Background: Low-grade cervical lesions have a high percentage of clearance in young women, even if 71–82% of low-grade intraepithelial lesion/atypical squamous cells of undetermined significance (LSIL/ASCUS) reported a High-Risk Human Papillomavirus (HR-HPV) infection, which correlates with an increased risk of Cervical Intraepithelial Neoplasia (CIN)2+. The immunogenic effect of the anti-HPV vaccine appears to be significant. The aim of the study is to evaluate the effect, two years after the diagnosis, of the anti-HPV preventive vaccination on patients with low-grade cervical lesions. Methods: We collected clinical, colposcopic, histological, and virological data from patients aged 21–45 years who attended the colposcopy service of the department of Obsetrics and Gynecology of IRCCS Foundation Policlinico San Matteo, Pavia, Italy. In the 2005–2019 period and had a low-grade pap-smear. Results: We enrolled 422 women consecutively, divided into two groups (vaccinated and not vaccinated) for the retrospective analysis. The rate of persistence and progression of CIN were higher in the not-vaccinated group (p = 0.019). The relative risk (RR) to develop CIN2+ during follow-up vs. the the CIN1 persistence was 1.005 (95% Confidence Interval—CI 0.961–1.051) vs. 0.994 (95% CI 0.994–1.018) for age, 3.472 (95% CI 1.066–11.320) vs. 1.266 (95% CI 0.774–2.068) for non-vaccinated, 0.299 (95% CI 0.088–1.018) vs. 0.518 (95% CI 0.242–1.109) for HIV status negative, respectively. Analyzing the time to negativity, the odds ratio (OR) was 1.012 (95% CI 1–1.024) for age and 1.591 (95% CI 1.223–2.069) for vaccination; on the other hand, considering the relationship between the time to negative and the HPV genotypes contained in the 9-valent HPV vaccines, the OR was 1.299 (95% CI 1.026–1.646) for at least one of these at recruitment and 0.631 (95% CI 0.471–0.846) at follow-up. Furthermore, the presence of at least one of the HPV genotypes targeted by the HPV nonavalent vaccine is a key indicator of the risk of progression to CIN2+: OR was 3.443 (95% CI 1.065–11.189) for the presence of at least one HPV genotype at enrollment and 5.011 (95% CI 1.899–13.224) for the presence of at least one HPV genotype at follow-up, respectively. Conclusions: We reported in a retrospective study the benefit of anti-HPV vaccination in promoting negativity and increasing low-grade cervical lesions regression. Full article

Background: Women living with Human Immunodeficiency Virus are at higher risk of cervical cancer and precancer compared to women without HIV infection. The aim of the study is to evaluate the risk factors for the development of CIN2+ in a cohort of WLWH with negative colposcopy and cytology during a long follow-up period. Methods: We enrolled, in a multicentric retrospective cohort study, WLWH who attended the colposcopic services from 1999 to 2019. Patients with a normal Pap smear, a negative HR-HPV test, and at least one year of follow-up were considered for the anlysis. Results: The five-year cumulative incidence of histologically confirmed HSIL was 8.3% (95% CI = 2.6–13.6) among subjects with a CD4+ cell count of <200 cells/µL at any visit and 2.1% (95% CI = 0.7–3.4, p = 0.001) in women with a CD4+ cell count of persistently >200 cells/µL. In women with persistent HR-HPV infection, the five-year cumulative incidence of CIN 2+ was 6% (95% CI = 1.6–10.2) versus 2% (95% CI = 0.4–3.6, p = 0.012) in women without HPV infection. An HIV viremia of >200 copies/mL, a CD4+ cell count of <200 cells/µL, persistent HR-HPV infection, and smoking ≥10 cigarettes/day were all independent and statistically significant risk factors associated with the development of CIN2+ during follow-up. Conclusions: WLWH with good immune status and negative Pap smear and HR-HPV test have a low risk for CIN2+. Full article

We conducted a prospective, randomized two-arm, parallel group, and open label trial to investigate whether the use of LINE would increase HPV vaccine intention among not completely vaccinated university students. In June 2020, we recruited students aged between 18 and 35 years from four universities in Japan. Among the 357 enrollees (female, 53%), 178 and 179 participants were randomized into the LINE and Mail groups, respectively. At baseline, within three years, vaccine intention was observed in 40% vs. 42% of participants, respectively. At the first intervention, which provided similar PDF leaflets about HPV vaccine and cervical cancer prevention, there was no significant difference in vaccine intention between the two groups. However, at the second intervention of LINE-assisted knowledge intervention for 5 days per week for 7 weeks, the LINE group had a higher proportion of vaccine intention than the no intervention group (66% vs. 44%, OR: 2.62, 95% confidence interval (CI): 1.59–4.35) in per-protocol analysis. The significance remained in the intention-to-treat analysis of multiply imputed datasets. Although LINE did not directly increase HPV vaccine intention compared to conventional posts, the LINE-assisted provision of information was effective in improving HPV vaccine intention among Japanese university and college students. Full article

Identification of HPV infection is usually performed on cytological specimens, despite the often transient virus types. HPV profile analysis of pathologically confirmed lesions can also be performed on formalin-fixed paraffin-embedded (FFPE) cone samples and should be taken as standard during follow-up. We compared HPV profiles of cytological and FFPE specimens of women diagnosed with HSIL. Archived PAP smears and FFPE cones from 49 patients were processed. For genotyping, the HPV Direct Flow CHIP test was used. All samples were positive. HPV profile agreement of the two sample types was 84.16–100%. Mono-infections occurred in 12.24% and 61.22% in PAP smears and FFPE specimens, respectively; while multi-infections were detected in 87.76% and 38.78%, respectively. The most abundant genotypes were HPVs 16, 31, and 51/33. Of all infections, 56.25% and 64.93% were caused by nonavalent vaccinated type (VT) HPVs; while 50.69% and 38.96% belonged to non-nonavalent VT HPVs, in PAP smears and FFPE specimens, respectively. Our results confirmed the importance of HPV genotyping of FFPE cone samples. We also confirmed a remarkable presence of non-vaccinated HPV types in HSIL cases indicating the importance of vaccine development. Full article

The aim of this study was to design, develop, and evaluate the feasibility of a theory- and evidence-based intervention to improve human papillomavirus (HPV) and HPV vaccine knowledge and intention to vaccinate, among parent–daughter dyads. A theory- and evidence-based online behavioral intervention, “Is the HPV vaccine for me?”, was developed to improve HPV and HPV vaccine knowledge and intention to vaccinate. Knowledge, intention to vaccinate, and feasibility of the intervention were evaluated in a prospective, randomized, controlled feasibility trial. A total of 49 parent–daughter dyads completed the baseline knowledge assessment (n = 24 control, n = 25 intervention), and 35 dyads completed the knowledge assessment at week 2 (n = 17 control, n = 18 intervention). The intervention resulted in a statistically significant increase in HPV and HPV vaccine knowledge and intention to vaccinate. All intervention participants found the video interesting, while 96% found it useful. This intervention was found to be useful, effective, safe, and acceptable in this feasibility study. Full article

Objective: This study aimed to determine human papillomavirus (HPV)-related awareness and willingness to receive HPV vaccination among college students, in Wenzhou, and its associated factors. Methods: A cross-sectional epidemiological study was conducted among college students in Wenzhou to investigate their knowledge, attitude, and factors affecting their willingness to receive HPV vaccination. Results: A total of 1035 questionnaires were collected, of which 1002 were valid (males: 374, females: 628). In total, 904 (90.2%) college students had heard of HPV, with a lower rate among males than females (85.3% vs. 93.2%, p < 0.05) and 693 (69.2%) had heard of the HPV vaccine, with a significantly lower rate among males than females (53.7% vs. 78.3%, p < 0.05). Overall awareness of HPV and HPV vaccine among males and females was moderate, with lower awareness among males. A total of 55.9% of males and 80.4% of females indicated that they would be willing to receive the HPV vaccine, a significant difference (p < 0.001). The price, safety of HPV vaccine, and lack of knowledge about HPV and HPV vaccine were the major barriers to HPV vaccination for college students. Compared to females, inadequate knowledge of HPV was the main barrier factor for HPV vaccination among male college students. Conclusions: The overall knowledge level of males is lower than that of females. For male college students, providing more knowledge about HPV infection is helpful to promote their willingness to vaccinate. It is necessary to promote HPV-related knowledge for male and female college students, respectively. Full article

External anogenital warts (EGW) are primarily associated with the low-risk human papillomavirus (HPV) genotypes 6 and 11, though coinfection with other low-risk and oncogenic high-risk HPV genotypes also occurs. Although there have been many studies on HPV-associated disease, the prevalence of HPV genotypes associated with EGW is not well characterized. The objective of our retrospective study was to determine the prevalence of HPV genotypes among patients diagnosed with EGW in the south-west of Hungary. Archived formalin-fixed paraffin-embedded tissues from 94 patients were processed in our study. HPV genotypes were determined, applying HPV Direct Flow CHIP test. The overall prevalence of HPV DNA in the EGW samples was 100%, yielding 131 infections among the 94 samples. Of these cases, 72.3% were mono while 27.6% were multi-infections. Out of the 131 infections, the cumulative prevalence of HPV 6 and 11 was 71%. A total of 98.9% of the samples were carrying at least one of these genotypes, while 19.1% of the cases occurred with at least one high-risk genotype. Data from our study could provide invaluable information concerning the prevalence of HPV types among patients with EGW, enabling improved assessment of the actual and future efficacy of vaccination programs, vaccine development, and forecast changes in infection patterns. Full article

Human papillomavirus infection is a cause of the development of invasive cervical cancer. Three types of vaccine are currently available to prevent precancerous/cancerous lesions due to persistent infection, which is supported mainly by 7 different high-risk genotypes. The aim of this pilot study was to acquire preliminary data on type-specific prevalence 10 years after the implementation of the HPV vaccination program in Italy, in order to subsequently plan appropriate observational studies in the Italian population. First-voided urine samples were collected from 393 consenting subjects, both females and males, aged 18–40 years, and HPV DNA was detected by PCR amplification of a 450 bp L1 fragment. All amplified products were genotyped by means of the Restriction Fragment Length Polymorphism (RFLP) method. The female population was divided into three cohorts (“vaccine-eligible”, “pre-screening” and “screening” cohorts) according to the preventive intervention scheduled by age; males were included in the same three cohorts according to their year of birth. The overall prevalence of HPV infection was 19%, being higher in females than in males (22.1% vs. 13.6%, p = 0.03729). In the female population, 10 years after the start of the national immunization program, we observed a reduction in the prevalence of vaccine types and the number of circulating genotypes, especially in the “vaccine-eligible” cohort. The frequency of HPV vaccine types increased with age, particularly in males in the “pre-screening” and “screening” cohorts. Our study highlights the importance of monitoring HPV infection in both genders, to validate the effect of the HPV vaccination program. Full article

The human papillomavirus (HPV) can cause different cancers in both men and women. The virus interferes with functions of the cervix, vulva, vagina, anus in the anogenital area, breast, and head and neck cancer due to the local lesions. The tumors lead to death if not treated as a result of distant metastasis to internal organs and brain. Moreover, HPV attenuates the immune system during chronic infection and releases viral antigens into the tumor microenvironment. The tumors know how difficult is to win the battle with a strong united army of immune cells that are equipped with cytokines and enzymes. They confuse the immune cells with secreting viral antigens. The immune system is equipped with cytokines, a complement system, antibodies, and other secretory proteins to overcome the foreign invaders and viral antigens. However, the majority of the time, tumors win the battle without having all the equipment of the immune cells. Thus, in this review, we describe the recent progression in cellular and humoral immunity studies during the progression of HPV-related cancers. First of all, we describe the role of B, plasmoid cells, and B regulatory cells (Breg) in their functions in the tumor microenvironment. Then, different subtypes of T cells such as T CD8, CD4, T regulatory (Treg) cells were studied in recently published papers. Furthermore, NK cells and their role in tumor progression and prevention were studied. Finally, we indicate the breakthroughs in immunotherapy techniques for HPV-related cancers. Full article

(1) Background: Premature ovarian insufficiency (POI) has been linked to human papilloma virus (HPV) vaccination in small case-reports. The aim of this meta-analysis was to evaluate the risk of POI after HPV vaccination. (2) Methods: Electronic searches in MEDLINE Scopus, LILACS, ClinicalTrials.gov, EMBASE, PROSPERO, Cochrane CENTRAL and other registries were searched from inception to September 2022. Inclusion criteria were cohort studies of female children or adolescents vaccinated with quadrivalent (4vHPV), bivalent (2vHPV) or 9-valent (9vHPV) vaccine and compared to unvaccinated, other HPV vaccine, or vaccinated with other childhood vaccine girls. Primary outcome was risk of POI after vaccination. (3) Results: Four studies, including 1,253,758 patients, were included. Overall, there was no significant risk for POI between 4vHPV and controls (unvaccinated or other vaccines) (RR 0.47 (95% CI 0.14 to 1.59) I² = 75%), or unvaccinated only controls (RR 0.75 (95% CI 0.22 to 2.49) I² = 26%). One study reported a significant reduction of POI risk for 4vHPV relative to the other childhood vaccinations (RR 0.03 (95% CI 0.00 to 0.21)); meanwhile, one study showed no increased risk with 4vHPV relative to 2vHPV and 9vHPV (RR 0.93 (95% CI 0.33 to 2.64)). (4) Conclusions: 4vHPV vaccination does not seem to increase risk of POI relative to unvaccinated people or other childhood vaccines. No difference was seen with 4vHPV vaccine relative to 2vHPV and 9vHPV. Moreover, the risk of POI after HPV vaccination is relatable to worldwide incidence, giving reassurance about safety. Full article

Objective: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. Methods: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Results: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. Conclusions: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment. Full article