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Adjuvant treatments for recurrent respiratory papillomatosis: a descriptive review and proposed management guideline in adults

Published online by Cambridge University Press:  21 October 2024

Edward Balai Open the ORCID record for Edward Balai [Opens in a new window] ,
Emilie AC Dronkers Open the ORCID record for Emilie AC Dronkers [Opens in a new window] ,
Chadwan A Yaghchi ,
Dorothy Gujral ,
Guri Sandhu  and
Aphrodite Iacovidou
Edward Balai*
Affiliation:
Department of Otolaryngology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
Emilie AC Dronkers
Affiliation:
National Centre for Airway Reconstruction, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
Chadwan A Yaghchi
Affiliation:
National Centre for Airway Reconstruction, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
Dorothy Gujral
Affiliation:
Department of Surgery and Cancer, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
Guri Sandhu
Affiliation:
National Centre for Airway Reconstruction, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
Aphrodite Iacovidou
Affiliation:
National Centre for Airway Reconstruction, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
*
Corresponding author: Edward Balai; Email: [email protected]
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Abstract

Objective

Recurrent respiratory papillomatosis is a rare disease characterised by growth of papilloma within the respiratory tract. The disease course is variable but can require frequent surgical interventions alongside adjuvant medical treatments. There is no definitive curative treatment or gold-standard guidelines for management. We aimed to evaluate current and potential future adjuvant treatments and propose a management guideline for adult patients.

Methods

Relevant articles were identified through searching databases, reference lists and grey literature.

Results

Systemic bevacizumab appears to be the most effective adjuvant treatment currently available. However, intralesional cidofovir also achieves a high complete-response rate in adults and the Gardasil vaccine demonstrates preventative and therapeutic value. The INO-3107 DNA vaccine is a promising potential future adjuvant treatment.

Conclusions

This review provides a detailed examination of current and potential future adjuvant treatments. Based on the literature, we have developed a management guideline for adult patients with recurrent respiratory papillomatosis.

Keywords

larynxendoscopylaserdysphoniatracheapapillomatosis
Type
Main Article
Information
The Journal of Laryngology & Otology , Volume 138 , Issue 12 , December 2024 , pp. 1133 - 1143
Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED

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Footnotes

Edward Balai takes responsibility for the integrity of the content of the paper

References

San Giorgi, MRM, van den Heuvel, ER, Tjon, REA, Brunings, JW, Chirila, M, Friedrich, G et al. Age of onset of recurrent respiratory papillomatosis: a distribution analysis. Clin Otolaryngol 2016;41:448–53CrossRefGoogle ScholarPubMed
Derkay, CS, Wiatrak, B. Recurrent respiratory papillomatosis: a review. Laryngoscope 2008;118:1236-47CrossRefGoogle ScholarPubMed
Derkay, CS, Malis, DJ, Zalzal, G, Wiatrak, BJ, Kashima, HK, Coltrera, MD. A staging system for assessing severity of disease and response to therapy in recurrent respiratory papillomatosis. Laryngoscope 1998;108:935–7CrossRefGoogle ScholarPubMed
Kupfer, RA, Tatar, EÇ, Barry, JO, Allen, CT, Merati, AL. Anatomic Derkay score is associated with voice handicap in laryngeal papillomatosis in adults. Otolaryngol Head Neck Surg 2016;154:689–92CrossRefGoogle ScholarPubMed
Fortes, HR, von Ranke, FM, Escuissato, DL, Araujo Neto, CA, Zanetti, G, Hochhegger, B et al. Recurrent respiratory papillomatosis: a state-of-the-art review. Respir Med 2017;126:116–21CrossRefGoogle ScholarPubMed
Oh, ST, Longworth, MS, Laimins, LA. Roles of the E6 and E7 proteins in the life cycle of low-risk human papillomavirus type 11. J Virol 2004;78:2620–6CrossRefGoogle ScholarPubMed
Syrjänen, K, Hakama, M, Saarikoski, S, Väyrynen, M, Yliskoski, M, Syrjänen, S et al. Prevalence, incidence, and estimated life-time risk of cervical human papillomavirus infections in a nonselected Finnish female population. Sex Transm Dis 1990;17:15–19CrossRefGoogle Scholar
Sivasankar, M, Erickson, E, Rosenblatt, M, Branski, RC. Hypertonic challenge to porcine vocal folds: effects on epithelial barrier function. Otolaryngol Head Neck Surg 2009;142:79–84CrossRefGoogle ScholarPubMed
Bonagura, VR, Hatam, LJ, Rosenthal, DW, De Voti, JA, Lam, F, Steinberg, BM et al. Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus-6 and -11. APMIS 2010;118:455–70CrossRefGoogle ScholarPubMed
Welschmeyer, A, Berke, GS. An updated review of the epidemiological factors associated with recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol 2021;6:226–33CrossRefGoogle ScholarPubMed
Tjon Pian Gi, REA, San Giorgi, MRM, Slagter-Menkema, L, van Hemel, BM, van der Laan, BFAM, van den Heuvel, ER et al. Clinical course of recurrent respiratory papillomatosis: comparison between aggressiveness of human papillomavirus-6 and human papillomavirus-11. Head Neck 2015;37:1625–32CrossRefGoogle ScholarPubMed
Buchinsky, FJ, Valentino, WL, Ruszkay, N, Powell, E, Derkay, CS, Seedat, RY et al. Age at diagnosis, but not HPV type, is strongly associated with clinical course in recurrent respiratory papillomatosis. PLoS One 2019;14:e0216697CrossRefGoogle Scholar
Rombaldi, RL, Serafini, EP, Mandelli, J, Zimmermann, E, Losquiavo, KP. Transplacental transmission of human papillomavirus. Virol J 2008;5:106CrossRefGoogle ScholarPubMed
Silverberg, MJ, Thorsen, P, Lindeberg, H, Grant, LA, Shah, KV. Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis. Obstet Gynecol 2003;101:645–52Google ScholarPubMed
Kashima, HK, Shah, F, Lyles, A, Glackin, R, Muhammad, N, Turner, L et al. A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope 1992;102:9–13CrossRefGoogle ScholarPubMed
Ruiz, R, Achlatis, S, Verma, A, Born, H, Kapadia, F, Fang, Y et al. Risk factors for adult-onset recurrent respiratory papillomatosis. Laryngoscope 2014;124:2338–44CrossRefGoogle ScholarPubMed
Rasmussen, ER, Schnack, DT, Jørkov, AS, Raja, AA, Olsen, CH, Homøe, P. Long-term follow-up and outcome in patients with recurrent respiratory laryngeal papillomatosis. Dan Med J 2017;64:A5424Google ScholarPubMed
Armstrong, LR, Derkay, CS, Reeves, WC. Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. RRP task force. Arch Otolaryngol Head Neck Surg 1999;125:743–8CrossRefGoogle Scholar
Reeves, WC, Ruparelia, SS, Swanson, KI, Derkay, CS, Marcus, A, Unger, ER. National registry for juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 2003;129:976–82CrossRefGoogle Scholar
Hess, MM, Fleischer, S, Ernstberger, M. New 445 nm blue laser for laryngeal surgery combines photoangiolytic and cutting properties. Eur Arch Otorhinolaryngol 2018;275:1557–67CrossRefGoogle Scholar
Hamdan, AL, Ghanem, A. Un-sedated office-based application of blue laser in vocal fold lesions. J Voice 2023;37:785–9CrossRefGoogle ScholarPubMed
Hock, K, Kennedy, A, Howell, R, Friedman, A, de Alarcon, A, Khosla, S. Surgery and adjuvant therapy improve Derkay scores in adult and pediatric respiratory papillomatosis. Laryngoscope 2022;132:2420–6CrossRefGoogle ScholarPubMed
Preuss, SF, Klussmann, JP, Jungehulsing, M, Eckel, HE, Guntinas-Lichius, O, Damm, M. Long-term results of surgical treatment for recurrent respiratory papillomatosis. Acta Otolaryngol 2007;127:1196–201CrossRefGoogle ScholarPubMed
Northern Medical Physics and Clinical Engineering. Airway Intervention Registry: Recurrent Respiratory Papillomatosis (AIR: RRP). In: https://rrp.org.uk/results/ [3 December 2023]Google Scholar
Liu, S, Wang, J, Shao, J. Safety of different surgical modalities for recurrent respiratory papillomatosis resection: a systematic review and meta-analysis. Clin Otolaryngol 2023;48:403–13CrossRefGoogle ScholarPubMed
Hu, D, Goldie, S. The economic burden of noncervical human papillomavirus disease in the United States. Am J Obstet Gynecol 2008;198:500.e1-7CrossRefGoogle ScholarPubMed
Bishai, D, Kashima, H, Shah, K. The cost of juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 2000;126:935–9CrossRefGoogle ScholarPubMed
Tam, S, Wu, CF, Peng, HL, Dahlstrom, KR, Sturgis, EM, Lairson, DR. Cost of treating recurrent respiratory papillomavirus in commercially insured and Medicaid patients. Laryngoscope 2020;130:1186–94CrossRefGoogle ScholarPubMed
Harrison, A, Montgomery, J, Macgregor, FB. Economic impact of recurrent respiratory papillomas in a UK adult population. J Laryngol Otol 2016;130:645–9CrossRefGoogle Scholar
So, RJ, McClellan, K, Best, SR. Recurrent respiratory papillomatosis: quality of life data from an international patient registry. Laryngoscope 2023;133:1919–26CrossRefGoogle ScholarPubMed
Karatayli-Ozgursoy, S, Bishop, JA, Hillel, A, Akst, L, Best, SRA. Risk factors for dysplasia in recurrent respiratory papillomatosis in an adult and pediatric population. Ann Otol Rhinol Laryngol 2016;125:235–41CrossRefGoogle Scholar
Majoros, M, Devine, KD, Parkhill, EM. Malignant transformation of benign laryngeal papillomas in children after radiation therapy. Surg Clin North Am 1963;43:1049–61CrossRefGoogle ScholarPubMed
Donne, AJ, Hampson, L, Homer, JJ, Hampson, IN. The role of HPV type in recurrent respiratory papillomatosis. Int J Pediatr Otorhinolaryngol 2010;74:7–14CrossRefGoogle ScholarPubMed
Zarod, AP, Rutherford, JD, Corbitt, G. Malignant progression of laryngeal papilloma associated with human papilloma virus type 6 (HPV-6) DNA. J Clin Pathol 1988;41:280–3CrossRefGoogle ScholarPubMed
Doyle, DJ, Henderson, LA, LeJeune, FE Jr, Miller, RH. Changes in human papillomavirus typing of recurrent respiratory papillomatosis progressing to malignant neoplasm. Arch Otolaryngol Head Neck Surg 1994;120:1273–6CrossRefGoogle Scholar
Fancello, V, Melis, A, Piana, AF, Castiglia, P, Cossu, A, Sotgiu, G et al. HPV Type 6 and 18 coinfection in a case of adult-onset laryngeal papillomatosis: immunization with Gardasil. Case Rep Otolaryngol 2015;2015:916023Google Scholar
Alanazi, A, Karas, AF, Husain, IA. Recurrent respiratory papillomatosis: an update. Int J Head Neck Surg 2022;13:1CrossRefGoogle Scholar
Pai, SI, Wasserman, I, Ji, YD, Gilman, M, Hung, YP, Faquin, WC et al. Pulmonary manifestations of chronic HPV infection in patients with recurrent respiratory papillomatosis. Lancet Respir Med 2022;10:997–1008CrossRefGoogle ScholarPubMed
Yang, Q, Li, Y, Ma, L, Xiao, Y, Wang, H, Ding, Y et al. Long-term outcomes of juvenile onset recurrent respiratory papillomatosis with pulmonary involvement. Laryngoscope 2021;131:EE2277–83CrossRefGoogle ScholarPubMed
Wierzbicka, M, Klussmann, JP, San Giorgi, MR, Wuerdemann, N, Dikkers, FG. Oral and laryngeal HPV infection: incidence, prevalence and risk factors, with special regard to concurrent infection in head, neck and genitals. Vaccine 2021;39:2344–50CrossRefGoogle ScholarPubMed
Schraff, S, Derkay, CS, Burke, BL, Lawson, LB. American Society of Pediatric Otolaryngology members’ experience with recurrent respiratory papillomatosis and the use of adjuvant therapy. Arch Otolaryngol Head Neck Surg 2004;130:1039–42CrossRefGoogle ScholarPubMed
Harper, DM, DeMars, LR. HPV vaccines – a review of the first decade. Gynecol Oncol 2017;146:196–204CrossRefGoogle ScholarPubMed
Benedict, JJ, Derkay, CS. Recurrent respiratory papillomatosis: a 2020 perspective. Laryngoscope Investig Otolaryngol 2021;6:340–45CrossRefGoogle ScholarPubMed
Novakovic, D, Cheng, ATL, Zurynski, Y, Booy, R, Walker, PJ, Berkowitz, R et al. A prospective study of the incidence of juvenile-onset recurrent respiratory papillomatosis after implementation of a national HPV vaccination program. J Infect Dis 2018;217:208–12Google ScholarPubMed
Patel, C, Brotherton, JML, Pillsbury, A, Jayasinghe, S, Donovan, B, Macartney, K et al. The impact of 10 years of human papillomavirus (HPV) vaccination in Australia: what additional disease burden will a nonavalent vaccine prevent? Euro Surveill 2018;23:1700737CrossRefGoogle Scholar
Diakite, I, Nguyen, S, Sabale, U, Pavelyev, A, Saxena, K, Tajik, AA et al. Public health impact and cost-effectiveness of switching from bivalent to nonavalent vaccine for human papillomavirus in Norway: incorporating the full health impact of all HPV-related diseases. J Med Econ 2023;26:1085–98CrossRefGoogle ScholarPubMed
Owusu-Edusei, K, Palmer, C, Ovcinnikova, O, Favato, G, Daniels, V. Assessing the health and economic outcomes of a 9-valent HPV vaccination program in the United Kingdom. J Health Econ Outcomes Res 2022;9:140–50CrossRefGoogle ScholarPubMed
Rosenberg, T, Philipsen, BB, Mehlum, CS, Dyrvig, AK, Wehberg, S, Chirilǎ, M et al. Therapeutic use of the human papillomavirus vaccine on recurrent respiratory papillomatosis: a systematic review and meta-analysis. J Infect Dis 2019;219:1016–25CrossRefGoogle ScholarPubMed
Goon, P, Sauzet, O, Schuermann, M, Oppel, F, Shao, SY, Scholtz, LU et al. Recurrent respiratory papillomatosis (RRP) – meta-analyses on the use of the HPV vaccine as adjuvant therapy. NPJ Vaccines 2023;8:49CrossRefGoogle ScholarPubMed
American Academy of Otolaryngology-Head and Neck Surgery. Position Statement: Recurrent Respiratory Papillomatosis and Gardasil Vaccination. In: https://www.entnet.org/resource/position-statement-recurrent-respiratory-papillomatosis-and-gardasil-vaccination/ [14 April 2024]Google Scholar
Centers for Disease Control and Prevention. Supplemental information and guidance for vaccination providers regarding use of 9-valent HPV. In: https://www.cdc.gov/hpv/downloads/9vhpv-guidance.pdf [14 April 2024]Google Scholar
Garland, SM, Cheung, TH, McNeill, S, Petersen, LK, Romaguera, J, Vazquez-Narvaez, J et al. Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine. Vaccine 2015;33:6855–64CrossRefGoogle ScholarPubMed
Tjon Pian Gi, REA, Dietz, A, Djukic, V, Eckel, HE, Friedrich, G, Golusinski, W et al. Treatment of recurrent respiratory papillomatosis and adverse reactions following off-label use of cidofovir (Vistide®). Eur Arch Otorhinolaryngol 2011;269:361–2CrossRefGoogle ScholarPubMed
Derkay, CS, Volsky, PG, Rosen, CA, Pransky, SM, McMurray, JS, Chadha, NK et al. Current use of intralesional cidofovir for recurrent respiratory papillomatosis. Laryngoscope 2013;123:705–12CrossRefGoogle ScholarPubMed
Chadha, NK, James, A. Adjuvant antiviral therapy for recurrent respiratory papillomatosis. Cochrane Database Syst Rev 2012;(12):CD005053CrossRefGoogle ScholarPubMed
McMurray, JS, Connor, N, Ford, CN. Cidofovir efficacy in recurrent respiratory papillomatosis: a randomized, double-blind, placebo-controlled study. Ann Otol Rhinol Laryngol 2008;117:477–83CrossRefGoogle ScholarPubMed
Gazia, F, Galletti, B, Freni, F, Bruno, R, Sireci, F, Galletti, C et al. Use of intralesional cidofovir in the recurrent respiratory papillomatosis: a review of the literature. Eur Rev Med Pharmacol Sci 2020;24:956–62Google ScholarPubMed
Connor, MP, Brown, A, Palazzolo, M, Kunkel, J, Eller, R et al. Effect of vocal fold injection of cidofovir and bevacizumab in a porcine model. JAMA Otolaryngol Head Neck Surg 2014;140:155–9CrossRefGoogle ScholarPubMed
Chhetri, DK, Jahan-Parwar, B, Hart, SD, Bhuta, SM, Berke, GS, Shapiro, NL. Local and systemic effects of intralaryngeal injection of cidofovir in a canine model. Laryngoscope 2003;113:1922–6CrossRefGoogle Scholar
Lalezari, JP, Stagg, RJ, Kuppermann, BD, Holland, GN, Kramer, F, Ives, DV et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial. Ann Intern Med 1997;126:257–63Google ScholarPubMed
Broekema, FI, Dikkers, FG. Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol 2008;265:871–9CrossRefGoogle ScholarPubMed
Derkay, C, Multi-disciplinary Task Force on Recurrent Respiratory Papillomas. Cidofovir for recurrent respiratory papillomatosis (RRP): a re-assessment of risks. Int J Pediatr Otorhinolaryngol 2005;69:1465–7CrossRefGoogle ScholarPubMed
Wemer, RD, Lee, JH, Hoffman, HT, Robinson, RA, Smith, RJH. Case of progressive dysplasia concomitant with intralesional cidofovir administration for recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 2005;114:836–9CrossRefGoogle ScholarPubMed
Tjon Pian Gi, REA, Ilmarinen, T, van den Heuvel, ER, Aaltonen, LM, Andersen, J, Brunings, JW et al. Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients. Eur Arch Otorhinolaryngol 2013;270:1679–87CrossRefGoogle ScholarPubMed
Nagel, S, Busch, C, Blankenburg, T, Schütte, W. Treatment of respiratory papillomatosis – a case report on systemic treatment with bevacizumab [in German]. Pneumologie 2009;63:387–9CrossRefGoogle ScholarPubMed
Pogoda, L, Ziylan, F, Smeeing, DPJ, Dikkers, FG, Rinkel, RNPM. Bevacizumab as treatment option for recurrent respiratory papillomatosis: a systematic review. Eur Arch Otorhinolaryngol 2022;279:4229–40CrossRefGoogle ScholarPubMed
Ablanedo-Terrazas, Y, Estrada-Camacho, O, Alvarado-de la Barrera, C, Ramírez-García, A, Tona-Acedo, G, Bross-Soriano, D et al. Efficacy of cidofovir versus bevacizumab in recurrent respiratory papillomatosis: a randomized, double-blind, placebo-controlled pilot study. Acta Otorrinolaringol Esp (Engl Ed) 2021;73:82–8CrossRefGoogle Scholar
Sidell, DR, Balakrishnan, K, Best, SR, Zur, K, Buckingham, J, De Alarcon, A et al. Systemic bevacizumab for treatment of respiratory papillomatosis: international consensus statement. Laryngoscope 2021;131:E1941–9CrossRefGoogle ScholarPubMed
Fernandez-Bussy, S, Labarca, G, Vial, MR, Soto, R, Mehta, HJ, Jantz, M et al. Recurrent respiratory papillomatosis and bevacizumab treatment. Am J Respir Crit Care Med 2018;197:539–41CrossRefGoogle ScholarPubMed
Bai, K, Allen, C. How enhancing immunity to low-risk HPV could cure recurrent respiratory papillomatosis. Laryngoscope 2021;131:2041–7CrossRefGoogle ScholarPubMed
Sardesai, NY, Weiner, DB. Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immunol 2011;23:421–9CrossRefGoogle ScholarPubMed
Aggarwal, C, Cohen, RB, Morrow, MP, Kraynyak, KA, Sylvester, AJ, Cheung, J et al. Immune therapy targeting E6/E7 oncogenes of human papillomavirus type 6 (HPV-6) reduces or eliminates the need for surgical intervention in the treatment of HPV-6 associated recurrent respiratory papillomatosis. Vaccines (Basel) 2020;8:56CrossRefGoogle ScholarPubMed
Mau, T, Amin, MR, Belafsky, PC, Best, SR, Friedman, AD, Klein, AM et al. Interim results of a phase 1/2 open-label study of INO-3107 for HPV-6 and/or HPV-11-associated recurrent respiratory papillomatosis. Laryngoscope 2023;133:3087–93CrossRefGoogle ScholarPubMed
INOVIO Pharmaceuticals News Release, January 03 2024: INOVIO Plans to Submit a BLA for INO-3107 as a Potential Treatment for RRP in Second Half of 2024 Under Accelerated Approval Program. In: https://ir.inovio.com/news-releases/news-releases-details/2024/INOVIO-Plans-to-Submit-a-BLA-for-INO-3107-as-a-Potential-Treatment-for-RRP-in-Second-Half-of-2024-Under-Accelerated-Approval-Program/default.aspx#:~:text=%22Our%20plan%20is%20to%20complete,INO%2D3107%20in%202025.%22 [24 January 2024]Google Scholar
Lee, MY, Metenou, S, Brough, DE, Sabzevari, H, Bai, K, Jochems, C et al. Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis. NPJ Vaccines 2021;6:86CrossRefGoogle ScholarPubMed
National Library of Medicine, Clinical Trials database. In: https://www.clinicaltrials.gov/study/NCT04724980 [24 January 2024]Google Scholar
Kwok, G, Yau, TCC, Chiu, JW, Tse, E, Kwong, YL. Pembrolizumab (Keytruda). Hum Vaccin Immunother 2016;12:2777–89CrossRefGoogle ScholarPubMed
Pai, SI, Friedman, AD, Franco, R, Muniappan, A, Park, JC, Campbell, NP et al. A phase II study of pembrolizumab for HPV-associated papilloma patients with laryngeal, tracheal, and/or pulmonary involvement. J Clin Oncol 2019;37:2502 [abstract: 2019 ASCO Annual Meeting]CrossRefGoogle Scholar
Wangu, Z, Hsu, KK. Impact of HPV vaccination on anogenital warts and respiratory papillomatosis. Hum Vaccin Immunother 2016;12:1357–62CrossRefGoogle ScholarPubMed
Bevacizumab (Monograph). https://www.nice.org.uk/guidance/ta214/chapter/2-The-technology [3 December 2023]Google Scholar