Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women

Purpose Cervical squamous cell carcinoma (SCC) continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common female cancer but also the leading cause of cancer-related deaths in women. Malawi, in particular, has the highest burden of cervical cancer. With the increasing use of human papillomavirus (HPV) vaccination, documenting the prevalent HPV types in those high-risk populations is necessary to both manage expectations of HPV vaccination and guide future vaccine development. Materials and Methods In this study, we performed HPV typing on 474 cervical SCC samples and analyzed the potential impact of HPV vaccination in this population. Results Ninety-seven percent of tumors were positive for at least one HPV type, and 54% harbored more than one HPV type. HPV 16 was the most common type (82%), followed by HPV 18 (34%), HPV 35 (24%), and HPV 31 (12%). A vaccine against HPV 16 and 18 would ideally prevent 53% of cervical SCC, and the nonavalent HPV vaccine (covering HPV 16, 18, 31, 33, 45, 52, and 58) would prevent 71% of cervical SCC in Malawi (assuming 100% vaccine efficacy). The main reason for a lack of coverage was high prevalence of HPV 35, which was also present as a single infection in a small subset of patients. Conclusion Although any HPV vaccination in this population would likely prevent a significant proportion of cervical cancer, the nonavalent vaccine would provide better coverage. Furthermore, investigation of the role of HPV 35 in this population, including possible cross-protection with other HPV types, should be pursued.

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Human Papillomavirus Typing of Rare Cervical Carcinomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-553-hptorc ◽

2004 ◽

Vol 128 (5) ◽

pp. 553-556

Author(s):

Janice Matthews-Greer ◽

Hugo Dominguez-Malagon ◽

Guillermo A. Herrera ◽

James Unger ◽

José Chanona-Vilchis ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Squamous Cell ◽

Vaccine Development ◽

Hpv 16 ◽

Cervical Carcinomas ◽

Rare Tumors ◽

Significant Difference ◽

Hpv Types

Abstract Context.—Most cervical tumors are classified as squamous cell carcinoma or adenocarcinoma, both of which are associated with persistent human papillomavirus (HPV) infection. Although other (rare) types represent less than 5% of all cervical carcinomas, it is necessary that these more unusual tumors be studied in the current era of papillomavirus vaccine development, especially in regions with high incidence of cervical cancer. Objective.—To compare papillomavirus types found in histologically rare cervical carcinomas (n = 29) with those types found in common cervical carcinomas (n = 14) archived at the Institute of Cancer in Mexico City, Mexico. Design.—Paraffin-embedded tissues were received and sectioned at the Louisiana State University Health Sciences Center at Shreveport. One section for each block was stained and examined by 2 pathologists. Specific histologies were categorized into 2 broad groups: common (squamous cell carcinoma or adenocarcinoma) or rare (adenosquamous, papillary, villoglandular, anaplastic, transitional, spindle, adenoid basal, colloid, neuroendocrine, and glassy cell carcinomas). Papillomavirus typing results were based on Roche Molecular Systems line-blot assay. Results.—No significant difference was found for dual HPV types (21% of both groups), positivity for HPV-16 (66% of rare tumors and 71% of common tumors), or absence of HPV types 16 or 18, although the rare cancers had a greater tendency toward more unusual HPV types (8/29 rare tumors and 1/14 common tumors had no HPV- 16 or HPV-18 DNA). Non–HPV-16/18 types found only in rare tumors included HPV types 52, 84, 26, 35, and 58. Conclusions.—Rare types of cervical carcinoma also are associated with papillomavirus, most with types similar to those found in common cervical neoplasias.

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Stakeholders’ Understandings of Human Papillomavirus (HPV) Vaccination in Sub-Saharan Africa: A Rapid Qualitative Systematic Review

Vaccines ◽

10.3390/vaccines9050496 ◽

2021 ◽

Vol 9 (5) ◽

pp. 496

Author(s):

Caroline Deignan ◽

Alison Swartz ◽

Sara Cooper ◽

Christopher J. Colvin

Keyword(s):

Systematic Review ◽

Cervical Cancer ◽

Human Papillomavirus ◽

Hpv Vaccine ◽

Hpv Vaccination ◽

Sub Saharan Africa ◽

African Countries ◽

Qualitative Systematic Review ◽

Sub Saharan ◽

And Gender

Cervical cancer rates in Sub-Saharan Africa (SSA) are amongst the highest worldwide. All three of the Human Papillomavirus (HPV) vaccines (9-valent, quadrivalent and bivalent HPV vaccine) provide primary protection against the most common cancer-causing strains of HPV (types 16 and 18) that are known to cause 70% of cervical cancers. Over the last five years, there has been an increase in Sub-Saharan African countries that have introduced the HPV vaccine. The majority of research has been conducted on supply-side barriers and facilitators to HPV vaccination uptake in SSA, yet little research has been conducted on demand-side or end-user perspectives of, and decisions around, HPV vaccination. In order to complement existing research, and inform current and future HPV vaccination implementation approaches, this qualitative systematic review explored Stakeholders’ understandings of HPV vaccination in SSA. This review searched the following databases: Embase (via Scopus), Scopus, MEDLINE (via PubMed), PubMed, EBSCOhost, Academic Search Premier, Africa-Wide Information, CINAHL, PsycARTICLES, PsycINFO, SocINDEX, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) and found a total of 259 articles. Thirty-one studies were found eligible for inclusion and were analyzed thematically using Braun and Clarke’s methods for conducting a thematic analysis. The quality of included studies was assessed using the Critical Appraisal Skills Programme (CASP) checklist. Three major themes emerged from this analysis; knowledge of HPV vaccination and cervical cancer is intertwined with misinformation; fear has shaped contradictory perceptions about HPV vaccination and gender dynamics are relevant in how stakeholders understand HPV vaccination in SSA.

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Human papillomavirus vaccination: evidence base for efficacy and safety

GYNECOLOGY ◽

10.26442/20795696.2021.2.200742 ◽

2021 ◽

Vol 23 (2) ◽

pp. 125-130

Author(s):

Yuliya E. Dobrokhotova ◽

Ekaterina I. Borovkova

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Hpv Vaccination ◽

Intraepithelial Neoplasia ◽

Evidence Base ◽

Hpv Infection ◽

Efficacy And Safety ◽

Human Papillomavirus Vaccination ◽

Hpv Types ◽

Further Development

The article provides a literature review on the prevention of cervical cancer by human papillomavirus (HPV) vaccination. Currently, 3 vaccines are available: the 4-valent vaccine against HPV types 6, 11, 16 and 18, the 9-valent vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 and the bivalent vaccine against HPV types 16 and 18. Vaccination provides protection for women and men against infection with HPV and further development of HPV-associated diseases. Following immunization, seroconversion develops in 93-100% of women and in 99-100% of men and is effective in preventing incident and persistent HPV infection as well as cervical intraepithelial neoplasia. HPV immunization is ineffective in treating an existing HPV infection, genital warts, or anogenital intraepithelial neoplasia. HPV vaccination status does not affect recommendations for cervical cancer screening.

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Population Impact of Girls-Only Human Papillomavirus 16/18 Vaccination in The Netherlands: Cross-Protective and Second-Order Herd Effects

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1770 ◽

2020 ◽

Author(s):

Joske Hoes ◽

Petra J Woestenberg ◽

Johannes A Bogaards ◽

Audrey J King ◽

Hester E de Melker ◽

...

Keyword(s):

Human Papillomavirus ◽

The Netherlands ◽

Hpv Vaccination ◽

Population Level ◽

Second Order ◽

Vaccine Uptake ◽

Heterosexual Men ◽

Hpv 16 ◽

Vaccination Programs ◽

Hpv Types

Abstract Background Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage. Methods We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. Results A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year [95% confidence interval {CI}, 10.6–14.5]), heterosexual men (13.0% per year [95% CI, 8.3–17.5]), and unvaccinated women (5.4% per year [95% CI, 2.9–7.8]). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women). Conclusions Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.

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Association of detection of aflatoxin in plasma of Kenyan women with increased detection of oncogenic HPV.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5530 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5530-5530

Author(s):

Jianjun Zhiang ◽

Elkanah Omenge ◽

Titus Maina ◽

Kapten Muthoka ◽

Stephen Kiptoo ◽

...

Keyword(s):

Cervical Cancer ◽

Cervical Dysplasia ◽

Hpv Infection ◽

Immunosuppressive Agent ◽

Sub Saharan Africa ◽

Hpv Testing ◽

Hpv 16 ◽

Kenyan Women ◽

Hpv Types ◽

Oncogenic Hpv

5530 Background: Cervical cancer is the leading cause of cancer-related deaths among women living in Africa. Only a small proportion of HPV-infected women develop cervical cancer and other cofactors may increase a woman’s risk of developing cervical cancer. Aflatoxin, a potent carcinogen and immunosuppressive agent, is produced by fungi that contaminate corn and other staple foods in sub-Saharan Africa. Women who ingest aflatoxin may be more likely to have persistent infections with oncogenic HPV type. Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from HIV-uninfected women 18 and 45 years of age who presented for cervical cancer screening at Moi Referral and Teaching Hospital (Eldoret, Kenya) and had normal VIA examination. HPV testing was performed on cervical swabs using the Roche Linear Array Assay. Aflatoxin-albumin adduct (AFB1-lys) was detected and quantified in plasma. The association of plasma AFB1-lys detection and concentration and the detection of HPV was examined. Results: Sufficient plasma was available from 88 HIV-uninfected women and was transported to the U.S. for aflatoxin testing. Valid HPV testing results were available for 86 of these women (mean age 34.0 years); 49 women (57.0%) had detectable AFB1-lys and 37 (43.0%) had no detection. Substantial variation existed in plasma AFB1-lys concentrations among the 49 women (range 0.02 to 0.21 pg/µL). Detection of AFB1-lys was not associated with age, and other behavioral factors such as number of lifetime partners, marital status and age at first sex. AFB1-lys detection was associated with detection of A9 HPV types (HPV 16, 31, 33, 35, 52, and 58) as a group in cervical swabs (p = 0.029) as well as A9 types excluding HPV 16 (p = 0.020), but not with individual A9 types, A7 HPV types (such as HPV 18), or low-risk HPV types. A concentration dependent association of AFB1-lys was seen with detection of A9 HPV types as a group (p = 0.009), non-HPV 16 A9 types (p = 0.005), and HPV 52 (p = 0.042), but not with the A7 HPV types. Conclusions: AFB1-lys was detected in 57% of HIV-uninfected Kenyan women without cervical dysplasia. AFB1-lys-positive women were more likely than AFB1-lys-negative women to have oncogenic HPV A9 types detected. Higher plasma AFB1-lys concentrations were associated with increased likelihood of oncogenic HPV A9 type detection. Further studies are needed to determine if chronic exposure to aflatoxin interacts with HPV infection (and possibly HIV co-infection) to modulate the risk of cervical cancer in women in Kenya and other developing countries.

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Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.2.610 ◽

1997 ◽

Vol 15 (2) ◽

pp. 610-619 ◽

Cited By ~ 27

Author(s):

P Viladiu ◽

F X Bosch ◽

X Castellsagué ◽

N Muñoz ◽

J M Escribà ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Prognostic Factor ◽

Squamous Cell ◽

Tumor Recurrence ◽

Human Papillomaviruses ◽

Enzyme Linked Immunosorbent Assay ◽

Hpv 16 ◽

Hpv Dna

PURPOSE To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

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Vaccines for cervical cancer

Epidemiology and Infection ◽

10.1017/s0950268805005728 ◽

2006 ◽

Vol 134 (1) ◽

pp. 1-12 ◽

Cited By ~ 22

Author(s):

C. M. LOWNDES

Keyword(s):

Cervical Cancer ◽

Pap Smear ◽

Invasive Cervical Cancer ◽

Significant Proportion ◽

Phase Iii ◽

Effective Vaccine ◽

Hpv 16 ◽

Pap Screening ◽

Hpv Types ◽

Cancerous Lesions

SUMMARYThis review focuses on current and future prevention of invasive cervical cancer (ICC), the second most common cancer among women worldwide. Implementation of population-based cytological screening programmes, using the ‘Pap’ smear to detect pre-cancerous lesions in the cervix, has resulted in substantial declines in mortality and morbidity from ICC in North America and some European countries. However, cases of, and deaths from, ICC continue to occur. Primary prevention of infection with high-risk human papillomavirus (HPV) types, the central causal factor of ICC, could further reduce incidence of and mortality from ICC. This is particularly the case in developing countries, which bear 80% of the burden of ICC, and where effective Pap screening programmes are extremely difficult to implement. Very promising results from several trials of synthetic HPV type-specific monovalent (HPV 16) and bivalent (HPV 16 and 18) vaccines have recently been published, showing high efficacy against type-specific persistent HPV infection and development of type-specific pre-cancerous lesions. Large-scale phase III trials of a number of such vaccine candidates are currently underway, and there is real hope that an effective vaccine capable of protecting against infection with HPV types 16 and 18 (which together account for ∼70% of cervical cancer cases worldwide), and thereby of preventing development of a very significant proportion of cases of ICC, could be available within the next 2 years.

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Acquisition, prevalence and clearance of type-specific human papillomavirus infections in young sexually active Indian women: A community-based multicentric cohort study

PLoS ONE ◽

10.1371/journal.pone.0244242 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244242

Author(s):

Richard Muwonge ◽

Partha Basu ◽

Tarik Gheit ◽

Devasena Anantharaman ◽

Yogesh Verma ◽

...

Keyword(s):

Human Papillomavirus ◽

Hpv Vaccination ◽

Hpv Infection ◽

Sample Collection ◽

Community Based ◽

Hpv 16 ◽

Indian Women ◽

Cervical Sample ◽

Hpv Prevalence ◽

Hpv Types

In context of the ongoing multi-centric HPV vaccine study in India, unvaccinated married women (N = 1484) aged 18–23 years were recruited in 2012–2015 as age-matched controls to the vaccinated women and followed up yearly. We assess type-specific prevalence, natural history and potential determinants of human papillomavirus (HPV) infection in these unvaccinated women. Cervical samples were collected yearly for at least four consecutive years. A Multiplex Type-Specific E7-Based polymerase chain reaction assay was used to detect 21 HPV types. HPV prevalence was 36.4% during 6 years. Most common HPV types were 16 (6.5%) and 31 (6.1%). Highest persistence were observed for HPV 35 (62.5%) and 52 (25%). New HPV acquisition rate was 5.6/1000 person-months of observation (PMO), highest for HPV 16 (1.1/1000 PMO). Type-specific clearance rates ranged between 2.9–5.5/100 PMO. HPV 16 and/or 18 infections were 41% (95% CI 4–63%) lower among women with 2-<3 years between marriage and first cervical sample collection compared to those with <2 years. HPV prevalence and acquisition rates in young Indian women were lower than their Western counterparts. HPV 16 infections being most common shows the importance and potential impact of HPV vaccination in India. Women with 2–3 years exposure had reduced risk possibly due to higher infections clearance.

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Human Papillomavirus Detection in Head and Neck Squamous Cell Carcinomas at a Tertiary Hospital in Sub-Saharan Africa

The Scientific World JOURNAL ◽

10.1155/2019/2561530 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Evans Aboagye ◽

Francis Agyemang-Yeboah ◽

Babatunde Moses Duduyemi ◽

Christian Obirikorang

Keyword(s):

Human Papillomavirus ◽

Oral Cavity ◽

Head And Neck ◽

Squamous Cell ◽

Tertiary Hospital ◽

Sub Saharan Africa ◽

Cross Sectional ◽

Hpv 16 ◽

Sub Saharan ◽

Oral Cavity Cancers

Fewer studies have been done over the years to establish the association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSSC) within the subregions of sub-Saharan Africa, and thus this study was designed to investigate the presence of HPV in HNSCC at a tertiary hospital in Ghana, providing additional evidence on the need to explore similar studies in other subregions. A retrospective cross-sectional study was employed to investigate the presence of the DNA of HPV genotypes in HNSCC archived tissue. A total of 100 HNSCC cases were classified as suitable for HPV genotyping. HPV-DNA was detected in 18% of the HNSCC cases, with 17 being HPV-16 and 1 dual infection with HPV-16 and HPV-18. HPV was prevalent in 50% of oropharyngeal cancers, 27% of laryngeal cancers, and 23% of oral cavity cancers. HPV E6/E7 oncogenic DNA was found in 18% of the HNSCC cases, with HPV-16 being the predominant genotype present. The pattern of HPV association was similar to earlier reported studies, recording a higher prevalence in oropharyngeal cancers, followed by laryngeal cancers and oral cavity cancers.

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Cohort profile: indigenous human papillomavirus and oropharyngeal squamous cell carcinoma study - a prospective longitudinal cohort

BMJ Open ◽

10.1136/bmjopen-2020-046928 ◽

2021 ◽

Vol 11 (6) ◽

pp. e046928

Author(s):

Lisa M Jamieson ◽

Gail Garvey ◽

Joanne Hedges ◽

Cathy Leane ◽

Isaac Hill ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Hpv Vaccination ◽

Hpv Infection ◽

Indigenous Australians ◽

Health State ◽

Hpv 16 ◽

Oral Hpv ◽

Hpv Types

PurposeOur aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma (OPSCC)-related HPV types (HPV 16 or 18); (3) develop HPV-related health state valuations and; (4) determine the impact on OPSCC and cervical cancers, and the cost-effectiveness of extending publicly-funded HPV vaccination among Indigenous Australians.ParticipantsParticipants were recruited from February 2018 to January 2019. Twelve-month follow-up occurred from March 2019 to March 2020. Participants provided socio-demographic characteristics, health-related behaviours including tobacco and alcohol use and sexual history. Health state preferences in regard to HPV vaccination, knowledge regarding HPV infection, OPSCC and cervical cancer were collected using a two-stage standard gamble approach. Participants provided saliva samples and DNA for microbial genotyping was extracted.Findings to dateOf the 910 participants who were positive for β-globin at baseline, 35% had any oral HPV infection. The most prevalent HPV types were 13 or 32 (Heck’s disease; 23%). The second most prevalent types were associated with OPSCC (HPV 16 or 18; 3.3%). Of the 645 participants who were positive for β-globin at 12-month follow-up, 43% had any HPV infection. Of these, 33% were HPV types 13 or 32 and 2.5% were HPV 16 or 18. Some 588 participants had β-globin positive oral samples at baseline and 12-month follow-up. The prevalence of any oral HPV infection increased from 34% at baseline to 44% at 12-month follow-up; due to increases in HPV types 13 or 32 (20% at baseline and 34% at 12-month follow-up).Future plansFurther funding will be sought to continue follow-up of this cohort, and to include (after a full medical history) a thorough clinical examination of the external head and neck; a complete oral examination and examination of the oropharynx. Blood tests for early stage OPSCC will also be undertaken.

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