case report

Case Report: Co-Infection of Streptococcus Dysgalactiae Subspecies Equisimilis and HPV11 in Laryngeal Papilloma

Aastha Sobti1, Malin Lindstedt1, Fredrik Andersson2, Roland Rydell3, Ola Forslund4, 5*

1Department of Immunotechnology, Lund University, Lund, Sweden

2Department of Genetics and Pathology, Laboratory Medicine Region Skåne, Lund, Sweden

3Department of ORL, Head & Neck Surgery, Skåne University Hospital, Lund, Sweden

4Department of Laboratory Medicine, Lund University, Sweden

5Clinical Microbiology, Infection Prevention and Control, Office for Medical Services Region Skåne, Sweden

*Corresponding author: Ola Forslund, Department of Laboratory Medicine, Lund University and Clinical Microbiology, Infection Prevention and Control, Office for Medical Services Region Skåne, Sweden

Received Date: 08 October 2022

Accepted Date: 11 October 2022

Published Date: 14 October 2022

Citation: Sobti A, Lindstedt M, Andersson F, Rydell R, Forslund O (2022) Case Report: Co-Infection of Streptococcus Dysgalactiae Subspecies Equisimilis and HPV11 in Laryngeal Papilloma. Ann Case Report. 7: 993. DOI: https://doi.10.29011/2574-7754.100993


We report microbial and immune cell findings from a 59-year-old male with a history of recurrent HPV11-positive laryngeal papilloma (LP) for 48 years. During the years 2019 and 2020, surgery for LP was performed at frequency of 4.5 per year (9 times in 2 years). In March 2021 a swab sample was obtained from LP during surgery, and Streptococcus dysgalactiae subspecies equisimilis (SDSE, EMM type stG840) was isolated. The identical SDSE strain (stG840) and Hemophilus parahaemolyticus were detected in LP during the next surgery in August 2021. After both occasions (March and August 2021), antibiotic treatment for 10 days was prescribed, and the patient had two surgeries per year (every 6 months). Furthermore, Gram-positive cocci, likely SDSE, were scattered throughout superficial layers of a formalin-fixed-paraffinembedded LP-sample from January 2021. At surgery in February 2022, Streptococcus agalactiae (GBS) and Staphylococcus aureus were identified in a swab from the LP. Fresh biopsies were further analyzed over two years, where increased myeloid cells, neutrophils, and reduced cytotoxic T cells were observed by flow cytometry. Staining of LP tissue revealed cytotoxic T cells in the periphery and within vascular regions of the LP. An average of 47 (range 22-74) HPV11 DNA copies/cell among nine LP-samples was observed, whereas a paired healthy larynx tissue sample demonstrated 0.0013 HPV11 DNA copies/ cell as well as an increased proportion of cytotoxic T cells. In conclusion, the human pathogen SDSE was present in a case with a long history of LP. Antibiotic treatment coincided with fewer surgeries per year. Neutrophils were present in LP tissue, and cytotoxic T cells appeared to have limited infiltration capacity. HPV11 levels were stable during the patient’s clinical symptoms. Further research is needed to investigate a possible role of concomitant bacterial species in LP and if appropriate antibiotic treatment could reduce frequency of surgeries.


Laryngeal papillomatosis (LP) occurs in the larynx and sometimes extends to the nasopharynx and lungs, and when it recurs it is known as recurrent respiratory papillomatosis (RRP) [1]. Papilloma can occur in childhood (juvenile-onset RRP) as well as in adults (adult-onset RRP) and may lead to difficulty in breathing, hoarseness, and obstruction of the respiratory tract [2].

Management usually involves surgical interventions. Some adjuvant therapies, such as cidofovir, interferon, proton pump inhibitors, and therapeutic and prophylactic human papillomavirus 9-valent vaccines may, in some patients increase the time between surgeries [3].

LP is associated with low-risk human papillomavirus (HPV), especially types 6 and 11. HPV11 is the more aggressive of the two types and is usually associated with younger patients at the onset and a more detrimental course [4, 5]. There is also evidence that HPV is transmitted vertically from mother to firstborn and through oro-genital contact [6]. Despite the presence of HPV DNA in the larynx of 5% of the healthy population, only a small proportion develops RRP [7].

Interestingly, the exclusion of CD8 T cells may play a role in persistence of HPV in the cervix [8, 9]. Also, the presence of vaginal Peptostreptococcus anaerobius has been linked to cervical cancer progression by inducing macrophage polarization [10]. Some studies have investigated immune cells within the RRP [10-13]. The RRP lesions have been shown to have a suppressive microenvironment for T helper 1-like responses, thereby allowing for recurrent lesions [10]. An infiltration of T regulatory cells (CD4+/CD25+/Foxp3+/CD127+low) have also been observed [11]. Additionally, the severity of RRP has been linked with the presence of CD83+ dendritic cells in the epithelium [12] and an increased amount of neutrophils [13]. Although knowledge of the role of the microbiome among HPV-driven cancers is emerging [14-16], no such studies have been reported with context to laryngeal papilloma. Here we present a case with co-infection of HPV11 and pathogenic bacteria in recurrent LP, whose reduced frequency of surgery coincided with antibiotic intervention.

Figure 1: Time axis. (A) Bar graph showing the last 58 surgery dates and time to subsequent surgery (in days) over the years. (B) Depicts points of analysis and antibiotic treatments conducted since March 2020, as described in the case report.

Case Presentation

A 59-year-old male with recurrent LP has been treated since 1974 at the Department of Ear, Nose, and Throat Disease, Head and Neck Surgery, Region of Skåne, Sweden. The patient has undergone 135 anesthetic surgeries for HPV11-positive LP. On average, the patient returns to the clinic three to four times per year for surgical removal of the lesions, including COVID-19 pandemic in 2020 (Figure 1A). The patient had nonavalent HPV-vaccine (Gardasil) in February, April, and August of 2019.

Bacterial findings

Screening for bacterial species was conducted by collection of swabs (ESwab, Red Cap, and COPAN Cat No 482CE Copan Diagnostic Inc) from the papilloma and clinically healthy laryngeal mucosa in close vicinity to the papilloma, in March and August 2021 as well as February 2022 (Figure 1B). Samples were incubated and analyzed according to the standard protocol for lower airway bacterial diagnostics at Clinical Microbiology, Lund, Sweden. On both occasions in 2021, Streptococcus dysgalactiae subspecies equisimilis (SDSE) (EMM type stG480, Beta-streptococcus G) was isolated from the LP. No growth of any bacteria was noted from healthy laryngeal in March, whereas the SDSE was also isolated from healthy larynx as well as from a throat swab from August 2021. In addition, Hemophilus haemolyticus and Hemophilus parahaemolyticus were isolated from the LPs in March and August 2021, respectively. Furthermore, Grampositive cocci, likely SDSE, were found to be scattered throughout superficial layers of a formalin-fixed-paraffin-embedded (FFPE) LP sample from January 2021 (Figure 2). Thus, the cultivated SDSE strains from the two first occasions were identical whereas at the last visit in February 2022, when the patient had COVID-19, we isolated Streptococcus agalactiae (GBS) and Staphylococcus aureus from the LP. There was only growth of normal bacterial flora at the healthy laryngeal site and throat.