Treatment of invasive neoplasms of the lower gastrointestinal tract, from the colon to the anus, exposes survivors to a high risk of post-treatment sexual dysfunction, making sexual health a vital part of survivorship care.1 This issue affects, and will continue to affect, an increasingly larger premenopausal Western female population, as the incidence of colorectal cancer (CRC)—the leading cause of post-treatment sexual dysfunction—is rising in adults under 50 years old.1,2
The trend has remained similar for at least thirty years for anal squamous cell carcinoma (ASCC), which is projected to cause 10,930 new cases and 2030 deaths in 2025, accounting for 0.5% of all new cancer cases, according to the US National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. The annual incidence, currently 2.0 per 100,000 men and women in the US, is increasing in developed societies (Figure 1), especially among women, with a 5-year survival rate of 84.5% for localized disease and 68.2% for regional disease, and with human papillomavirus (HPV) infection as the primary risk factor.1,3
Figure 1 ASCC yearly incidence and mortality in the USA Credit: National Cancer Institute – Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Anal Cancer. Copyright-free image. New cases from the dataset SEER 12 of the Surveillance, Epidemiology, and End Results (SEER) Program; deaths from official age-adjusted US mortality statistics, all races, both sexes.3.
Besides the psychological and body image distress, especially among younger women, the sequelae of treatment on sexual health vary. Sphincter-preserving pelvic radiotherapy, for example, can directly impair gonadal function, cause narrowing or shortening of the vagina (stenosis), and lead to anal sphincter dysfunction.1 Additionally, a consistent finding is a low desire that persists for years after cancer treatment, suggesting that women survivors may rarely expect a rebound in their sexual function and emphasizing the importance of psycho-educational support.1,4 To complicate matters further, particularly for younger women survivors, physicians may be inadequately trained to discuss sexual health issues after CRC and ASCC treatment despite their substantial impact on quality of life and self-esteem. The impact indeed appears significant: a literature review by the American Cancer Society from the mid-2010s found that 30–40% of women survivors who were sexually active before treatment became sexually inactive afterward.4 More recently, a high-level systematic review reported that sexual dysfunction affects up to 85% of ASCC survivors, with dyspareunia (17–65%), vaginal dryness and lack of vaginal lubrication (22–88%), and loss of libido (38–95%) being the most common symptoms.5
With these considerations in mind, addressing dyspareunia and vaginal dryness is crucial for improving quality of life and self-esteem in CRC and ASCC survivors, especially younger women who previously enjoyed a fulfilling sexual life before their cancer diagnosis. Over-the-counter products like lubricating gels and moisturizers might seem like straightforward solutions; however, using these products can interfere with foreplay, arousal, and the overall mood of intimacy, particularly due to the inevitable anxiety caused by the memory of pain during recent attempts. Additionally, these products only provide temporary relief during sexual activity.6
Addressing the dermal and submucosal atrophy of vulvar and vaginal tissues might be a more practical and rewarding long-term strategy, especially if anatomical issues like vaginal stenosis have not yet developed.
Energy-based fractional lasers and radiofrequency devices stimulate collagen contraction, neocollagenesis, and extracellular matrix production, activating fibroblasts and leading to improved tissue elasticity, increased blood flow, engorgement, and lubrication. However, the costs of specialized devices and handpieces, as well as the need for training, are significant drawbacks.7,8 Hyaluronic acid (HA) fillers provide a temporary solution thanks to their hydrating effect, resulting in an immediate boost in turgidity, elasticity, and tone; however, the benefits, while real, are often short-lived.9
A potential solution for women survivors of CRC and ASCC seeking to restore their intimate life after the traumatic experience of cancer is to combine the quick benefits of HA derivatives for vulvovaginal hydration with an ingredient that promotes long-term regeneration of the dermal and submucosal extracellular matrix, including collagen, elastin fibrils, and glycosaminoglycans. Extensively used in aesthetic medicine for skin rejuvenation, natural-origin Polynucleotides High Purification Technology, ideally combined with HA, may act as a solution after intradermal vulvar and submucosal vaginal injections.10,11
Polynucleotides High Purification Technology (PN HPT™)
PN HPT are highly fragmented polynucleotide residues, ranging from 50 to 2000 base pairs, free from biologically active contaminants and lacking direct pharmacological activity and allergic potential.10–12 Unlike the prescription active principle polydeoxyribonucleotide (PDRN), PN HPT are an ingredient of CE-marked, Class III medical devices.10 In addition to their short-term tissue-filling effect related to their hydrophilicity, PN HPT stimulates dermal fibroblasts to produce Type I collagen, elastin fibers, and extracellular matrix by passively restoring the dermal and submucosal pools of nitrogen bases and nucleotide precursors. These two properties of PN HPT act in synergy, as hydration of the extracellular matrix is an essential prerequisite for fibroblast vitality. Combining PN HPT with HA further enhances the vitality of fibroblasts, including in women’s intimacy.10–13
Materials and Methods
Baseline Clinical Situation
Between March and April 2025, a 42-year-old woman sought counsel from the Corresponding Author and her specialized center to address a severe vaginal dryness and dyspareunia that had developed over the past months. She had been referred by the University of Messina, Sicily, where, in March 2024, she had received a diagnosis of HPV-positive anal squamous cell carcinoma (ASCC), positive at immunohistochemistry for the p16 surrogate marker of HPV infection, and showing increased expression of the squamous differentiation marker p40.
The baseline images of the vulva and introitus taken by the corresponding Author at early visits on March 31 and April 9, 2025, showed menopausal hypotrophy and severe dryness (Figure 2). During both visits, clinical symptoms, assessed using an impromptu Likert-like scale (score range, 0–10), revealed a genitourinary syndrome of menopause (GSM) heavily skewed toward severe sexual dysfunction (vaginal dryness/lack of lubrication and dyspareunia: scores of 10 out of 10 for both). There were also moderately severe irritative symptoms, including soreness, tenderness, and tingling (score of 7 out of 10), along with itching and irritation (scores of 3 out of 10 for both), as well as vaginal discharge (score of 3 out of 10 with no tendency to stain undergarments). No urgency, dysuria, or recurrent urinary infections were observed. The sexual and gynecological anamnesis was uneventful: the woman had had a long-term companion for many years with a regular and gratifying monogamous sexual life, at least before the recent difficulties and dyspareunia associated with her precocious iatrogenic menopause. The couple had no wish for children and had practiced long-term estrogen-progestin and barrier contraception for several years. The woman could not remember well and was reticent to describe the events in her youth leading to her HPV infection, but many years had elapsed. She also reported no previous hormonal therapy.
Figure 2 Severe baseline picture of labia hypoplasia and dehydration of vulva and introitus on March 31, 2025 ((A) Baseline evaluation and first treatment session) and April 9 ((B) Second treatment session).
Imaging and Radiochemotherapy
In mid-February, an upfront abdominal magnetic resonance imaging (MRI) for metastatic workup with contrast at the University of Messina had revealed a neoplastic spread that extended to the sphincter muscle layer and satellite lymph nodes (staging: T3N1M0). Pharmacogenetic analysis was negative for dihydropyrimidine dehydrogenase (DPYD) and UDP-glucuronosyltransferase (UGT) polymorphisms.
Radiochemotherapy commenced in late March, with the woman in good clinical condition: ECOG Performance Status 0, hemoglobin at 12 g/dL, white blood cells at 11,870/mm3 with 70% neutrophils, platelets at 294,000/mm3, negative viral hepatitis B and C markers, and positive HbsAg following previous vaccination. The first treatment consisted of cisplatin (60 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 daily from days 1 to 4), administered through continuous infusion over 96 hours every four weeks. The second and final cycle, administered as planned on April 29, 2025, without delays due to adverse effects, included mitomycin (15 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 daily from days 1 to 5) through continuous infusion over 96 hours every four weeks, with concurrent radiotherapy on the same day. Besides her two chemotherapy cycles, the woman completed 33 radiotherapy sessions by late May (total dose: 6040 cGy). During treatment, the woman assumed some nutritional supplements, including vitamins, but nothing systematic or high-dose.
Compared to the mid-February upfront abdominal MRI, the neoformation in the anal canal appeared significantly smaller at a new upfront abdominal MRI in early July 2024, with only a little residual heteroplastic neoformation still infiltrating the wall (dimensions: 19X20X23 mm) and partially extending into the lumen. The intense uptake of the glucose metabolism tracer in the rectal region (first positron emission tomography in early March 2024) had disappeared by late August, leaving only some modest, non-specific residual tracer uptake in the anorectal region, and no persisting uptake in regional lymph nodes and the mesorectal and presacral regions. The last December 2024 upfront MRI showed no residual pathological tissue within the resolution power of the procedure (5 mm).
A gynecological exam in July 2024 showed an anteverted uterus with mild fibrosclerosis and typical menopausal changes attributed to radiochemotherapy, including atrophic labia, vaginal and uterine atrophy, and scleroatrophic ovaries. In May 2025, a follow-up gynecological examination revealed improvement in all atrophic signs and progression of ovarian scleroatrophy.
Management of Vaginal Dryness and Dyspareunia
The chosen approach was to combine hydration of vulvovaginal tissues with HA to provide immediate relief from dryness, while promoting long-term deep regeneration of the atrophic vulvar dermis and vaginal submucosa. The CE-marked, Class III NEWGyn® medical device, designed for intradermal and submucosal injections, enabled this dual strategy. NEWGyn® (Mastelli Srl, Sanremo, Italy) is an isotonic, viscoelastic, pyrogen-free, sterile gel containing 10 mg/mL of PN HPT, 10 mg/mL of HA, and 220 micromoles per mL of mannitol as an inhibitor of enzymatic and oxidative HA degradation in a single-use 2-mL Luer-Lock® prefilled glass syringe with two 30G/13 mm needles (18-mm needle beyond the hymenal ring).
Following an initial overall assessment, a microinvasive treatment plan was proposed, and a signed informed consent form was obtained for publication of the case details and any accompanying images. A subsection in the informed consent form permitted the publication or presentation at congresses and educational meetings of iconographic materials for scientific and educational purposes. The first PN HPT treatment session followed on March 31, 2025. The mutually agreed-upon treatment plan consisted of six injection sessions, administered at intervals of 1.5 to 4 weeks. The second treatment session was scheduled for April 9, 2025. A galenic anesthetic cream (30% lidocaine gel prepared by a local pharmacy) was applied to the vulvar areas 30 minutes before the procedure. Figure 3 shows the distribution of the intradermal injection points on the labia majora; some additional infiltrations were carefully performed in the superficial submucosal layer of the introitus and beyond the hymenal ring. In the vulvar area, infiltrations were performed linearly and retrogradely, starting below the posterior labial commissure over the perineal body, continuing with the anterior labial commissure below the mons pubis, and ending with small hives on the labia minora at the side of the vestibule up to the prepuce.
Figure 3 Vulvar infiltration points on labia majora and labia minora (red circles) and progression of the successive vulvar injections. Evidence of the hymenal ring; intravaginal injections (not evidenced) beyond it. Reproduced from Palmieri IP et al (Ref. 13) under the terms of a Creative Commons CC BY-NC 4.0 License.
Results
Evolution of Vaginal Dryness and Dyspareunia After Baseline
Following the previously described baseline clinical evaluation, the third PN HPT/HA treatment session on May 6, 2025, roughly six weeks after the initial treatment, showed some progress in the objective vulvar situation (Figure 4), with improved spontaneous hydration of the labia and introitus (score of 9 out of 10). However, there was still no improvement in sexual dysfunction (dyspareunia score of 10 out of 10). The labia majora appeared somewhat less hypoplastic, with some improvements in all irritative symptoms: soreness, tenderness, and tingling (score of 6 out of 10), as well as itching and irritation (scores of 2 out of 10 for both), with no vaginal discharge.
Figure 4 Initial spontaneous correction of the vulvar and introitus dehydration on May 6, 2025, after approximately six weeks from the first PN HPT/HA injection session.
The objective vulvar picture showed little change after the fourth injection session, two weeks later (May 20, 2025), approximately seven and a half weeks from baseline assessment and the first PN HPT/HA injection session. Subjectively, the woman reported a notable improvement in vaginal dryness and lubrication (score of 6 out of 10), along with initial relief from her sexual dysfunction (dyspareunia score of 9 out of 10). She also noted a notable reduction in soreness, tenderness, and tingling (score of 4 out of 10), with tingling completely resolved. Additionally, the hypoplasia of the labia majora appeared to have improved.
Vaginal dryness and lubrication (score of 4 out of 10) and dyspareunia (score of 8 out of 10) further improved at the fifth infiltration session on June 6, 2015 (Figure 5), approximately two more weeks after the previous treatment session, with no additional changes in other subjectively reported GSM symptoms or the objective vulvar condition.
Figure 5 Overall lack of further improvements in the vulvar picture on June 6, 2025, after approximately ten weeks from the first PN HPT/HA injection session. The objective vulvar situation appears normal in line with the woman’s age.
At the sixth and final treatment session on June 25, 2025, approximately three weeks after the previous PN HPT/HA session and thirteen weeks after the first late-March infiltrative session, there were no residual subjective GSM symptoms, including soreness, tenderness, and tingling. Conversely, the sexual dysfunction showed a notable overall improvement: the vaginal dryness and lubrication score fell to 2 out of 10, and the dyspareunia score to 5 out of 10. The vulvar appearance was similar to that in the previous assessment and consistent with the expected picture for a 42-year-old woman. At the end of the treatment cycle, the woman reported reasonable satisfaction regarding safety (score of 8 out of 10) and subjective discomfort related to the procedure (score of 9 out of 10), as well as overall satisfaction with vulvar aesthetic results and the impact of menopausal symptoms and sexual life (score of 9 out of 10).
At a follow-up visit one month after the last treatment session (July 24, 2025), the objective vulvar condition appeared unchanged and generally normal for the age (Figure 6).
Figure 6 Unchanged objective vulvar picture at the one-month follow-up visit on July 24, 2025.
The woman reported no further subjective improvement in the existing low vaginal dryness and lubrication score (still 2 out of 10), but the dyspareunia score showed additional notable improvement (3 out of 10). She also reported a gratifying sexual life and a satisfactory couple relationship after an extended period. During that same visit, the woman and the investigator agreed on a maintenance session using the same device and the same dose of PN HPT/HA every six weeks.
Discussion
A significant proportion of patients treated for CRC and ASCC experience substantial late physical and psychological sequelae. The academic literature acknowledges a long neglect of sexual health.14 Even in recent times, and in supposedly advanced countries like Denmark, a recent study found that raising the issue of sexual problems often leads to rejection by healthcare professionals.15 Still, this issue significantly impacts the quality of life after treatments for CRC and ASCC aimed at a definitive cure. A recent longitudinal study of 97 women who completed treatment for CRC or ASCC showed that over 70% of the cohort was at risk of sexual dysfunction, with a median Female Sexual Function Index (FSFI) score of 21.8 among women less than one year from treatment completion (26.55 is the cutoff for differentiating women with and without sexual dysfunction),16 compared to an average of 30.8 in the control population.1
The hydrophilic PN HPT polymers spontaneously reorganize in tissues into a three-dimensional gel that absorbs water, providing a short-term volume-increasing effect.10–12 However, the main reason for exploring the PN HPT/HA option in the woman discussed in the case report was PN HPT’s long-term support of new collagen fiber deposition.10–12 Natural-origin PN HPT, with no toxicological risks at any dose or injection site, are more effective at stimulating collagen production than associated HA; however, the two ingredients work synergistically when combined.12,17, Of course, the information gleaned from this single case report has no more ambition than to be hypothesis-generating; future well-designed clinical and preclinical investigations, including dose-finding studies, are essential and unavoidable, although challenging to perform due to the low ASCC incidence.
Using an impromptu, non-validated, multi-domain Likert-like scale for follow-up evaluations of iatrogenic menopause symptoms can be considered a weak point of the case report. The authors empirically use such an impromptu scale in their everyday practice. Using a validated tool like FSFI would have been more scientifically sound; still, this single episodic experience suggests that the HPT/HA fixed combination discussed in the case report could be a viable option for treating GSM symptoms. This option may be especially relevant for the often severe sexual health issues secondary to iatrogenic menopause caused by chemoradiotherapy for CRC and ASCC. Restoring lost labial volumes with HA may quickly help restore the woman’s disrupted body self-image and emotional well-being, which can jeopardize intimacy and couple dynamics with partners. In this context, HA might even be considered as an immediate source of emotional support.
The improvement in vulvovaginal dryness and vulvar trophic appearance is delayed. Still, it then occurs quickly, starting with the fourth assessment and treatment session, which is seven and a half weeks after the baseline assessment and injection session. There were a few noticeable changes in vulvar aesthetic appearance in the following weeks. The woman reported a noticeable relief from previously unbearable discomfort and pain during intercourse around fifty days after the first injection session; she returned to an essentially normal and satisfying sexual life after about three months. The PN HPT ingredient, with its delayed but sustained support of fibroblast vitality and potential for skin and mucosal regeneration, is likely the primary factor behind the significant improvement in iatrogenic menopause symptoms, including neuropathic symptoms (tingling and soreness) and sexual issues. Previous studies support this hypothesis, showing the intense deposition of collagen and elastin fibers in the progressively regenerated vulvar dermis and vaginal submucosa exposed to PN HPT.10,11,13 Thanks to its sequential effects of HA and PN HPT, a prolonged treatment course with the PN HPT/HA combination—six injection sessions for the woman discussed in the case report—may be an effective way to address the often severe symptoms and sexual health issues of iatrogenic menopause in oncologic women patients.
Conclusions
In a woman undergoing chemoradiotherapy for locally advanced ASCC, a treatment lasting approximately thirteen weeks with a fixed combination of HPT, an ingredient known for its long-term regenerative properties on human connective tissues, and HA to address depleted volumes quickly, has effectively provided relief from severe neuropathic pain and restored a satisfying sexual life.
All activities performed by the Corresponding Author, the study investigator, were within the accepted regulatory indications for the ambulatory treatment with the discussed, approved natural polynucleotide-based medical devices, as stated in the Patient Information Leaflets. In accordance with the accepted regulatory requirements (ie, Articles 62 to 82 of the European Union Regulation MDR 2017/745 and Article 16 of Legislative Decree 137/2022), these considerations permit waiving any formal preliminary Institutional Review Board approval requirements. The authors are accountable for the clinical and editorial accuracy and integrity of the manuscript submitted to the International Journal of Women’s Health. The authors confirm that they have adhered to the journal’s ethical policies, as described in the guidelines for authors. The signed and dated informed consent statement form, which outlines the purpose, procedures, risks, and benefits, and alternative treatment strategies, and allows for the anonymous publication or presentation of all anonymous iconographic materials at congresses or educational meetings, is available upon request.
Data Sharing Statement
The minutes of the clinical activities during the preliminary assessment visit and the six treatment sessions are archived and available upon reasonable request from the Corresponding Author.
Acknowledgments
The authors acknowledge the contribution of Mastelli Srl, Sanremo, Italy, the holder of the Polynucleotides High Purification Technology and producer of the medical device used during the six treatment sessions, for supporting the publication costs. The authors also wish to thank the woman described in their case report for granting permission to reproduce her photographs in the manuscript.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Funding
The corporate sponsor will provide the only funding in the form of support for the Open Access article processing charges required by the International Journal of Women’s Health journal.
Disclosure
The authors declare that they have no conflict of interest. No author received funds or other benefits related to the clinical activities and the design of the case report manuscript; they have no paid or unpaid relationships with industry manufacturers, publishers, or other companies in any way connected to the submission.
Dr. Maria Pia Palmieri, the Corresponding Author, received research grants as a member of R&D steering boards, as a lecturer and tutor in continuous medical education activities, and as an investigator in clinical studies, including from Mastelli Srl, the manufacturer of the reviewed polynucleotide functional ingredient and medical device.
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