ArticlePDF Available

The Ability of Two Chlorine Dioxide Chemistries to Inactivate Human Papillomavirus‐contaminated Endocavitary Ultrasound Probes and Nasendoscopes

Authors:
Article

The Ability of Two Chlorine Dioxide Chemistries to Inactivate Human Papillomavirus‐contaminated Endocavitary Ultrasound Probes and Nasendoscopes

Abstract

Sexual transmission is the most common pathway for the spread of Human papillomavirus (HPV). However, the potential for iatrogenic HPV infections is also real. Even though cleared by the Food and Drug Administration and recommended by the World Federation for Ultrasound in Medicine and Biology, several disinfectants including glutaraldehyde and o‐phthalaldehyde have shown a lack of efficacy for inactivating HPV. Other methods such as ultraviolet C and concentrated hydrogen peroxide have been shown highly effective at inactivating infectious HPV. In this study, two chlorine dioxide systems are also shown to be highly efficacious at inactivating HPV. An important difference in these present studies is that as opposed to testing in suspension or using a carrier, we dried the infectious virus directly onto endocavitary ultrasound probes and nasendoscopes, therefore, validating a more realistic system to demonstrate disinfectant efficacy. Highlights • Nonsexual transmission of Human Papillomavirus (HPV) is a real potential risk. For the first time, two chlorine dioxide chemistries are tested and shown to be efficacious in killing HPV. This study tested drying the infectious virus directly onto endocavitary ultrasound probes and nasendoscopes, therefore validating a more realistic system to demonstrate disinfectant efficacy.
© 2020 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc.
J Med Virol. 2020;15. wileyonlinelibrary.com/journal/jmv
|
1
Received: 6 November 2019
|
Accepted: 7 January 2020
DOI: 10.1002/jmv.25666
RESEARCH ARTICLE
The ability of two chlorine dioxide chemistries to inactivate
human papillomaviruscontaminated endocavitary
ultrasound probes and nasendoscopes
Craig Meyers
1
|
Janice Milici
1
|
Richard Robison
2
1
Department of Microbiology and
Immunology, Pennsylvania State College of
Medicine, Hershey, Pennsylvania
2
Department of Microbiology and Molecular
Biology, Brigham Young University, Provo,
Utah
Correspondence
Craig Meyers, Department of Microbiology
and Immunology, Pennsylvania State College
of Medicine, Hershey, PA 17036.
Email: cmeyers@pennstatehealth.psu.edu
Funding information
Tristel Solutions Limited, UK
Abstract
Sexual transmission is the most common pathway for the spread of Human
papillomavirus (HPV). However, the potential for iatrogenic HPV infections is also
real. Even though cleared by the Food and Drug Administration and recommended by
the World Federation for Ultrasound in Medicine and Biology, several disinfectants
including glutaraldehyde and ophthalaldehyde have shown a lack of efficacy for
inactivating HPV. Other methods such as ultraviolet C and concentrated hydrogen
peroxide have been shown highly effective at inactivating infectious HPV. In this
study, two chlorine dioxide systems are also shown to be highly efficacious at
inactivating HPV. An important difference in these present studies is that as opposed
to testing in suspension or using a carrier, we dried the infectious virus directly onto
endocavitary ultrasound probes and nasendoscopes, therefore, validating a more
realistic system to demonstrate disinfectant efficacy.
KEYWORDS
antiviral agents, dissemination, human papillomavirus, immune responses, papillomavirus,
pathogenesis, reinfection, virus classification
1
|
INTRODUCTION
Human papillomavirus (HPV) is a small, nonenveloped DNA virus
with over 200 types identified. These types are classified as either
highrisk for their implication in cancers in areas such as the cervix,
uterus, and head and neck, or lowrisk types, which cause benign
condylomas or warts. Types 16 and 18 are classified as highrisk and
are documented to be the most prevalent types worldwide,
1
attributable to large numbers of cancers of the cervix, uterus, anus,
and head and neck.
2,3
Sexual transmission via oral or penetrative
means is widely documented in the scientific literature and is
highlighted for its risk by healthcare institutions such as the National
Health Service and the Centers for Disease Control and Preven-
tion.
4,5
However, a source of potential transmission via fomites in the
healthcare environment from inadequate disinfection practices has
become an area of concern, debate, and discussion. Clinical areas in
which examination, diagnoses, or treatment is provided through the
use of instruments entering body cavities, cavities where HPV16 and
18 are prevalent, pose a risk to clinician and patient. Obstetrics,
gynecology, and emergency medicine departments are examples of
areas where devices including transvaginal endocavity ultrasound,
colposcopes, and speculums are used to examine the cervix and can
subsequently be contaminated with HPV.
611
Furthermore, devices
such as endoscopes used within otorhinolaryngology departments
are also at risk of HPV contamination.
The World Federation for Ultrasound in Medicine and Biology
decontamination guidelines for transvaginal ultrasound transducers
recommends disinfectants that include: 2.4% to 3.2% glutaraldehyde
------------------------------------------------------------------------------------------------------
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
(GTA), ophthalaldehyde (OPA), 7.5% hydrogen peroxide, 0.5%
bleach, ultraviolet C (UVC) radiation at 200 to 280 nm and chlorine
dioxide.
12
Our previous work in which testing was performed with
UVC radiation at 253.7 nm, 0.525% and 0.87% bleach, and 31.5%
sonicated hydrogen peroxide, has demonstrated the efficacy of these
treatments in inactivating HPV16 and 18.
1315
Where only HPV16
was tested, disinfection was not achieved with 0.55% OPA, or 2.4%
or 3.4% GTA.
1315
We, therefore, considered the next logical step for
testing would entail the assessment of chlorine dioxide, as
recommended in the guidelines noted above. These chlorine dioxide
products have been referenced in otorhinolaryngology disinfection
guidelines such as ENT UK
16
and of the Official Journal of the Italian
Society of Otorhinolaryngology.
17
Published studies show the use of
chlorine dioxide products across the globe in countries including the
UK, Australia, New Zealand, and Singapore.
1821
This report
describes the testing of two chlorine dioxide products to determine
their ability to adequately disinfect devices contaminated with HPV.
Here, we used a different approach for testing the two chlorine
dioxide solutions against HPV16 and HPV18 vs. our previous studies,
which assessed efficacy in suspension or carrierbased assays. In this
study, we contaminated actual medical devices, endocavitary ultra-
sound probes, and nasendoscopes, with the virus to simulate inuse
disinfection as closely as possible.
2
|
MATERIALS AND METHODS
2.1
|
Cell culture and virus production
HaCaT cells were maintained in Dulbecco's modified Eagle's medium
DMEM supplemented with 10% fetal bovine serum (FBS), 0.025 mg/
mL gentamicin, and 0.11 mg/mL sodium pyruvate. Primary human
keratinocytes from newborn foreskin circumcision were isolated, as
previously described.
22,23
The Human Subjects Protection Office of
the Institutional Review Board at Penn State University College of
Medicine screened our study design for exempt status according to
institutional policies and the provisions of applicable federal
regulations. They determined this study did not require formal IRB
review because no human participants are involved as defined by
federal regulations. Keratinocytes were maintained in 154 medium
supplemented with a Human Keratinocyte Growth Supplement Kit
(Cascade Biologics Inc, Portland, OR). Immortalized keratinocytes
stably maintaining HPV episomes were cultured in Emedium with
J23T3 feeder cells and grown in raft culture to produce a virus, as
previously described.
22,23
Mature virus particles were harvested
from tissues after 20 days.
2426
Rafts were harvested and the virus
was isolated by homogenization in phosphate buffer (5 mM Na
phosphate; pH 8; 2 mM MgCl
2
), as previously described.
22,23
All virus
preparations for concentration and infectivity assays were treated
with Benzonase (375 U) at 37°C for 1 hour to remove any
unencapsidated viral genomes. Samples were adjusted to 1M NaCl
and centrifuged at 4°C for 10 minutes at 10 500 rcf to remove
cellular debris.
2.2
|
Virus titers
To release the viral genomes, 10 mL of a virus preparation was
resuspended in 200 mL HIRT DNA extraction buffer (400 mM NaCl/
10 mM TrisHCl, pH 7.4/10 mM EDTA, pH 8.0), with 2 mL 20 mg/mL
Proteinase K, and 10 mL 10% sodium dodecyl sulfate for 2 hours at
37°C. The DNA was purified by phenolchloroform extraction followed
by ethanol precipitation and resuspension in 20 mL TE. Titers were
determined using a quantitative polymerase chain reaction (qPCR)based
DNA encapsidation assay utilizing a Qiagen Quantitect SYBR Green PCR
Kit.
23
Amplification of the viral genome target was performed using the
previously described E2 primers against a standard curve of 10fold
serial dilutions from 10
8
to 10
4
copies per mL.
23
For infection assays,
HaCaT cells were seeded in 24well plates with 50 000 cells per well
2 days before infection. Compounds were mixed with virus and media in
a total volume of 500 µL before addition to cells. An multiplicity of
infection (MOI) of 10 particles per cell was used unless otherwise noted.
The virus was incubated with the cells for 48 hours at 37°C and
messenger RNA was harvested using a Qiagen RNAeasy Kit.
2.3
|
Instrument preparation
Instruments tested were (a) nasendoscopes and (b) endocavity
ultrasound probes. An organic load (soil) of 5% FBS was added to
the virus suspension and spread along the length of the insertion
tube of each device, representing the part of the instrument exposed
to the patient. The inoculated instruments were allowed to dry in a
laminar flow cabinet for 30 minutes or until dry.
2.4
|
Disinfectants
The two chlorine dioxide disinfection procedures used were from Tristel
Solutions Limited: (a) the Tristel Trio Wipes System and (b) Tristel Duo.
The ability of each procedure to inactivate authentic HPV16 and 18 was
evaluated separately. As a positive disinfection control, sodium hypo-
chlorite was used at the manufacturer's recommended concentration of
0.87% (8700 parts per million) (Pure Bright Germicidal Ultra Bleach, KIK
International). The use of this control was based on its previously
demonstrated efficacy against HPV16 and 18, in both suspension and
carrier tests.
14,15
To control for virus recovery after drying onto the
probe, some probes were not treated with disinfectant and the virus was
removed and tested for infectivity, as described below. All disinfectant
products were used according to the manufacturer's instructions for use.
2.5
|
Disinfection procedure
The endocavity ultrasound probe and nasendoscope were disinfected
using a threestep Tristel Trio Wipes System. This included a preclean
wipe to clean the instruments, a sporicidal wipe to disinfect the
instrument with a contact time of 30 seconds, and a rinse wipe to
2
|
MEYERS ET AL.
remove any chemical residue. This procedure replicates the standard
decontamination guidelines for semicritical medical devices, which
includes a cleaning step, a disinfection step, and a rinsing step.
The second set of endocavity ultrasound probes (Siemens)
was disinfected by first using a preclean wipe to replicate the
removal of ultrasound gel from a sheath that would be present on a
device after a clinical procedure. The device was then disinfected
with two aliquots of Tristel Duo applied via a low linting Duo Wipe,
utilizing a 30 second contact time for efficacy.
Nasendoscopes (Karl Storz Medical Supplies) were also used for
testing and were similarly treated with Tristel Duo and the Duo Wipe,
except no initial cleaning procedure, was performed. The omission of the
cleaning step was to replicate a worstcase scenario wherein the cleaning
step may be missed, or if soiling remained on the device postcleaning.
After the procedures, a base neutralizer (7% glycine) was used
to rinse and scrape 2X the chlorine dioxide treated instruments,
after which they were washed 2X with phosphatebuffered saline
(PBS) to dilute any residues of chlorine dioxide left and halt
further action. All samples were filtered and washed with HaCat
cell media 3X and assayed for infectivity as previously de-
scribed.
15
All disinfection efficacy tests were conducted in
triplicate with separate batches of the virus.
2.6
|
HPV infectivity assay
Infection was analyzed using a previously described RTqPCR
based infectivity assay for E1^E4 transcript levels.
23
The E1^E4
spliced transcript was amplified using primers specific for the
spliced transcript. HPV16 and 18 infectivity assays were
performed using HaCat cells, as previously described.
22,23
Complete viral inactivation was considered achieved when post
disinfection infectivity assays showed equivalent or higher
C
t
values than uninfected controls.
3
|
RESULTS
The chlorine dioxide solutions were able to produce a >99.99%
reduction in infectivity of HPV16 and 18 with soil (5% BSA) included
in the assays (Figure 1). The reduction is similar to that seen with
0.87% sodium hypochlorite. The differences seen in the log
10
reduction values between the tests with the same virus type and
between virus types reflect different starting titers.
The efficacy of chlorine dioxide on HPV16 was similar to that of
sodium hypochlorite in our previous study, the difference is that the
previous testing was performed in a suspensionbased assay, mixing
the virus with the disinfectant in solution and not by applying the
virus directly onto the devices, as we have done in this present study.
But it did allow us to determine the differences in efficacy between
different chemical groups: alcohols (ethanol, isopropanol), aldehydes
(GTA, OPA), phenol and oxidizing agents (PAAsilver, sodium
hypochlorite, chlorine dioxide).
14
4
|
DISCUSSION
In this study, we report the first results of two procedures simulating
inuse disinfection of native HPV16and HPV18contaminated
devices. These findings support our previous work, which demon-
strates that oxidizing chemistries, including hydrogen peroxide,
peracetic acid blended with silver, sodium hypochlorite,
13,15,27
and
now chlorine dioxide, are effective at inactivating both HPV16 and
HPV18.
These results show that a manual procedure can be used to
disinfect HPVcontaminated devices that may not withstand methods
that utilize submersion, heat, or radiation. The endocavity ultrasound
probes (Siemens) and nasendoscopes (Karl Storz Medical Supplies)
used for our study are representative of these devices with each
device having their unique curves, ridges, and cavities that can affect
the appropriate disinfection.
0
1
2
3
4
5
6
0
1
2
3
4
5
6
7
Log10 Reducon of HPV16 Infecon
Log10 Reducon of HPV18 Infecon
(A)
(B)
FIGURE 1 Susceptibility of HPV16 and HPV18 virions to chlorine
dioxide disinfectants. A total of 1 × 10
7
HPV16 (A) or HPV18 (B) particles
were mixed with organic soil (5% FBS) and dried onto the nasendoscope
(Nas) or transvaginal (TV) ultrasound probes. Two different chlorine
dioxide disinfection procedures were tested; Tristel Duo (Duo) and
Tristel Trio Wipes (Trio), As a control for infectious virus recovery,
HPV16 and HPV18 were mixed with soil and dried onto probes, but no
disinfection procedure was included. Hypochlorite was included as a
positive control for disinfection efficacy. Graphs show log
10
reduction of
infectivity for each condition tested. HaCat cells were used for the
infectivity assays. The dotted line marks the FDA required 4 log
10
reductions. FDA, Food and Drug Administration
MEYERS ET AL.
|
3
Furthermore and more importantly, it provides a solution to
those devices that are also mobile/transportable, such as those used
within the community setting by healthcare practitioners. In these
scenarios, a transportable, simple method that achieves disinfection
efficacy in short contact time, is sorely needed.
Medical devices for examination/diagnoses that can be used in a
high patient throughput manner and be transported easily are
becoming more prevalent in the healthcare industry, especially in
developing countries. A good example of this is mobile colposcopy.
These devices are used to examine the cervix and determine any
abnormal cells or precancerous lesions that may be present. These
same countries are less likely to be able to afford an automated
disinfection system, and an easily transported, nonmachinebased
system for disinfection would be of great benefit.
HPV is a nonenveloped virus, which has demonstrated resistance
to many disinfectants, including those which are Food and Drug
Administration cleared for highlevel disinfection (GTA, OPA).
1315
Current guidelines require highlevel disinfection of ultrasound
probes used in semicritical applications including procedures that
may involve contact with mucous membranes or broken skin.
28
By
definition, highlevel disinfection refers to the complete elimination
of all viruses and microorganisms, with the exception of bacterial
endospores, some of which are permitted to remain.
28
Some devices make close contact with the patient in areas in
which HPV is prevalent, and studies have demonstrated that
colposcopes are contaminated with HPV DNA, as are the glove
boxes used by medical practitioners.
8
Although DNA detection does
not necessarily indicate the presence of viable and infective
microorganisms, the work of M'Zali et al
9
showed that HPV virions
remain present on ultrasound devices used in women's healthcare,
following standard disinfection protocols. This indicates that stan-
dard protocols are inadequate to properly disinfect these devices,
putting both patient and clinician at risk for HPV transmission.
In addition to those devices used in women's healthcare, devices
that enter the mucosal cavity of the head and neck are also at risk for
contamination with HPV. In the case of emergency (eg, ambulatory)
and point of use care, instruments such as those used to intubate
patients with breathing difficulties, are exposed to mucosal secre-
tions. To aid in the quick turnaround of device usage, manual
disinfection procedures could be pivotal. It may also save in overall
healthcare costs, as rapid disinfection methods would reduce
device reprocessing downtime and also reduce the number of
required devices.
A steady increase in carcinomas of the head and neck has been
reported in many countries including New Zealand,
29
Sweden,
30,31
Denmark,
32
and the United States.
33
Presence of HPV DNA within
tumor samples has been demonstrated through PCR amplification of
specific gene sections, indicative of active HPV infection. Furthermore,
data demonstrate the percentage of male patients positive for HPV in
the carcinomas of the head and neck is higher than that of females. It is
postulated that the higher prevalence in men may be due to the higher
viral load of HPV within the vagina and cervix than on the penis.
34
Research from Hernandez et al
35
supports these findings, revealing
transmission of HPV is higher from the cervix to the penis than from
the penis to the vagina. Thus, it is possible that transmission of HPV
during oral sex of a man with a woman may be more likely to occur
than the oral sex of a woman with a man, providing a potential
explanation for the differing percentages seen. This adds another level
to the importance of controlling the potential of high contamination
rates on devices used in the head and neck area.
ORCID
Craig Meyers http://orcid.org/0000-0001-8773-3976
Janice Milici http://orcid.org/0000-0001-9185-1457
Richard Robison http://orcid.org/0000-0002-4324-5169
REFERENCES
1. Forman D, de Martel C, Lacey CJ, et al. Global burden of human
papillomavirus and related diseases. Vaccine. 2012;30(suppl 5):F12
F23. https://doi.org/10.1016/j.vaccine.2012.07.055
2. Serrano B, de Sanjosé S, Tous S, et al. Human papillomavirus
genotype attribution for HPVs 6, 11, 16, 18, 31, 33, 45, 52 and 58 in
female anogenital lesions. Eur J Cancer. 2015;51(13):17321741.
https://doi.org/10.1016/j.ejca.2015.06.001
3. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden
of cancer attributable to HPV by site, country and HPV type. Int J
Cancer. 2017;141(4):664670. https://doi.org/10.1002/ijc.30716
4. National Health Service. A guide to throat cancer caused by oral HPV
(human papilloma virus in the mouth/throat) infection. [Internet].
2018. https://www.hey.nhs.uk/patientleaflet/gudiethroatcancer
causedoralhpvhumanpapillomavirusmouththroatinfection
5. Centers for Disease Control and Prevention. Human papillomavirus.
[Internet]. 2019. https://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html
6. Strauss S, Sastry P, Sonnex C, Edwards S, Gray J. Contamination of
environmental surfaces by genital human papillomaviruses. Sex
Transm Infect. 2002;78(2):135138.
7. Ferenczy A, Bergeron C, Richart RM. Carbon dioxide laser energy
disperses human papillomavirus deoxyribonucleic acid onto treat-
ment fields. Am J Obstet Gynecol. 1990;163(4 Pt 1):12711274.
8. Gallay C, Miranda E, Schaefer S, et al. Human papillomavirus (HPV)
contamination of gynaecological equipment. Sex Transm Infect. 2016;
92(1):1923. https://doi.org/10.1136/sextrans2014051977
9. M'Zali F, Bounizra C, Leroy S, Mekki Y, QuentinNoury C, Kann M.
Persistence of microbial contamination on transvaginal ultrasound
probes despite lowlevel disinfection procedure. PLoS One. 2014;9(4):
e93368. https://doi.org/10.1371/journal.pone.0093368
10. Ma ST, Yeung AC, Chan PK, Graham CA. Transvaginal ultrasound
probe contamination by the human papillomavirus in the emergency
department. Emerg Med J. 2013;30(6):472475. https://doi.org/10.
1136/emermed2012201407
11. Casalegno J, Le Bail Carval K, Eibach D, et al. High risk HPV
contamination of endocavity vaginal ultrasound probes: an under-
estimated route of nosocomial infection? PLoS One. 2012;7(10):
e48137. https://doi.org/10.1371/journal.pone.0048137
12. Abramowicz JS, Evans DH, Fowlkes JB, Maršal K, terHaar G.
Guidelines for cleaning transvaginal ultrasound transducers between
patients. Ultrasound Med Biol. 2017;43(5):10761079. https://doi.org/
10.1016/j.ultrasmedbio.2017.01.002
13. Meyers C, Milici J, Robison R. UVC radiation as an effective
disinfectant method to inactivate human papillomaviruses. PLoS
One. 2017;12(10):e0187377. https://doi.org/10.1371/journal.pone.
0187377
4
|
MEYERS ET AL.
14. Ryndock E, Robison R, Meyers C. Susceptibility of HPV16 and 18 to
high level disinfectants indicated for semicritical ultrasound probes.
J Med Virol. 2016;88(6):10761080. https://doi.org/10.1002/jmv.
24421
15. Meyers J, Ryndock E, Conway MJ, Meyers C, Robison R. Suscept-
ibility of highrisk human papillomavirus type 16 to clinical
disinfectants. J Antimicrob Chemother. 2014;69(6):15461550.
https://doi.org/10.1093/jac/dku006
16. ENT UK. Otorhinolaryngology disinfection gudielines. [Internet].
2017. https://www.entuk.org/
17. Cavaliere M, Iemma M. Guidelines for reprocessing nonlumened
heatsensitive ear/nose/throat endoscopes. Laryngoscope. 2012;
122(8):17081718. https://doi.org/10.1002/lary.23389
18. Lomas J, Chandran D, Whitfield BCS. Surgical management of plunging
ranulas: a 10year case series in South East Queensland. ANZ J Surg.
2018;88(10):10431046. https://doi.org/10.1111/ans.14356
19. Hitchcock B, Moynan S, Frampton C, Reuther R, Gilling P, Rowe F. A
randomised, singleblind comparison of highlevel disinfectants for
flexible nasendoscopes. J Laryngol Otol. 2016;130(11):983989.
https://doi.org/10.1017/S0022215116008860
20. Gan YJ, Mathews A, Chuqin P, Khoo I, Loke D. Flexible nasoendo-
scopy decontamination: a comparison between Rapicide and Tristel
wipes, a prospective cohort study. Int J Otorhinolaryngol Head Neck
Surg. 2018;4(1):1823. https://doi.org/10.18203/issn.24545929.
ijohns20175607
21. Tzanidakis D, Choudhury N, Bhat S, Weerasinghe A, Marais J.
Evaluation of disinfection of flexible nasendoscopes using Tristel
wipes: a prospective single blind study. Ann R Coll Surg Engl. 2012;94:
185188. https://doi.org/10.1308/003588412X3171221589937
22. Conway MJ, Cruz L, Alam S, Christensen ND, Meyers C. Cross
neutralization potential of native human papillomavirus Nterminal
L2 epitopes. PLoS One. 2011;6(2):e16405. https://doi.org/10.1371/
journal.pone.0016405
23. Biryukov J, Cruz L, Ryndock EJ, Meyers C. Native human papillomavirus
production, quantification, and infectivity analysis. Methods Mol Biol. 2015;
1249:317331. https://doi.org/10.1007/9781493920136_24
24. Conway MJ, Alam S, Ryndock EJ, et al. Tissuespanning redox
gradientdependent assembly of native human papillomavirus type
16 virions. J Virol. 2009;83(20):1051510526. https://doi.org/10.
1128/JVI.0073109
25. Conway MJ, Cruz L, Alam S, Christensen ND, Meyers C.
Differentiationdependent interpentameric disulfide bond stabilizes
native human papillomavirus type 16. PLoS One. 2011;6(7):e22427.
https://doi.org/10.1371/journal.pone.0022427
26. Israr M, Biryukov J, Ryndock EJ, Alam S, Meyers C. Comparison of
human papillomavirus type 16 replication in tonsil and foreskin
epithelia. Virology. 2016;499:8290. https://doi.org/10.1016/j.virol.
2016.09.004
27. Ryndock EJ, Conway MJ, Alam S, et al. Roles for human papilloma-
virus type 16 l1 cysteine residues 161, 229, and 379 in genome
encapsidation and capsid stability. PLoS One. 2014;9(6):e99488.
https://doi.org/10.1371/journal.pone.0099488
28. Rutala WA, Weber DJ Healthcare Infection Control Practices
Advisory Committee (HICPAC). Guideline for Disinfection and Steriliza-
tion in Healthcare Facilities. Atlanta, GA: Centers for Disease Control;
2008.
29. LucasRoxburgh R, Benschop J, Lockett B, van den Heever U,
Williams R, Howe L. The prevalence of human papillomavirus in
oropharyngeal cancer in a New Zealand population. PLoS One. 2017;
12(10):e0186424. https://doi.org/10.1371/journal.pone.0186424
30. Hammarstedt L, Lindquist D, Dahlstrand H, et al. Human papilloma-
virus as a risk factor for the increase in incidence of tonsillar cancer.
Int J Cancer. 2006;119(11):26202623. https://doi.org/10.1002/ijc.
22177
31. Nasman A, Attner P, Hammarstedt L, et al. Incidence of human
papillomavirus (HPV) positive tonsillar carcinoma in Stockholm,
Sweden: an epidemic of viralinduced carcinoma? Int J Cancer.
2009;125(2):362366. https://doi.org/10.1002/ijc.24339
32. Carlander ALF, Grønhøj Larsen C, Jensen DH, et al. Continuing rise in
oropharyngeal cancer in a high HPV prevalence area: A Danish
populationbased study from 2011 to 2014. Eur J Cancer. 2017;70:75
82. https://doi.org/10.1016/j.ejca.2016.10.015
33. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus
and rising oropharyngeal cancer incidence in the United States. J Clin
Oncol. 2011;29(32):42944301. https://doi.org/10.1200/JCO.2011.
36.4596
34. D'Souza G, Dempsey A. The role of HPV in head and neck cancer and
review of the HPV vaccine. Prev Med. 2011;53(suppl 1):S5S11.
https://doi.org/10.1016/j.ypmed.2011.08.001
35. Hernandez BY, Wilkens LR, Zhu X, et al. Transmission of human
papillomavirus in heterosexual couples. Emerg Infect Dis. 2008;14(6):
888894. https://doi.org/10.3201/eid1406.070616
How to cite this article: Meyers C, Milici J, Robison R. The
ability of two chlorine dioxide chemistries to inactivate human
papillomaviruscontaminated endocavitary ultrasound probes
and nasendoscopes. J Med Virol. 2020;15.
https://doi.org/10.1002/jmv.25666
MEYERS ET AL.
|
5
... Disposable single or multistep wipes utilize chemicals such as chlorine dioxide. They are reported to require 2-3 min per disinfection and are effective at eradicating pathogens, including HPV [16][17][18][19][20][21] . Although chlorine dioxide is toxic, single and multistep wipes are easier to dispose of and are safer than chemical baths [16][17][18][19]22 . ...
Article
Full-text available
Objectives: To compare the efficiency, ease of use and user satisfaction of two methods of transvaginal ultrasound probe high-level disinfection: ultraviolet-C radiation (UV-C) and a chlorine dioxide multistep wipe system. Methods: This was a prospective survey study. UV-C units were introduced into a busy early pregnancy assessment service and compared with a multiwipe system for disinfection. Before seeing each patient, healthcare professionals (HCPs) measured with a stopwatch the time taken to complete a cycle of disinfection using either UV-C or chlorine dioxide multistep wipes and responded to a quick-response (QR) code-linked survey. Additional essential tasks that could be completed before seeing the next patient during probe disinfection were also documented. Using another QR code-linked survey, data on ease of use, satisfaction with the system used and preferred system were collected. The ease of use and satisfaction with the system were rated on a 0 to 10 Likert scale (0 poor, 10 excellent). A free-text section for comments was then completed. Results: Disinfection using UV-C (n = 331) was 60% faster than the chlorine dioxide multiwipe system (n = 332) (101 vs 250 s; P < 0.0001). A greater number of tasks were completed during probe disinfection when using UV-C, saving a further 74 s per patient (P < 0.0001). The HCPs using UV-C (n = 71) reported greater ease of use (median Likert score, 10 vs 3; P < 0.0001) and satisfaction (median Likert score, 10 vs 2; P < 0.0001) compared with those using the multiwipe system (n = 43). HCPs reported that the chlorine dioxide system was time-consuming and environmentally unfriendly, while the UV-C system was efficient and easy to use. Overall, 98% of the HCPs preferred using the UV-C system. Conclusions: UV-C technology is more time-efficient and allows more essential tasks to be completed during disinfection. For a 4-h ultrasound list of 15 patients, the use of UV-C would save 55 min 45 s. HCPs found UV-C preferable and easier to use. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
... A very recent review on dermatologic reactions to various types of disinfectants used to reduce the risk of coronavirus infection indicated that ClO 2 is safe, even with prolonged skin contact [8] . ClO 2 solution is also closely examined for its potential use to inactivate viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [9] and human papillomavirus (HPV) [10] . Interestingly, ClO 2 solution was also used to sterilize recycled KN95s or surgical face masks during critical shortage of such supplies [2] . ...
Article
Full-text available
Chlorine dioxide plays a significant role in the industrial settings as disinfectants due to its broad antimicrobial property. Despite commonly use as germicide, chlorine dioxide demonstrates a good safety profile, rendering its suitability for use at water treatment and food preparation zones. Protein denaturation including envelope proteins is the major mechanism of chlorine dioxide to inactivate microorganisms even at low concentrations. Adverse reactions are not widely reported due to the typical use at a low concentration. The effectiveness of chlorine dioxide against various microorganisms, in both liquid and gaseous forms, over a wide range of pH and at an extremely low concentration has confirmed chlorine dioxide as a vital and versatile disinfectant.
Article
Human papillomavirus (HPV) is thought to be sexually transmitted; however, there have been a few studies investigating a possible iatrogenic source of infection. Therefore, it is important to assess cleaning methods of reusable medical devices. This study assessed whether cleaning methods of flexible endoscopes in an otolaryngology clinic are effective against HPV. There were 24 patients with a history of head and neck cancer in the study; however, two outliers were excluded. Nine patients were confirmed to have HPV‐associated cancer. PCR was used to measure and quantify the viral genomes of samples collected before and after cleaning. After cleaning, few HPV+ samples had endoscopes with less DNA than before cleaning. Additionally, for several patients with non‐HPV‐associated head and neck cancer, PCR showed more DNA after cleaning than before cleaning, suggesting residual HPV DNA within the cleaning solution. There was no significant difference (p > 0.05) between pre‐and‐post cleaning in both cohorts. Current cleaning methods of reusable endoscopes may not be effective in completely removing viral DNA. This article is protected by copyright. All rights reserved.
Article
Medical instruments that are not autoclavable but may become contaminated with high‐risk human papillomaviruses (HPV) during use must be thoroughly disinfected to avoid the possibility of iatrogenic transmission of infection. There is an expectation that prolonged soaking of instruments in US‐FDA‐cleared chemical disinfectant solutions will result in high‐level decontamination, but HPV16 and HPV18 are known to be resistant to commonly used formulations. However, they are susceptible to a variety of oxidative agents, including those based on chlorine. Here, we tested the efficacy of homogeneous hypochlorous acid (HOCl) solutions against mature infectious virions of HPV16 and HPV18 dried onto butadiene styrene coupons and ultrasonic probes. Both viruses were inactivated to >4 log reduction value (LRV) after 15s on coupons and 5 mins on ultrasonic probes. Morphologic changes became evident within those contact times by transmission electron microscopy when HPV16 virus‐like particles (VLPs) were exposed to HOCl under identical conditions. Mass spectrometry analysis of trypsin‐digested products of L1 capsid proteins exposed to HOCl showed that mostly conserved residues were modified by oxidation, and that these changes rapidly lead to instability of the protein demonstrable on SDS‐PAGE. Modifications to these residues may contribute to rapid virus inactivation. Use of homogeneous HOCl solutions for HPV decontamination provides a highly effective means of assuring the safety of non‐autoclavable medical instruments. This article is protected by copyright. All rights reserved.
Article
Full-text available
Endocavitary ultrasound probes are part of a commonly used procedure in the clinical arena. The cavities examined, vaginal canal and cervix, anal canal, and oral cavity are all areas commonly infected with the human papillomavirus (HPV), thus making them susceptible to contamination by HPV. It has been demonstrated that these probes can remain contaminated with high-risk HPV even when approved disinfection protocols have been performed. we have previously shown that HPV is resistant to some high-level disinfectant (HLD). In our present study we analyzed efficacy of using high-level ultra-violet C (UVC) radiation against HPV16 and HPV18 using a hard-surface carrier test. Stocks of infectious authentic HPV16 and HPV18 virions were dried onto carriers with a 5% (v/v) protein soil or 4ppm hard water. Efficacy testing were performed with the automated device, Antigermix S1 device (UVC radiation at 253.7nm) and 0.55% OPA in quadruplicate with matched input, neutralization, and cytotoxicity controls. Hypochlorite was included as a positive control for viral deactivation. Infectivity was determined by the abundance (qRT-PCR) of the spliced E1^E4 transcript in infected recipient cells. The automated Antigermix S1 device showed excellent efficacy against HPV16 and HPV18 whereas OPA showed minimal efficacy. While HPV is highly resistant to OPA, high-level UVC radiation offers an effective disinfection practice for ultrasound probes. Our results suggest that healthcare facilities using endocavitary ultrasound probes need to strongly consider disinfection methods that are effective against HPV.
Article
Full-text available
Background The incidence of oropharyngeal cancer (OPC) in New Zealand (NZ) has more than doubled over the last 14 years with 126 cases in 2010. Overseas studies have shown that human papillomavirus (HPV) plays a significant role in the development of these cancers. However, the role of HPV in OPC and the burden on the NZ health system is unclear. Aim The aim of the study was to determine the prevalence and the genotypes of HPV associated with OPC in New Zealand. Methods In this study, 621 OPC were identified from cancer registry data from 1996–98, 2003–05, and 2010–12. Biopsies of 267 cases were then retrieved from laboratories throughout New Zealand. p16 immunohistochemistry and a human beta globin PCR were performed on all specimens. HPV genotyping was performed on all beta globin positive specimens using real-time PCR with melt analysis. Results Using a p16/PCR algorithm, 77.9% (95% CI: 71.1–83.5%) of cases were attributable to HPV. Of these, 98.5% were HPV 16 positive. There was also one case each of HPV 33 and 35. The percentage of HPV positive cases increased from 61.9% (95% CI: 40.9%– 79.2%) in 1996–98 to 87.5% (95% CI: 79.8%– 92.5%) in 2010–12. Results from the multivariable model, adjusted for sex and ethnicity found statistically significant associations between HPV positivity and timeframe (OR: 5.65, 95% CI: 2.60–12.30, 2010–12 vs 1996–98), and between HPV positivity and patient age (OR: 0.55, 95% CI: 0.33–0.99, ≥61 years vs ≤60 years). Conclusions This data is consistent with data from other developed countries showing an increase in cases of HPV positive OPC in New Zealand, and the majority of cases being attributable to HPV 16. These results support the recent inclusion of males into the nationally funded immunization schedule for Gardasil® 9.
Article
Full-text available
HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancer and oropharyngeal cancer. Understanding the HPV-attributable cancer burden can boost programs of HPV vaccination and HPV-based cervical screening. Attributable fractions (AF) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age-standardized incidence rates of HPV-attributable cancers by country from GLOBOCAN 2012 data are shown separately for the cervix, other anogenital tract, and head and neck cancers. The relative contribution of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 was also estimated. 4.5% of all cancers worldwide (630,000 new cancer cases per year) are attributable to HPV: 8.6% in women and 0.8% in men. AF in women ranges from <3% in Australia/New Zealand and the USA to >20% in India and sub-Saharan Africa. Cervix accounts for 83% of HPV-attributable cancer, two-thirds of which occur in less developed countries. Other HPV-attributable anogenital cancer includes 8,500 vulva; 12,000 vagina; 35,000 anus (half occurring in men); and 13,000 penis. In the head and neck, HPV-attributable cancers represent 38,000 cases of which 21,000 are oropharyngeal cancers occurring in more developed countries. The relative contributions of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 are 73% and 90%, respectively. Universal access to vaccination is the key to avoiding most cases of HPV-attributable cancer. The preponderant burden of HPV16/18 and the possibility of cross-protection emphasize the importance of the introduction of cheaper vaccines in less developed countries. This article is protected by copyright. All rights reserved.
Article
Full-text available
Human papillomavirus (HPV) is well recognized as a causative agent for anogenital and oropharyngeal cancers, however, the biology of HPV infection at different mucosal locations, specifically the oral cavity, is not well understood. Importantly, it has yet to be determined if oral tissues are permissive for HPV infection and replication. We investigated for the first time the titers, infectivity, and maturation of HPV16 in oral epithelial versus genital epithelial tissue. We show that infectious HPV16 virions can be produced in oral tissue. This demonstrates, for the first time, that infectious virus could be spread via the oral cavity. HPV16 derived from oral tissue utilize a tissue-spanning redox gradient that facilitates the maturation of virions over time. Maturation is manifested by virion stability and increased susceptibility to neutralization with anti-HPV16 L1 antibodies. However, susceptibility to neutralization by anti-HPV16 L2 specific antibodies decreases during the maturation of HPV16 virions in oral tissue.
Article
Full-text available
Background: Ultrasound probes used in endocavitary procedures have been shown to be contaminated with high-risk HPV after routine use and HPV is also known to be resistant to some high level disinfectants (HLDs). This study compared efficacy of two leading ultrasound probe HLD methods; liquid ortho-phthalaldehyde (Cidex® OPA) and an automated device using sonicated hydrogen peroxide (trophon® EPR) against HPV16 and HPV18 in a hard-surface carrier test. Methods: Native HPV16 and HPV18 virions were generated in organotypic epithelial raft cultures. Viral lysates were dried onto carriers with a 5% (v/v) protein soil. Efficacy tests were performed against the automated device at 35% and 31.5% H2 O2 and 0.55% OPA in quadruplicate with matched input, neutralization and cytotoxicity controls. Hypochlorite was included as a positive control. Infectivity was determined by the abundance (qRT-PCR) of the spliced E1^E4 transcript in infected recipient cells. Results: The automated HLD device showed excellent efficacy against HPV16 and HPV18 (>5 log10 reductions in infectivity) whereas OPA showed minimal efficacy (<0.6 log10 reductions). Conclusions: While HPV is highly resistant to OPA, sonicated hydrogen peroxide offers an effective disinfection solution for ultrasound probes. Disinfection methods that are effective against HPV should be adopted where possible. This article is protected by copyright. All rights reserved.
Article
p class="abstract"> Background: The current disinfection of nasoendoscopes in our clinic setting is a 3-step process involving Rapicide, a peracetic acid based disinfectant. Our study aimed to validate the efficacy of Tristel wipes, a chlorine dioxide based disinfectant, as a comparable alternative. Methods: We recruited a hundred volunteers undergoing routine flexible nasoendoscopic examinations in a general ENT. We used two separate endoscopes for each examination, following which a microbiological swab was sent from the tip of each nasoendoscope. The two nasoendoscopes were then subjected to a similar 3-step decontamination process except for the second step, where they were disinfected either tristel wipes or rapicide disinfectant. After decontamination, we took a second swab from the tip of each nasoendoscope. Results: Out of 200 swabs from the tip of the nasoendoscopes prior to decontamination, there were 82 positive cultures for the Rapicide cohort and 76 positive cultures for the Tristel wipes cohort. Regarding the post decontamination results, there were four positive swab cultures for those disinfected with Tristel wipes and one positive swab culture for the Rapicide cohort. These were analyzed by the Z score and there was no statistical difference between either the pre-decontamination swabs or the post decontaminations swabs with the p-values at p=0.298 and p=0.174 respectively. The efficacy of decontamination for the Rapicide solution was 98.8% compared to 94.7% for the Tristel wipes with p=0.147. Conclusions: This study validates the efficacy of Tristel wipes as a comparable alternative to peracetic acid based disinfectants for disinfection of flexible nasoendoscopes. </p
Article
Background: Plunging ranulas are rare mucous extravasation pseudocysts that arise in the floor of the mouth and pass into the submandibular space of the neck. The aim of this study was to investigate the diagnosis, surgical management and outcomes of patients with a plunging ranula at our institution in South East Queensland over a 10-year period. Methods: A retrospective analysis of adult patients diagnosed with and treated for plunging ranula between 2006 and 2016 at Logan Hospital was conducted. Patient demographics, preoperative investigations, surgical management and post-operative outcomes were collected from medical records. Results: A total of 18 adult patients were treated for plunging ranula. Of the 18 cases, 17 were treated via transoral excision of the sublingual gland. The mean age at presentation was 28.8 years with a 3:1 female to male predominance. Fifty-six percent of patients were of Polynesian descent. The success rate was 94% with only one patient experiencing recurrence and requiring re-excision of remnant sublingual gland tissue. Three patients (17%) developed complications related to post-operative bleeding. There was a slight predominance for right-sided disease (56%) compared with left and one case of bilateral plunging ranulas in this series. Conclusion: This study demonstrates that excision of the sublingual gland is an effective and safe treatment for plunging ranula. The majority of plunging ranulas occur in patients aged <30 years with a higher incidence in patients of Polynesian heritage, which is consistent with previous studies suggesting a possible underlying genetic predisposition for this condition.
Article
The purpose of this article is to provide guidance regarding the cleaning and disinfection of transvaginal ultrasound probes. These recommendations are also applicable to transrectal probes.
Article
Background: Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020. Patients and methods: Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing. Results: Sixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. Conclusion: An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.
Article
Objectives: To compare the microbiological efficacy, turnaround time, cost, convenience, and patient and user tolerance of Tristel Trio Wipes, PeraSafe solution and Cidex OPA solution for the high-level disinfection of flexible nasendoscopes. Methods: Flexible nasendoscopes were used in routine clinical encounters. They were then disinfected with one of the three disinfectant methods. Surveillance cultures were taken before and after each disinfection process. Data relating to each of the study parameters were recorded. Results: Positive bacterial cultures were discovered on nasendoscopes disinfected with PeraSafe and Cidex OPA. Tristel Trio Wipes have no capital outlay cost, the lowest running cost, the greatest convenience and the fastest turnaround time. PeraSafe had a faster turnaround time than Cidex OPA, and lower running costs. Conclusion: Tristel Trio Wipes are equal to PeraSafe and Cidex OPA in terms of microbiological efficacy. Turnaround time and cost are dramatically reduced when using Tristel Trio Wipes compared to the other disinfectant methods.