In this cohort of HIV-infected women, anal HPV infection was more prevalent and diverse than cervical HPV infection. Anal cytologic abnormalities were as prevalent as cervical cytologic abnormalities, and although abnormal cervical cytology was predictive of abnormal anal cytology, results were not highly concordant. These data support the need for studies of anal cytologic screening of HIV-infected women.

HPV detection was associated with CSA and increased with CSA certainty. In this population, genital HPV seemed to behave as a sexually transmitted infection.

The mechanisms underlying maternal tolerance of the semi-allogeneic fetus are not completely understood. The maternal immune system's response to the male antigen, H-Y is an example of the conflicting evidence that both supports and refutes the idea that the immune system in pregnant females is fundamentally different from that in non-pregnant females. Although multiple pregnancies may inactivate H-Y specific T cells, the immune system of the pregnant female can also generate a cytotoxic response to this antigen. To help understand this apparent conflict, we immunized female mice against H-Y with male spleen cells before pregnancy and examined the subsequent anti H-Y response during mid-pregnancy. The pregnant mice studied were able to mount cytotoxic immune responses to H-Y that were equivalent to those generated in their non-pregnant counterparts. Moreover the experience of pregnancy did not impair the ability to maintain immunologic memory to H-Y. The data support the idea that pregnancy does not violate general rules of antigen specific immunity, even if the antigen is expressed on the fetus.

Aberrant promoter methylation of biologically relevant genes in cervical cancer and uneven CpG distribution within the human papillomavirus 16 (HPV16) enhancer region have been reported. Cervical samples and questionnaires from 151 women screened for cervical cancer in Appalachian Ohio were analyzed. Methylation was measured by bisulfite sequencing in candidate gene sites in ESR1, DCC, p16, and LINE1 elements. Among 89 HPV16-positive women, CpG sites in the E6 promoter and enhancer regions and the L1 region of the HPV16 genome were measured. Methylation levels were compared by cervical cytology and HPV16 status. HPV methylation was low regardless of cytology status, however E6 methylation was significantly higher in women with normal cytology. ESR1 and DCC methylation were significantly higher in HPV16-positive women. Increased methylation at sites in the E6 promoter region was associated with lower odds of abnormal cytology. Increased methylation in candidate genes was associated with higher odds of abnormal cytology, particularly DCC region 2.4, DCC region 2.6, ESR1 region 3.2, and LINE1 site 1.2. HPV16 genome CpG methylation was low except for the L1 region. In general, lower HPV16 methylation and higher candidate gene methylation levels were associated with higher odds of abnormal cytology.

The performance of three line blot assays (LBAs), the Linear Array HPV genotyping assay (LA) (Roche Diagnostics), INNO-LiPA HPV Genotyping Extra (LiPA) (Innogenetics), and the reverse hybridization assay (RH) (Qiagen), was evaluated using quantitated whole genomic human papillomavirus (HPV) plasmids ( T he introduction of human papillomavirus (HPV) vaccines has highlighted the need for standardized accurate HPV genotyping assays to ensure comparability of results in laboratories worldwide, both before and after vaccine introduction. A large variety of assays, using both in-house methods and commercial kits, are available for HPV detection and typing (6), and more can be anticipated. International proficiency testing organized by the WHO HPV LabNet has documented significant differences in sensitivity, specificity, and reproducibility between different laboratories using a variety of testing platforms (2). Variation in performance for laboratories using the same assay implicates laboratory practice; however, the results also indicated differences between assays. The WHO HPV LabNet has further recognized the need for HPV typing assays that can easily be standardized, require minimal equipment for assay performance and interpretation, and can be used in a variety of laboratory settings. Following its meeting on the standardization of HPV assays and the role of the WHO HPV LabNet in supporting vaccine introduction (WHO, Geneva, Switzerland, 23 to 25 January 2008 [http://www.who.int/biologicals /publications/meetings/areas/vaccines/human_papillomavirus /HPV%20Jan%20meeting%20report_20080909%20_Clean _.pdf]), it was agreed that commercial assay kits should be evaluated in collaborative studies for proficiency.Reverse line blot assays (LBAs), based on consensus amplification of conserved regions of HPV followed by hybridization to type-specific probes on line blot strips, have been widely used. Available LBAs differ in the primer set (1, 3, 4) used in the amplification phase and in the number and sequences of the detection probes. Beyond thermocyclers for target amplifications, only temperature control water baths and visual inspection are required to carry out these assays. Therefore, the LBA platforms have the potential to meet the needs of the WHO for high-performance genotyping that does not involve expensive equipment.Studies have been conducted previously to compare and evaluate the performance of these HPV typing assays. Typically, these were restricted to DNA extracts from patient-collected anogenital specimens, which cannot be validated independently and limit the analysis to relative comparisons and assessments of type prevalence found by the individual assays (5,7,10). The use of plasmid standards offers clear advantages for more objective evaluations beyond that level. Cloned, full-length HPV genomic DNA (gDNA) provides complete control over genotype identity as well as copy number input and eliminates the need for a gold standard test.We selected three commercial LBAs using different primer sets and subjec...

In 2015, Botswana introduced the quadrivalent human papillomavirus (HPV) vaccine as a two-dose schedule in girls aged 9–13 years. We sought to establish a baseline HPV prevalence in unvaccinated young adults in Botswana. HIV-uninfected men and women aged 18–22 years were recruited from the University of Botswana in Gaborone during October 2019–February 2021. Demographic and behavioural characteristics were self-reported during structured interviews. Self-collected vaginal and penile swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared any HPV type, quadrivalent vaccine (HPV 6, 11, 16, 18)-type and non-quadrivalent vaccine-type prevalence in men and women and evaluated the risk factors for prevalence of any HPV type. A total of 493 men and 500 women were included in the analysis. Compared to men, women had higher prevalence of any HPV type (63.0% versus 31.4%, P < 0.001), vaccine-type HPV (21% versus 9.7%, P < 0.001) and non-vaccine-type HPV (60.4% versus 28.4%, P < 0.001). Higher prevalence of any HPV type in men and women was associated with having ≥2 sex partners in the past 12 months; always using condoms in the past 3 months was associated with a lower HPV prevalence. These data provide baseline information for future evaluation of the population impact of the HPV vaccination programme, including potential herd effects in men.

Introduction In 2015, Botswana introduced quadrivalent human papillomavirus (HPV) vaccine for girls aged 9–13 years. To establish a baseline HPV prevalence for future HPV vaccine impact monitoring, we evaluated HPV prevalences among the youngest unvaccinated women in Botswana and compared HPV prevalences among women living with HIV (WLHIV) and without HIV. Methods Women aged 18–22 years were recruited from the University of Botswana and HIV clinics in Gaborone from October 2019–January 2021. Demographic and behavioral characteristics were self-reported during structured interviews; HIV clinical characteristics were abstracted from medical charts. Self-collected vaginal swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared prevalence of any HPV, high risk (HR)-HPV, and quadrivalent HPV vaccine types (HPV6/11/16/18) among WLHIV and women without HIV and evaluated risk factors for prevalence of HR-HPV. Results A total of 306 WLHIV and 500 women without HIV were recruited. Compared to women without HIV, WLHIV were more likely to be sexually experienced (86.6% versus 74.4%) and have ≥ 3 lifetime sex partners (55.3% versus 27.8%). All HPV type prevalences were significantly higher among WLHIV compared to women without HIV, including prevalence of any HPV (82.7% versus 63.0%), HR-HPV (72.9% versus 53.8%), and quadrivalent vaccine HPV types (34.3% versus 21.0%). Among WLHIV, there were no differences between those perinatally and non-perinatally infected for HPV prevalences, number of HPV types detected, CD4 count, or viral load. Conclusions Over one-third of WLHIV and nearly a quarter of those without HIV had vaccine-type HPV detected. This study supports need for the national HPV vaccination program in Botswana and provides important baseline data for future evaluation of impact of the program.

It has been suggested that the maternal immune system favors noncytotoxic, "TH-2" immune responses in order to tolerate the developing fetus. In some strains of mice, pregnant females will reject a male skin graft, even as they tolerate their male fetuses. This rejection is based on responsiveness to the male antigen H-Y. In this study we test whether functional maternal tolerance of male fetuses is critically dependent on the TH-2 cytokine Interleukin 10 (IL-10). Normal and IL-10-deficient (10-KO) females were sensitized against H-Y by intraperitoneal injection of male spleen cells before mating with 10-KO males. Litters born to 10-KO females were of comparable size to those born to normal females of the same genetic background. The proportion of males per litter was not adversely affected by IL-10 deficiency. Taken together, our work and others suggest that IL-10 may not be critically important for maternal tolerance of the fetus and extends the evidence against the idea that successful mouse pregnancy depends on TH-2 deviation of the maternal immune system.