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Dermatology

Cite as: Archiv EuroMedica. 2026. 16; 2. DOI 10.35630/2026/16/Iss.2.20

Received 5 February 2026;
Accepted 24 April 2026;
Published 30 April 2026

Benign HPV Warts of the Head and Neck: What current evidence supports for treatment

Iga Poprawa , Michał Stermach¹ ,
Nina Kubikowska¹ , Zuzanna Gąsior² ,
Przemek Krukowski² , Małgorzata Landowska¹ ,
Agata Leszek⁴ , Anna Motybel¹ ,
Wiktoria Janik³ , Zuzanna Lecyk¹

¹ Medical University of Warsaw, Poland
²Tytus Chałubiński District Hospital in Zakopane, Poland
³Medical University of Silesia, Katowice, Poland
⁴4th Military Clinical Hospital in Wroclaw, Poland

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   iga.poprawa@gmail.com

ABSTRACT

Background

Benign HPV-related warts of the head and neck are common lesions in children, adolescents, and young adults. Despite their non-malignant nature, their visibility, persistence, and recurrence result in a significant cosmetic and psychosocial burden. Management in this anatomically sensitive region requires balancing clinical effectiveness with preservation of cosmetic outcomes. Available evidence is heterogeneous and frequently not specific to the head and neck, as many studies combine different anatomical sites and lesion types.

Aims

To critically evaluate current treatment options for benign HPV-induced warts of the head and neck, with emphasis on the balance between clinical effectiveness and cosmetic safety, and to compare minimally invasive and destructive approaches in terms of recurrence, safety, and cosmetic outcomes.

Methods

A narrative review with a structured literature search was conducted using PubMed, PubMed Central, and Google Scholar. ResearchGate was used as an additional source. The search covered publications from 2015 to November 2026 and was limited to English-language studies. Eligible publications included meta-analyses, systematic reviews, randomized controlled trials, observational studies, and clinical guidelines. Study selection and data extraction were performed by two reviewers. A total of 42 studies were included in the qualitative synthesis.

Results

No single treatment modality was identified as universally superior. Destructive methods demonstrate high clearance rates but are associated with a higher risk of pain, scarring, pigmentary changes, and recurrence, which limits their use in cosmetically sensitive areas. Minimally invasive approaches, particularly laser-based therapies, show high effectiveness, with reported clearance rates of approximately 70 to 90 percent, and more favorable cosmetic outcomes. Intralesional immunotherapy demonstrates variable effectiveness, ranging from 23 to 95 percent, reflecting differences in agents, treatment protocols, and study populations, and may enable clearance of both treated and distant lesions with minimal risk of scarring. Topical and systemic therapies show moderate effectiveness but require prolonged treatment and high patient adherence. Evidence on HPV vaccination suggests a possible therapeutic effect, although current data remain limited and heterogeneous.

Conclusions

Management of benign HPV warts of the head and neck requires an individualized approach. In relation to the research questions, minimally invasive methods and immunotherapy, in selected clinical contexts, may provide a more favorable balance between effectiveness and cosmetic safety compared to destructive approaches, while destructive methods remain appropriate in selected cases. The lack of head-and-neck-specific data, heterogeneity of study designs, and limited long-term follow-up restrict the strength of conclusions and do not allow the development of standardized treatment algorithms. Further high-quality studies with standardized outcomes are required.

Keywords: human papillomavirus, head and neck warts, benign HPV lesions, minimally invasive therapy, immunotherapy, laser therapy, recurrence, cosmetic outcomes

INTRODUCTION

Benign human papillomavirus infection of the head and neck manifests as a spectrum of epithelial proliferative lesions, most commonly verruca plana and verruca vulgaris, affecting predominantly children, adolescents, and young adults. Despite their non malignant nature, these lesions represent a clinically significant problem due to their visibility, persistence, and tendency to recur, leading to considerable psychosocial burden and reduced quality of life [1],[8],[15].

HPV demonstrates a marked tropism for stratified squamous epithelium of the skin and mucosa, and low risk genotypes are responsible for the development of benign lesions in the oral cavity and facial region [9],[10]. Although malignant transformation in common cutaneous warts is rare, their clinical relevance is determined by functional discomfort, aesthetic impact, and the need for repeated interventions [14],[16]. In many cases, especially in pediatric populations, spontaneous regression may occur, but persistent or cosmetically disturbing lesions require active management [15],[16].

Therapeutic decision making in the head and neck region is particularly complex. Standard destructive approaches such as cryotherapy, electrosurgery, and chemical cautery are associated with high clearance rates but also with pain, scarring, and pigmentary disturbances, which significantly limit their use in visible areas [22],[23]. As a result, current clinical practice increasingly favors minimally invasive and tissue-sparing strategies that aim to preserve skin integrity while maintaining therapeutic efficacy [1],[2],[3].

Laser-based techniques, including Nd:YAG, Er:YAG, and pulsed dye lasers, have demonstrated high effectiveness with favorable cosmetic outcomes and low recurrence rates in multiple studies, although their availability and cost may restrict widespread use [2],[3],[27]. Pharmacological approaches, including topical and systemic retinoids and immunomodulatory agents, represent safer alternatives with moderate efficacy, but require prolonged treatment and high patient adherence [29],[30].

In recent years, immunotherapeutic strategies have gained increasing attention. Intralesional immunotherapy using agents such as Candida antigen, MMR vaccine, or purified protein derivative stimulates cell mediated immune responses and may lead to clearance of both treated and distant lesions, making it particularly relevant for multiple and recalcitrant warts [4],[5],[32],[33]. In parallel, emerging evidence suggests a potential therapeutic role of prophylactic HPV vaccination, although current data remain limited and are derived mainly from small studies and observational reports [37],[39].

Despite the growing body of literature, available evidence remains heterogeneous and often not specific to the head and neck region. Many studies combine different anatomical sites, limiting the applicability of their conclusions to cosmetically sensitive areas. Moreover, long term outcomes, recurrence rates, and standardized measures of cosmetic results are insufficiently reported.

The relevance of this topic is therefore determined by the high prevalence of benign HPV lesions, their psychosocial impact, and the lack of clearly defined, evidence based treatment algorithms tailored to the head and neck region.

OBJECTIVES

The aim of this review is to critically evaluate current therapeutic approaches for benign HPV induced warts of the head and neck, with emphasis on effectiveness, safety, cosmetic outcomes, and recurrence rates.

Research Questions

1. What treatment approaches provide the optimal balance between clinical effectiveness and cosmetic safety in the management of benign HPV warts of the head and neck?

2. How do minimally invasive methods compare with destructive techniques in terms of recurrence, safety, and cosmetic outcomes?

METHODOLOGY

A narrative review with a structured literature search was conducted to synthesize current evidence on the treatment of benign HPV induced warts of the head and neck.

The literature search was performed using PubMed, PubMed Central, and Google Scholar. ResearchGate was used as an additional source to identify relevant publications. The search covered publications from 2015 to November 2026. Only articles published in English were included.

The search strategy combined terms related to HPV, anatomical location, and treatment. In PubMed, the MeSH term “Papillomavirus Infections” was applied where appropriate. The following search queries were used:

1. "human papillomavirus" OR HPV AND (oral OR mucosal OR cutaneous OR facial OR "head and neck") AND (warts OR papilloma) AND (treatment OR therapy)
2. ("human papillomavirus" OR HPV) AND (warts OR papilloma OR "squamous papilloma" OR "focal epithelial hyperplasia" OR "oral verruca vulgaris") AND ("head and neck" OR head OR neck) AND (treatment OR therapy)
3. ("Papillomavirus Infections"[MeSH] OR HPV) AND (warts OR "squamous papilloma" OR "focal epithelial hyperplasia" OR "oral verruca vulgaris") AND ("head and neck" OR head OR neck)

Searches were conducted primarily within title and abstract fields where available.

Inclusion criteria comprised meta analyses, systematic reviews, randomized controlled trials, cohort studies, case control studies, and international or national clinical guidelines reporting on treatment and treatment effectiveness of benign HPV related lesions.

Exclusion criteria included studies not addressing the head and neck region, studies focused exclusively on malignant HPV related disease, non-clinical reports, and publications lacking data on treatment outcomes.

The search yielded a substantial number of records across the selected databases. After removal of duplicates and screening of titles and abstracts, potentially relevant articles were assessed in full text. A total of 42 studies met the predefined inclusion criteria and were included in the final qualitative synthesis.

Study selection and data extraction were performed independently by two reviewers. Discrepancies were resolved through discussion and consensus.

Data were qualitatively synthesized with emphasis on treatment effectiveness, safety profile, cosmetic outcomes, and recurrence rates. Given the heterogeneity of study designs and outcome measures, no quantitative meta-analysis was performed.

FINDINGS

Clinical and Biological background

Human papillomavirus (HPV) is an omnipresent double-stranded DNA virus that exhibits tropism for stratified squamous epithelium, which comprises the skin and mucosa. [(7)] Although HPV is widely recognized for its role in the pathogenesis of malignant changes, such as oropharyngeal and skin cancer, it also causes a wide spectrum of hyperproliferative benign lesions in different anatomical parts of the human body, including the head, neck, and oral cavity, which manifest in verruca vulgaris, squamous papilloma, oral condyloma acuminatum, and focal epithelial hyperplasia. [(8)] These changes are associated with particular low-risk HPV genotypes, such as HPV6, 11, 13, 32, 40, of which HPV11 is the most prominent type at oral sites, and HPV is the main cause of mucosal lesions[(9)], which are histologically characterized by exophytic growths with koilocytic changes reflecting viral cytopathic effect [(10)]. Even though these lesions are pathologically benign nature, they can have clinical and functional consequences, including discomfort, cosmetic concerns, and potential for recurrence [(11)].

Verruca vulgaris, known as the “common wart,” is typically induced by cutaneous HPV types, and although most prevalent on skin, it may rarely appear on the vermillion border or oral mucosa, presenting as hyperkeratotic exophytic plaques in a colour range pink to white, similar to their cutaneous counterpart. [(7),(12)]. Squamous papilloma is a benign, often solitary, pedunculated lesion with finger-like epithelial projections and is frequently associated with HPV-6 and HPV-11. They are most common in children[(12)]. Oral condyloma acuminatum is the most cauliflower-like of other papillomas, yet the rarest common intraorally [(12),(13)]. Focal epithelial hyperplasia (also known as Heck’s disease) is more often associated with a particular population rather than the general population due to human leukocyte antigen subtype HLA-DR4. [58] Its characteristics include multiple, nodular elevations of the oral mucosa. [(13)]

Indications for Treatment and Therapeutic Challenges

Most HPV-related skin warts on the face and neck are flat warts (verruca plana) or common warts and are benign, though they may cause major cosmetic and psychosocial burden, which is the most challenging reason for finding the most sustainable and the last harming method of treatment[(14),(15),(16)]. Malignant transformation in ordinary cutaneous warts is rare; risk rises mainly in special entities like epidermodysplasia verruciformis or strong immunosuppression. [(14),(17),(18)]. An acceptable approach to treatment not only involves immediate removal of lesions, but it is permissible to wait and watch the progress of the disease, because, as observed in the following researches, it is observed that in children, about two-thirds clear spontaneously within 2 years of occurring [(19),(16)]. For cosmetically sensitive areas for example face and neck, guidelines indicate treatment if lesions are numerous, persistent, symptomatic, or causing psychological distress, but consider a “wait and see” approach for small, recent, asymptomatic lesions [(18),(16)].

Recent approaches to the menagement of HPV-induced point out destructive methods, topical or systemic agents, and immunotherapies (including HPV vaccines), with no single modality universally superior across all wart types or patients [(20),(21)]. Recurrence and cosmetic outcomes are key determinants when comparing effectiveness. To avoid scarring and keratosis, preferred treatment methods should focus on non- or minimally destructive options for visible areas.

Destructive therapies such as electrosurgery, cryotherapy, and chemical cautery (e.g., trichloroacetic acid, TCA) are widely used for cutaneous warts. Electrosurgery demonstrates the highest cure rates (up to 100%) with lower recurrence (14.6% at 1 year) compared to TCA (94.1% cure, 27.6% recurrence), but is associated with more adverse effects, such as bleeding, scarring and pain [(22),(23),(24)]. Destructive therapies are generally avoided on the face due to cosmetic concerns [(1)].

Minimally invasive therapy, including laser, particularly Neodymium-doped Yttrium Aluminum Garnet (Nd: YAG), erbium YAG laser (Er:Yag)[(25)] and pulsed dye lasers, demonstrate high efficacy for facial and head/neck warts, with clearance rates often exceeding 70–90% and minimal recurrence [(20)], with excellent cosmetic outcomes and low risk of scarring [(1),(3),(2)]. Cosmetic outcomes are generally excellent, with low risk of scarring when performed by experienced practitioners [(1),(20),(26)]. Combined laser modalities (e.g., Er:YAG + Nd:YAG) may further improve clearance in recalcitrant cases [(25)]. This is because monochromic light energy in the wavelength of 1064 nm can destroy particular targeted tissue. [(27)] Photodynamic therapy and infrared coagulation are also effective, especially for recalcitrant cases, but access and cost may limit their use [(1),(2)]. Pulsed dye laser has the lowest adverse effect profile among laser types [(3)]. Used in specialized settings for cosmetically critical lesions that can be really effective, but cost and equipment limit its use [(1),(28),(16)].

Topical and Systemic Agents are common first line for common warts because they are safer and bring up better cosmetical effects than aggressive destruction[(19),(15)]. The limitation for that method is the requirement of weeks to months to first noticeable positive effects and adherence [(29)]. Retinoids (e.g., acitretin, isotretinoin) demonstrate efficacy in managing widespread or recalcitrant facial warts, providing favorable clinical outcomes, though side effects that may occur need for monitoring [(1),(30)]. Topical immunomodulators (eg. imiquimod) and agents like Candida antigen are also effective, especially for resistant lesions, but may cause local irritation. [(1),(3),(6)].

Intralesional immunotherapy (e.g., Candida antigen, MMR vaccine, PPD) is a non-destructive method and report mostly transient injection-site reactions and minimal scarring, even in cosmetically sensitive areas [(31),(32),(33)]. The efficACY REPORTED IN broader literature remains variable, ranging from 23% to 95% [33].

Destructive methods clear 65–85% of warts but have pain, scarring, dyspigmentation, and high recurrence; immunotherapy often clears injected and distant lesions and avoids scarring [(34),(4),(21)]. These approaches are tissue-sparing and can induce resolution of both treated and distant lesions, making them suitable for cosmetically sensitive areas.[(1),(4),(5),(6)]. Intralesional immunotherapy (eg. Candida antigen, MMR, PPD, PPD-based regimens) stimulate cell-mediated immunity against HPV, leading to clearance of both injected and distant warts, and are particularly useful for multiple or recalcitrant lesions [(5),(34),(4),(6)]. Currently, it is promising for multiple or recalcitrant warts, with clearance rates ranging from 23.3% to 95.2% in pediatric and adult populations [(4),(5),(6)]. More often used for multiple/recalcitrant extragenital warts; may clear distant lesions and spare tissue, but data are largely not site-specific to face/neck [(15),(16)]. Reported complete response rates for injected warts are: Candida antigen: ~39–88% [(5),(6)] MMR vaccine: ~26.5–92% [(5)], PPD: ~23.3–94.4% [(5),(4)]. PPD appears comparable to other immunotherapies with good safety, including in pregnancy, and is proposed as an alternative in high-tuberculosis-burden countries [(4)]. BCG gives lower clearance (~33–39.7%) [(5)]. Intralesional zinc and Candida antigen are inexpensive and technically simple options [(35),(6)]. Network meta-analysis (17 RCTs, mixed sites) found PPD and MMR among the best at reducing same-site recurrence versus other immunotherapies and cryotherapy [(36)]. Systematic reviews note high complete response with low short- to mid-term recurrence, but follow-up is typically up to 6 months; robust more than 12-month data and site-specific (facial) data are limited [(33),(32)].

Emerging evidence suggests that the quadrivalent and nonavalent HPV vaccines may induce regression of cutaneous warts, including facial lesions, particularly in children and young adults [(1),(37),(4)]. Systematic reviews report that prophylactic HPV vaccines (especially quadrivalent/nonavalent) can also induce regression of cutaneous and anogenital warts, with many case series describing complete remission, particularly with the three-dose quadrivalent vaccine [(37),(38),(39)]. However, the evidence is limited to case series and small studies, and the use is off-label [(37),(4)]. A focused systematic review on active anogenital warts found seven largely high-bias studies (1 RCT, 1 non-RCT, 3 case series, 2 case reports) showing partial and complete regression after systemic or intralesional vaccination, but evidence quality is low [(39)]. HPV vaccination should be offered to previously unvaccinated patients with AGW for preventive plus possible therapeutic benefit [(39),(37),(38)]. The role of intralesional HPV vaccine in already vaccinated patients is promising but still unclear and investigational [(1)]. Immunotherapeutic approaches, especially intralesional HPV vaccines whether, bivalent, quadrivalent, or nonavalent, show promising results for recalcitrant and multiple warts, with clearance rates ranging from 60–90% and low recurrence [(40),(41),(33),(42)]. Immunotherapy is particularly advantageous for patients with multiple or distant lesions, as it can induce systemic immune responses and clear untreated warts [(40),(33),(42)]. Cosmetic outcomes are excellent, with only minor injection-site reactions [(41),(33)].

The qualitative synthesis included various study types, primarily systematic reviews and meta-analyses. Table 1 summarizes the characteristics and main conclusions of the selected studies, highlighting their diverse geographical origins and sample sizes.

DISCUSSION

Benign HPV-related warts of the head and neck represent a clinical challenge requiring a balance between treatment effectiveness and preservation of cosmetic outcomes. In accordance with the research questions, the key issue is the comparison of therapeutic approaches based on two main parameters, clinical effectiveness and cosmetic safety.

Comparative analysis shows that destructive methods, including electrosurgery and cryotherapy, achieve high rates of lesion clearance. In some studies, cure rates reach 90–100 percent; however, these methods are associated with significant adverse effects, including pain, scarring, and pigmentary changes, and demonstrate higher recurrence rates in the long term [22,23]. This limits their use in anatomically and cosmetically sensitive areas of the head and neck.

Minimally invasive approaches, particularly laser-based therapies, demonstrate comparable effectiveness, with clearance rates in the range of 70–90 percent, while offering a more favorable cosmetic profile [1,2,3,20]. The incidence of scarring and persistent skin changes is lower, making these methods preferable for visible areas. However, availability of equipment and treatment costs remain important limiting factors [1,2].

Immunotherapy, particularly intralesional administration of antigens and vaccines, demonstrates a wide range of effectiveness, from 23 to 95 percent, reflecting substantial heterogeneity across studies [4,5,6,33]. This variability is associated with differences in the agents used, treatment protocols, patient characteristics, and study design. At the same time, this approach offers a distinct advantage by enabling clearance of both treated and distant lesions, with minimal risk of scarring [4,5,32,33]. This makes it particularly relevant for multiple and recurrent lesions.

Thus, minimally invasive methods and immunotherapy, in certain clinical contexts, provide a more favorable balance between effectiveness and cosmetic safety compared to destructive approaches, which directly addresses the first research question.

Comparison of minimally invasive and destructive methods indicates that, with comparable effectiveness, the advantage of minimally invasive approaches lies in a lower rate of complications and superior cosmetic outcomes. At the same time, destructive methods may be appropriate in cases of limited solitary lesions where rapid removal is required, provided that the patient is adequately informed.

A comparison of the clinical parameters for each treatment modality is presented in Table 2, which shows that destructive methods achieve high clearance, while laser and immunotherapeutic approaches yield better cosmetic results. It is shown that non-destructive methods have a better balance between recurrence and cosmetic outcome.

It should be emphasized that benign HPV-related lesions include both cutaneous and mucosal forms, which differ significantly in clinical behavior and therapeutic management [8,10]. Cutaneous lesions are more amenable to destructive and laser-based methods, whereas mucosal lesions require a more cautious approach due to the risk of functional impairment and tissue damage. However, most available studies combine these groups, which limits the ability to perform precise comparative analysis and reduces the applicability of findings to specific clinical scenarios.

Clinical applicability also depends on lesion characteristics. In solitary, localized lesions, destructive methods may be used to achieve rapid clinical clearance. In multiple or recurrent lesions, immunotherapy or combined approaches may be more appropriate, given their ability to modulate the immune response and reduce recurrence risk [4,5,33]. In pediatric populations, the potential for spontaneous regression should be considered, making a watchful waiting strategy appropriate in selected cases [15,16]. However, the available data do not allow the development of standardized treatment schemes or clear therapeutic algorithms for different patient groups.

Analysis of the literature reveals several important limitations. A substantial proportion of studies combine different anatomical sites, including the trunk and extremities, as well as cutaneous and mucosal lesions, which reduces the applicability of results to the head and neck region [1,15]. The duration of follow-up in most studies is limited to six months or less, which does not allow reliable assessment of recurrence [32,33]. In addition, studies are heterogeneous in design, outcome measures, and evaluation of cosmetic results, which complicates direct comparison.

Another important limitation is the lack of standardized quantitative outcome measures, which restricts accurate comparison of treatment effectiveness. The reported ranges of effectiveness reflect aggregated data and do not allow identification of a clearly superior therapeutic strategy.

Regarding HPV vaccination, available evidence is based primarily on small studies and case series with a high risk of bias [37,39]. Although regression of lesions has been observed, the level of evidence remains insufficient to support clinical recommendations.

Overall, interpretation of the available data indicates the need for individualized treatment decisions based on lesion characteristics and patient priorities, with preference given to approaches that achieve an optimal balance between effectiveness and cosmetic safety.

CONCLUSIONS

Benign HPV-induced warts of the head and neck are common lesions that, despite their non-malignant nature, often require treatment due to cosmetic visibility, persistence, recurrence, and associated psychosocial burden. Management in this anatomically and aesthetically sensitive region remains challenging, as therapeutic effectiveness must be balanced against the risk of scarring, dyspigmentation, and tissue damage.

Available evidence indicates that no single treatment modality is universally optimal. In relation to the first research question, current data suggest that minimally invasive approaches and immunotherapy, in selected clinical situations, may provide a more favorable balance between clinical effectiveness and cosmetic safety compared to destructive methods. However, this balance depends on lesion characteristics, number of lesions, and patient-specific factors.

In relation to the second research question, comparison of minimally invasive and destructive approaches shows that, while effectiveness may be comparable, minimally invasive methods are generally associated with a lower risk of adverse cosmetic outcomes. At the same time, destructive techniques remain effective options for selected cases, particularly for solitary lesions requiring rapid removal.

Therapeutic decisions should therefore be individualized, taking into account lesion morphology, extent, patient age, immune status, treatment tolerance, and cosmetic expectations. Laser-based therapies and intralesional immunotherapy represent important tissue-sparing options, particularly for visible, multiple, or recurrent lesions, while topical and systemic therapies may be useful in selected cases despite longer treatment duration and adherence requirements.

A key limitation of the available evidence is the frequent combination of different anatomical sites, including cutaneous and mucosal lesions from regions beyond the head and neck, which significantly reduces the applicability of findings to this specific anatomical area. In addition, the lack of standardized outcome measures and limited long-term follow-up further constrain interpretation of treatment effectiveness and recurrence.

Emerging evidence suggests a potential therapeutic role of prophylactic HPV vaccination, but current data remain limited, heterogeneous, and largely based on small studies with a high risk of bias. Its use in this context remains investigational.

Overall, management of benign HPV warts of the head and neck requires an individualized approach with careful consideration of both effectiveness and cosmetic outcomes. Further high-quality, head-and-neck-specific studies with standardized outcome measures and longer follow-up are needed to enable the development of more precise and evidence-based treatment strategies.

DISCLOSURE

Authors’ Contributions

All authors have read and agreed with the published version of the manuscript.

Use of Artificial Intelligence

The authors declare that no artificial intelligence tools were used in the generation, writing, editing, or revision of this manuscript. All content was created solely by the authors.

Funding

The article did not receive any funding.

Conflict of Interest

Authors declare no conflicts of interest.

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