Human papillomavirus type distribution in cervical cancer in Indiana and Botswana

Indiana University-Purdue University Indianapolis (IUPUI)In this study we compared the distribution of HPV types in cervical cancer specimens from women living in either Indiana or Botswana. Paraffin-embedded blocks of formalin-fixed cervical cancer specimens were identified from women living in Indiana (n=51) or Botswana (n=171

Development of a SimpleProbe real-Time PCR Assay for rapid detection and identification of the US novel urethrotropic clade of Neisseria meningitidis ST-11 (US_NmUC)

Urethritis, or inflammation of the urethra, is one of the most common reasons men seek clinical care. Sexually transmitted pathogens including Neisseria gonorrhoeae are responsible for over half of the symptomatic urethritis cases in U.S. men. Recently, clinics in Indianapolis, Columbus, Atlanta, and other U.S. cities began to note increasing numbers of men presenting with urethritis and Gram-negative intracellular diplococci in their urethral smears who test negative for N. gonorrhoeae. Many of these discordant cases, which have periodically reached highs of more than 25% of presumed gonococcal cases in some sexually transmitted infection clinics in the U.S. Midwest, are infected with strains in a novel urethrotropic clade of Neisseria meningitidis ST-11 (US_NmUC). However, no cultivation-independent tests are available for the US_NmUC strains, and prior studies relied on microbial culture and genome sequencing to identify them. Here, we describe a PCR test that can identify the US_NmUC strains and distinguish them from commensal and invasive N. meningitidis strains as well as N. gonorrhoeae. Our SimpleProbe®-based real-time PCR assay targets a conserved nucleotide substitution in a horizontally acquired region of US_NmUC strain genomes. We applied the assay to 241 urine specimens whose microbial compositions had previously been determined by deep shotgun metagenomic sequencing. The assay detected the single US_NmUC positive case in this cohort, with no false positives. Overall, our simple and readily adaptable assay could facilitate investigation of the pathogenesis and epidemiology of the US_NmUC clade

Redetection of human papillomavirus type 16 infections of the cervix in mid-adult life

Purpose: To assess whether HPV 16 originally detected in adolescent women can be redetected in adulthood. Methods: A convenience sample of 27 adult women with known HPV 16 detection during adolescence was assessed for HPV 16 redetection. A comparison of the long control region (LCR) DNA sequences was performed on some of the original and redetected HPV 16 isolates. Results: Median age at reenrollment was 27.5 years (interquartile range of 26.7–29.6). Reenrollment occurred six years on average after the original HPV 16 detection. Eleven of 27 women had HPV 16 redetected. Some of these HPV 16 infections had apparently cleared during adolescence. LCR sequencing was successful in paired isolates from 6 women; in 5 of 6 cases the redetected HPV 16 isolates were identical to those detected during adolescence, Conclusions: HPV 16 may be episodically detected in young women, even over long time periods. HPV 16 redetection with identical LCR sequences suggests low-level persistent infection rather than true clearance, although newly acquired infection with an identical HPV 16 isolate cannot be excluded. However, this study suggests that a new HPV 16-positive test in a clinical setting may not indicate a new infection. Keywords: Human papillomavirus (HPV), Redetection, Latency, Long control region, Sequencin

Invasive cervical cancers in the United States, Botswana and Kenya: HPV type distribution and health policy implications

Abstract Background More deaths occur in African women from invasive cervical cancer (ICC) than from any other malignancy. ICC is caused by infection with oncogenic types of human papillomavirus (HPV). Co-infection with the human immunodeficiency virus (HIV) accelerates the natural history of ICC, and may influence the HPV type distribution. Because HPV vaccines are available, this malignancy is theoretically preventable, but the vaccines are largely type-specific in protection against infection. Data on specific HPV types causing ICC in African women is limited, and many studies utilized swab samples rather than actual cancer tissue. A previous study using archived, ICC tissue from women in Botswana identified an unusual HPV type distribution. A similar study was therefore performed in a second sub-Saharan country to provide additional information on the HPV type distribution in ICC. Methods Archived, formalin-fixed, paraffin-embedded ICCs were acquired from women in the United States, Kenya, or Botswana. DNA was extracted and HPV genotyping performed by Roche Linear Array. HIV sequences were identified in ICCs by PCR. Results HPV types 16 or 18 (HPV 16/18) were identified in 93.5 % of HPV-positive ICCs from the U.S., 93.8 % from Kenya, and 61.8 % from Botswana (p < 0.0001). Non-HPV 16/18 types were detected in 10.9 % of HPV-positive cancers from the U.S., 17.2 % from Kenya, and 47.8 % from Botswana (p < 0.0001). HIV was detected in 2.2, 31.5, and 32.4 % from ICCs from the U.S., Kenya, or Botswana, respectively (p = 0.0002). The distribution of HPV types was not significantly different between HIVinfected or HIV-uninfected women. The percentages of ICCs theoretically covered by the bivalent/quadrivalent HPV vaccines were 93.5, 93.9, and 61.8 % from the U.S., Kenya and Botswana, respectively, and increased to 100, 98, and 77.8 % for the nanovalent vaccine. Conclusions HPV 16/18 caused most ICCs from the U.S. and western Kenya. Fewer ICCs contained HPV 16/18 in Botswana. HIV co-infection did not influence the HPV type distribution in ICCs from African women from the two countries. Available HPV vaccines should provide protection against most ICCs in the U.S. and Kenya. The recently developed nanovalent vaccine may be more suitable for countries where non-HPV 16/18 types are frequently detected in ICC