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Risks to consider in verrucae treatment; including needling.

According to recent systematic reviews of research in health care, there is a lack of high quality evidence for the efficacy of almost all verrucae treatments (Kwok et al, 2012) (1). However, Michelle Lipke (2006) (2), author of one review, emphasised that "lack of robust evidence of a therapy, which has not been subjected to [such] rigorous scientific testing, does not mean that it is not worth knowing about nor worthy of use in practice, particularly when a specific treatment has been utilised and reported, albeit anecdotally, with a reasonably high clinical success rate. The needling procedure, as first described by Falknor (3) in 1969, is such a therapy which has a growing body of evidence, including the publishing of controlled trials (Bower et al, 2014) (4) and discussion papers.

In April 2013, Dr Ivan Bristow (5) and I published an open access, patient-centred, review of clinical practice where the needling method for verrucae treatment was discussed and reported on in private practice. Expanding on the needling hypothesis, Dr Farina Hashmi presented her paper on auto-inoculation and Falknor'[s.sup.3] needling method for verruca pedis (Hashmi & Bristow, 2014) (6) at the Primary Care conference in 2014, which stimulated a great deal of interest and discussion. The pertinent comments made during the Question & Answer session highlight the importance of both patient and practitioner understanding the aetiology of HPV infection, their subtypes, as well as the risks and benefits of any verruca treatment that are already available to us.

Is it a verruca, or something else?

It goes without saying that, as with any treatment plan, correct diagnosis of any lesion is of paramount importance. If a practitioner is at all unsure of diagnosis or ifany lesion is worsening or not responding well to treatment we should always refer for further investigation in the form of dermoscopy or biopsy. A large portion of claims against practitioners for 'verrucae' treatment, with adverse events reported, is for the misdiagnosis of malignancy, i.e.; amelanotic melanoma, squamous cell carcinoma and nodular basal carcinoma, etc., can look remarkably similar to HPV lesions. To compound matters, there is also the very misleading term 'Verrucous Carcinoma' used for a squamous cell carcinoma, which is not usually associated with the Human Papilloma Virus (Wright et al, 2004) (7). 'Verrucous' is merely a pictorial expression for describing the appearance of the malignancy; i.e., verruca-looking.

Does needling present any danger of spreading malignancy?

As practitioners who frequently diagnose HPV lesions, we are obliged to understand and explain to our patients the relevance of HPV sub-types. This is imperative as many people wrongly associate HPV with malignancy. All warts on the body are of the Human Papilloma family. There are over 200 HPV types identified and amongst these there are approximately 40 genital HPV types. Amongst these are the HPV sub-types which are associated with malignant change. These high risk HPV sub-types are the lesions that have the DNA potential to become malignant, thus they are considered carcinogenic. These are; HPV-6, HPV-11, HPV-16, HPV-18, HPV31, HPV-33, HPV-45, HPV-52 and HPV-58. Lesions associated with the HPV sub-types 16 and 18 are the most prevalent types involved in the pathogenesis of anogenital (e.g., cervical) cancer, and HPV sub-types 6 and 11 cause genital warts and laryngeal papilloma. That said, most men and women with high risk HPV do not actually progress to cancer, as the body builds appropriate immunity to the acquired HPV sub-type (Frazer, 2009) (8).

To reiterate; High-risk HPV sub-types have been identified in cancers of the larynx, cervix, vagina, vulva, anus, and penis. Therefore, they are termed carcinogenic HPV. However, low-risk HPV sub-types are virtually never found in cancers. Therefore, they are termed non-carcinogenic.

Sub-types HPV-1, HPV-2 & HPV-4 are commonly associated with the hands and feet and seldom undergo malignant change. It's not impossible, but is very rare indeed because these sub-types can only replicate and survive in the epidermis, thus needling does not spread the virus. These benign HPV types utilise methods to positively avoid infection of deeper tissue (unlike the high risk alpha-PV types mentioned earlier, which infect genital mucosa) as this would induce an immune response to eradicate the virus.

Gross et al (1982) (9) & de Koning et al (2010) (10) described the benign HPV subtypes typically associated with hand warts and verrucae as;

HPV-1 (single). This sub-type is notoriously difficult to treat as it creates a huge amount of vacuolization, resulting in the rubbery, macerated texture and causes far more disturbance of cell differentiation throughout the entire thickness of the epidermis than HPV-2 & 4.

HPV-2 (mosaic). This sub-type produces some vacuolization in the Stratum Spinosum and Stratum Granulosum layers, leading to a honeycomb-like picture as it proliferates. This is probably the most superficial sub-type, so could explain a higher success rate with most treatment modalities.

HPV-4 (multiple) This sub-type causes a thicker Stratum Granulosum layer only, but results in a more compact Stratum Corneum layer.

DNA structure determines the HPV subtype and it is with this information that the recently available preventive vaccines for high risk types were formed; to target the specific sub-types HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52 and HPV-58. I'm sure that in the not-too-distant future, a vaccine will be developed using the same technology to target the benign sub-types associated with hand and foot warts. Until then, we can only utilise treatments that have been shown to both destroy HPV infected keratinocytes and induce an enhanced cell-mediated immune response to eradicate the virus.

Is HPV infection indicative of an Impaired Immune System?

Caution should always be exercised whilst discussing 'impaired immune systems' with patients who have HPV infection. Whilst it is acknowledged that immune-compromised patients are obviously more at risk of contracting and manifesting any viral infection, including HPV, we cannot and should not assume that the vice is versa. Moreover, we should be reassuring our patients that HPV infection is not indicative of an impaired immune system, as this clever virus has adapted ways to positively avoid a localised immune response in healthy, immune-competent patients.

There are a number of factors involved that contribute to the absence, or reduction, of a cellular immune response in immune-competent patients. Briefly they are;

* The epidermis is avascular.

* Latent virus particles in adjacent cells are not destroyed in keratolytic treatments (Bristow & Stiles, 2011) (11)

* HPV can alter Langerhan cell function and activate T suppressor cells (Frazer, 2009) (8)

* Virally infected cells have no surface markers (Bergot et al, 2011) (12)

Is needling verrucae unsafe?

As with any verrucae treatment modality, needling is not suitable for all patients. A full medical history should reveal any contraindications. Of course, the decision of whether to treat, or not, is incumbent on the practitioner according to ascertained risk. Thus, a patient presenting with peripheral vascular disease, diabetes mellitus, or any other underlying systemic condition which renders them high risk for delayed healing should be carefully considered for any verrucae treatment that creates a wound by tissue destruction; i.e. acids, cryotherapy, laser treatment or, indeed, needling. In high risk patients, the option of no treatment is often most suitable. If the lesion is painful then utilising conservative care by purely offloading any painful lesion and frequent sharp reduction of overlying callus may be the most appropriate treatment plan.

There is a plethora of literature detailing adverse events associated with caustic and freezing verrucae treatments, such as; sub-cutaneous tissue breakdown, abscess and deep seated infection, even amputation, yet practitioners continue to utilise the same treatment modalities. Why? Because current scientific evidence suggests that caustics are still deemed to be significantly efficacious and relatively safe if used appropriately and with caution, much like needling. Whilst this treatment is not a new modality and has been successfully utilised internationally for over 45 years, it is still undergoing further randomise controlled trials. Meanwhile, retrospective studies are continuing to suggest this is a safe and efficacious treatment.

In summary; If we have considered all the risks, i.e. correct diagnosis, the aetiology of HPV and suitability of the individual patient requesting verruca treatment then, in my professional opinion, needling is no more unsafe than any other verruca therapy. In fact, it could be argued that there is less tissue destruction as a more controlled wound is created than with caustics and freezing. This is, of course, part of ongoing research.... watch this space.

References:

(1.) Kwok CS, Gibbs S, Bennett C et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev 2012; 9ID001781

(2.) Lipke, M. An armamentarium of wart treatments. Clin. Med. Res. 2006, 4, 273-293Falknor GW: Needling-A new technique in verruca therapy. A case report. J Am Podiatr Med Assoc 1969, 59(2):51-52.

(3.) Falcnor GW: Needling-A new technique in verruca therapy. A case report. J Am Podiatr Med Assoc 1969, 59(2):51-52.

(4.) Cunningham DJ, Brimage JT, Naraghi RN & Bower VM. Needling Versus Liquid Nitrogen Cryotherapy for the Treatment of Pedal Warts J Am Podiatr Med Assoc 2014, 104(4) :394-401.

(5.) Longhurst B, Bristow IR : The Treatment of Verrucae Pedis Using Falknor's Needling Method: A Review of 46 Cases. Journal of Clinical Medicine. 2013; 2(2):13-21

(6.) Hashmi F; Bristow IR: Treating plantar warts: utilising natural immunity to induce wart regression Dermatological Nursing 2014, 13(1): 42-45

(7.) Wright PK, Vidyadharan R, Jose RM, Rao GS: Plantar verrucous carcinoma continues to be mistaken for verruca vulgaris. Plast Reconstr Surg. 2004 Mar; 113(3):1101-3.

(8.) Frazer IH: Interaction of human papillomaviruses with the host immune system: a well evolved relationship. Virology 2009, 384(2):410-414

(9.) Gross G, Pfister H, Hagedorn M, Gissmann L: Correlation between human papillomavirus (HPV) type and histology of warts. J Invest Dermatol. 1982 Feb; 78(2):160-4.

(10.) Maurits N. C. de Koning, Jan ter Schegget, Just A. H. Eekhof, Marga Kamp, Bernhard Kleter, Jacobijn Gussekloo, Mariet C. W. Feltkamp, Jan Nico Bouwes Bavinck, Karin J. Purdie, Christopher B. Bunker, Charlotte M. Proby, Rhonda Meys, Catherine A. Harwood, Wim G. V. Quint: Evaluation of a novel broad-spectrum PCR-multiplex genotyping assay for identification of cutaneous wart-associated human papillomavirus types.. J Clin. Microbiol. 2010, 48: 1706-1711.

(11.) Bristow IR, Stiles CJ: The treatment of stubborn plantar warts using topical 5% imiquimod cream Podiatry Now 2011, 14(10):14-16

(12.) Bergot A.-S., Kassianos A., Frazer I.H., Mittal D: New Approaches to Immunotherapy for HPV Associated Cancers. Cancers. 2011; 3(3):3461-3495.
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Author:Longhurst, Belinda
Publication:Podiatry Review
Date:Mar 1, 2016
Words:1733
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