The high prevalence of STIs and the high incidence of HIV demonstrate the great vulnerability of these high-risk populations and indicate the urgent need for preventive strategies on intervention and facilitation of access to healthcare programs.

Objectives: High-risk types of human papillomavirus (HPV) are strongly associated with cervical cancer (CC), and Chlamydia trachomatis (CT), the most frequent sexually transmitted bacterial infection (STBI) worldwide, seems to be a risk factor for HPV infection and for CC. It is also known that both agents are more prevalent in vulnerable communities where lack of adequate primary health care is a cause for concern. The aim of this work was to determine the impact of CT and HPV infections in women belonging to an isolated aboriginal population (Pilaga community) from a poor region in Northern Argentina (province of Formosa). For this purpose, a cross-sectional study was performed in all sexually active Pilaga women, who attended a local community-based gynecological health screening project. The polymerase chain reaction (PCR) method on a cervical brush specimen was used to detect both agents. Results: A total of 227 women (20% of the total female population of the Pilaga community) were studied and the overall prevalence was 26.4% for CT, 46.7% for HPV and 16.3% for concurrent infection. CT infection was higher in HPV DNA positive (34.2%) than in HPV DNA negative women (19%; OR: 2.22/95% CI = 1.16-4.28 / p = 0.009) and the most prevalent HPV types were HPV-16 (19.4%), 6 and 18 (5.3%), 58 (3.5%) and 33 (3.1%). Conclusions:The prevalence of CT and HPV observed in Pilaga women are among the worst registered in Latin America. Also, data collected suggest that chlamydial infection may play an important role in the natural history of HPV infection. On this respect, we propose that the association between these two agents seems to be more related to a mutual potentiation than to the fact that they share a common route of transmission.

The proportion of HPV16 and 18-associated cervical cancer (CC) appears rather constant worldwide (≥70%), but the relative importance of the other HR-HPV differs slightly by geographical region. Here, we studied the HPV genotype distribution of HPV positive Latin American (LA) women by histological grade, in a sub-cohort from the ESTAMPA study; we also explored the association of age-specific HPV genotypes in severe lesions. Cervical samples from 1,252 participants (854 ≤CIN1, 121 CIN2, 194 CIN3 and 83 CC) were genotyped by two PCRs-Reverse Blotting Hybridization strategies: i) Broad-Spectrum General Primers 5+/6+ and ii) PGMY9/11 PCRs. HPV16 was the most frequently found genotype in all histological grades, and increased with the severity of lesions from 14.5% in ≤ CIN1, 19.8% in CIN2, 51.5% in CIN3 to 65.1% in CC (p < 0.001). For the remaining HR-HPVs their frequency in CC did not increase when compared to less severe categories. The nonavalent vaccine HR-types ranked at the top in CC, the dominant ones being HPV16 and HPV45. HR-HPV single infection occurs, respectively, in 57.1% and 57.0% of ≤CIN1 and CIN2, increasing to 72.2% and 91.6% in CIN3 and CC (p<0.001). No association between age and HPV type was observed in CC, although the risk of HPV16 infection in CIN3 cases increased with age. Results confirm the relevance of HPV16 in the whole clinical spectrum, with a strong rise of its proportion in CIN3 and cancer. This information will be relevant in evaluating the impact of HPV vaccination, as a baseline against which to compare genotype changes in HPV type-specific distribution as vaccinated women participate in screening in LA region. Likewise, these data may help select the best HPV testing system for HPV-based efficient, affordable, and sustainable screening programmes.

The incidence of cervical cancer in Paraguay is among the highest in the world. This study aimed to determine the distribution of human papillomavirus (HPV) genotypes in Paraguayan women, according to the severity of the cervical lesion. This cross-sectional study included 207 women without a squamous intraepithelial lesion, 164 with low-grade squamous intraepithelial lesions, 74 with high-grade squamous intraepithelial lesions, and 41 with cervical cancer. Type-specific HPV was determined by the polymerase chain reaction with MY9/11 L1 and GP5+/GP6+ L1 primers, followed by restriction fragment length polymorphism and reverse line blotting hybridization, respectively. In total, 12 high-risk and 24 low-risk HPVs types were detected. HPV 16 was the most prevalent, followed by HPV 18 in cervical cancer (14.6%), HPV 31 in high-grade squamous intraepithelial lesions (14.9%), HPVs 58/42 in low-grade squamous intraepithelial lesions (9.1% each), and HPVs 31/58 (2.4% each) in women without squamous intraepithelial lesions. Among 285 positive samples, 24.2% harbored multiple HPV types, being this more prevalent in women with squamous intraepithelial lesions (30.8% in low-grade squamous intraepithelial lesions, 22.5% in high-grade squamous intraepithelial lesions, and 22.0% in cervical cancer) than in women without lesions (9.3%). The higher prevalence of HPV 16 and other high-risk HPVs in women both with and without cervical lesions may explain the high incidence of cervical cancer in Paraguay. This information may be of importance for local decision makers to improve prevention strategies. In addition, these results may be useful as baseline pre-vaccination data for a future virological surveillance in Paraguay.

The prevalence of CT and HPV observed in Pilaga women are among the worst registered in Latin America. Also, data collected suggest that chlamydial infection may play an important role in the natural history of HPV infection. On this respect, we propose that the association between these two agents seems to be more related to a mutual potentiation than to the fact that they share a common route of transmission.

A large variety of HPV genotypes was detected and showed a slightly different pattern from previous studies on urban women in Paraguay, with the predominance of HR-HPV. Furthermore, the information of co-infections involved in BV could be useful for the improvement of national prevention programs, as well as for laboratory surveillance of these genital infections.

Highlights High-risk HPV infection is less frequently detected in HIV-positive non-metastatic ASCC compared with HIV-negative cases. Mutational profile identified in the non-metastatic ASCC cohort revealed expected similarities with metastatic ASCC. High PD-L1 expression levels are associated with high CD3 and CD8 TIL density, complete response to treatment, and good survival outcome of ASCC patients. PD-L1 is a reliable predictive and prognostic biomarker that allows the stratification in low- vs. high-risk ASCC patients at their initial therapeutic approach.

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