV) are DNA viruses that infect cutaneous and mucosal epithelia. Until now, 120 HPV genotypes have been characterized based on sequence information (1), with evidence that even more exist (2). There are 51 mucosal HPV types that have been recognized, and these are further divided into three groups based on their epidemiological association with cervical cancer (CxCa): 14 high-risk HPV (Hr-HPV) types (HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68), 6 possibly high-risk HPV (pHr-HPV) types (HPV26, -53, -67, -70, -73, and -82), and 31 low-risk HPV (Lr-HPV) types (HPV6, (3, 4). Recently, HPV types HPV55 and HPV64 have been removed from the list of distinct HPV types, as they share 93% sequence homology to HPV44 and HPV34, respectively (5). By definition, these types are referred to as subtypes, as is also the...

The DNA load of six high-risk human papillomavirus types and its association with cervical lesions

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Prevalence, genotype profile and risk factors for multiple human papillomavirus cervical infection in unimmunized female adolescents in Goiânia, Brazil: a community-based study

“…The highest prevalence of single or co-infection with multiple HPV types has been found in sexually active adolescents, young women [3-7], and women with impaired immune responses [8]. …”

Significance of “Not Detected but Amplified” Results by Real-Time PCR Method for HPV DNA Detection

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